tag:blogger.com,1999:blog-21351341534241938302024-02-20T19:33:31.493+11:00Concord Dependency SeminarsThis Web Page is for summaries of the 2 monthly Concord Dependency Seminars held in Western Sydney between 1999 and 2010. From January 2011 these seminars have transferred to Royal Prince Alfred Hospital and are convened by Dr Richard Hallinan and Prof Paul Haber.Unknownnoreply@blogger.comBlogger26125tag:blogger.com,1999:blog-2135134153424193830.post-16234752531810504872011-11-30T20:52:00.000+11:002011-11-30T20:54:51.483+11:00Final Concord seminar (ever): life beyond maintenance ..."The Exit Strategy Part 2: Is there life after methadone?" <br /><br />Tuesday December 7 2010 saw the final Dependency Seminar at Concord Hospital, which concluded with a presentation of native flowers and thanks to Andrew Byrne, whose energy and organizing skills whose energy and organizing skills kept the Concord Seminars going over more than a decade. The series continues in similar format and new venue, at Royal Prince Alfred Hospital. <br /><br />Nick Lintzeris and Richard Hallinan presented an overview of published evidence about duration of opioid substitution treatment (OST), withdrawal and reduction regimens, "cycling in and out of treatment", the relative ease of reductions for methadone and buprenorphine and other matters.<br /><br />Key points:<br /><br />People come off OST in numerous ways, the most common methods are simply jumping off, and gradual reductions.<br /><br />The issue of exit from OST should be discussed openly at the time of treatment induction. <br /><br />There should be a shared understanding of when coming off treatment is likely to be successful, and clear milestones for achieving this. <br /><br />Abstinence from problematic substance use, and psychosocial stability are generally preconditions for coming off OST.<br /><br />Psychoeducation is important to allay inappropriate fears about coming off treatment. <br /><br />Patients need to understand that their body takes time to adjust (reverse neuroadaption to opioids) - it's not just a matter of "the methadone getting out of my system”.<br /><br />A flexible menu of options for coming of treatment should be offered, as well as after care.<br /><br />There is no evidence that transfer from methadone to buprenorphine improves the chances of sustainably coming off OST, but it is one of the menu of options.<br /><br /><br /><br />Summary:<br /><br />A common complaint about opioid substitution treatment (OST) is that there is "no exit strategy". People talk of liquid handcuffs, and critics claim OST just keeps people addicted forever. <br /><br />How should the health professionals respond to a request for reductions toward abstinence? Is there any evidence to guide professional practice?<br /> <br />Richard Hallinan began by pointing out that people come off OST all the time, with retention rates varying from 40-70% after 12 months. Some "jump off" treatment, others use shorter or longer tapers of methadone or buprenorphine, or accelerated withdrawal regimens. But many or most of these people return to OST. There is a common pattern of cycling in and out of treatment, particularly with buprenorphine.<br /><br />RH proposed to discuss "exit" from OST in terms of coming off treatment "sustainably". In the absence of an agreed definition he proposed a working definition: “sustainable exit” means not needing to return to OST.<br /><br />Sadly, there is very little evidence for how this be best done. Korner and Waal (2005) reviewed the issue of reductions off MMT and found studies heterogenous, poorly described, methods and results extremely various. A total of 1900 people in 14 studies were followed up for 1 to 24 months after reductions off MMT, with reductions ranging over periods up to 7 months, with sustained periods of abstinence achieved by 33%, ranging from 22% to 86%. <br /><br />Interestingly the 86% figure comes from Andrew Byrne's 9-year follow up published in 2000. <br /><br />RH proposed some preconditions for sustainably coming off OST. There should be: <br />• no current injecting drug use nor problematic other substance use (otherwise there is a likelihood of relapse, or "swapping the witch for the bitch", ie substituting other drugs); <br />• no "chemical coping" with life stresses; <br />• psychosocial stability, including stable mental health (no uncontrolled mood or anxiety disorders) and stable housing; and <br />• no uncontrolled chronic pain.<br /><br />As to when to start reducing off OST, RH proposed there should usually be 3-6 months since last problematic opioid use, and since last injecting drug use. The journey of reductions doesn't really begin until you achieve a probationary period of abstinence. Every time a person in OST injects, they are resetting the "trip meter" on their journey. <br /><br />Should the reductions by a fixed or physician determined protocol, or flexible patient determined protocol with room to rest on the way? The small number of published benefit shows no clear benefit for physician regulation. <br /><br />How fast should reductions be? 10% per 3-4 days (as for example at the residential facility WHOS MTAR: see Concord Summary from 2005), or 10% per week, or per month? Senay et al (1977) randomised MMT patients to 3% or 10% weekly reductions, and those reducing by the slower protocol did clearly better on a number of measures.<br /><br />Should reductions be linear (straight down) or inverse exponential (landing like an aeroplane)? Strang and Gossop (1990) compared linear with inverse exponential reductions and found no benefit for the latter: perhaps because the reductions were completed within 10 days. One's impression is that most physicians and patients elect smaller dose reductions as their dose gets smaller. <br /><br />Many people describe having "hit a wall" during attempts at methadone reductions, often after 4 or 5 successful dose reductions, and actually increased their dose again after that.<br /><br />RH suggested one way of understanding the phenomenon of "hitting a wall" during reductions: consider the pattern of symptom recovery from one reduction, and then imagine what happens when you add more reductions. <br /><br />Previous studies from the Maudsley showed symptoms peaking at the very end of both 10 and 21 day methadone reductions protocols, and declining slowly (and apparently inverse exponentially!) after that, persisting in a long "tail" up to 40 days (Gossop et al 1987, 1989).<br /><br />Thus, after early rapid improvement of symptoms from one dose reduction, a person may be tempted to add another reduction, even though the "tail" of symptoms from the previous reduction persists. If enough "tails" accumulate, one is left with significant symptoms with no sign of improvement day to day: "hitting a wall".<br /><br />Patients need to understand that their body takes time to adjust (reverse neuroadaption to opioids) - it's not just a matter of "the methadone getting out of my system", as many people imagine.<br /><br />RH suggested reduction of 10% of the current dose (ie inverse exponential), every 3-4/weeks, resting whenever necessary, with the prescriber "pulling on the reins", as patients are often keen to reduce more quickly. <br /> <br />How long would it take to get off methadone at this rate? From 200mg methadone there are about 31 reductions. For example: 200mg - 180 - 165 - 150 - 135 - 120 - 110 - 100 - 90 - 80 - 70 - 62.5 - 55 - 50 - 45 - 40 - 35 - 32.5 - 30 - 27.5 - 25 - 22.5 - 20 - 17.5 - 15 - 12.5 - 10 - 8 - 6 - 4 - 2 - 0. <br /><br />At 3 weeks between reductions, that’s 93 weeks to come off 200mg. Compare that with reductions from 100mg (24 reductions = 72 weeks) or from 50mg (19 reductions = 57 weeks). <br /><br />The bottom end reductions take most of the time. <br /><br />To put that in perspective, RH referred to a study from The Redfern Clinic (Hallinan et al 2006) which found each 50mg of increased methadone dose doubled the odds of not using heroin, the same odds achieved by staying an extra 34 months on MMT at the same dose. <br /><br />Thus a higher dose may get people on the road to reductions much sooner, more than compensating for the modest increase in time required for reductions.<br /><br />Of course, at some point people have to jump off (otherwise the frog would never reach the wall). Some people jump at 10mg. One patient of the Byrne surgery continued on 1mg methadone/day for many months. <br /><br />Is coming off buprenorphine maintenance any easier? <br /><br />Although there is some evidence for the superiority of buprenorphine for opioid withdrawal management (Gowing et al 2009), there is no published evidence to demonstrate sustainable reductions off maintenance pharmacotherapy are easier or quicker with buprenorphine, nor any evidence that transfer from MMT to buprenorphine with subsequent reductions is more effective than reductions off methadone maintenance (though it is feasible: Breen et al 2003). Top end buprenorphine reductions may be particularly easy where the daily dose exceeds receptor saturation (typically above 16 mg/day). <br /><br />RH's advice is: don't transfer from methadone to buprenorphine for the sake of it; don't transfer to buprenorphine if methadone reductions are going well; but if the methadone dose is no longer "holding" 24 hours, there is a reasonable chance buprenorphine will last better. Methadone to buprenorphine transfer doesn't always succeed, and it can be disappointing to end up on 32mg buprenorphine when transferring from 25mg of methadone!<br /><br /><br />Nick Lintzeris advised us to take much of what RH had said with a grain of salt! <br /><br />People come off OST every which way, is the long and short of it. His rule of thumb is that 1/3 of people find coming off MMT easy and 1/3 find it very difficult. <br /><br />Breen et al (2003) found a majority of people on low dose methadone maintenance randomized to buprenorphine based reductions lasting up to 16 weeks managed to reduce to zero, but only 31% were abstinent from opiates a month later. The published evidence for long-term benefit of “rapid opioid detoxification” is equivocal at best (see seminar summary of The Exit Strategy Part 1).<br /><br />NL pointed out that although many people would like to come off OST, many are daunted by the prospect; as are their care providers. A large cross-sectional study of MMT clients found only 17% had interest, confidence and good prospects for methadone reductions. Clinic staff and doctors were less optimistic about post-withdrawal outcomes than patients. (Lenné et al 2001). <br /><br />NL also cited a recent study "Should I stay or should I go?" Coming off methadone and buprenorphine treatment. (Winstock et al 2010), showing high levels of interest and low levels of confidence in coming off OST; interest being higher in people who had been on treatment longer. Surprisingly, the most common method previously used was jumping off treatment (though perhaps that is why they were back in treatment). The idea of physician regulated-reductions was more popular among clients than patient-regulated. <br /><br />But it is true that we have little research to guide us. We were reminded of the historical context: the first days of MMT in which the opioid treatment was seen as replacement in a neurochemical deficiency syndrome, with the expectation that the treatment would be long term, followed by a swing toward low dose and limited duration treatment in the 1990s. As evidence showed inferior results for lower doses and shorter treatments, by the middle years of this decade the swing was back to higher doses and longer treatment. <br /><br />The fight to establish a person's right to stay on OST, if they need and want to, may have overshadowed considerations about how to end the treatment. It is particularly telling that one of the measures of treatment success in opioid pharmacotherapy is RETENTION in treatment. <br /><br />NL pointed out that little is known about the long term consequences of opioid pharmacotherapy on physical health, as the patient cohort ages: 16% of OST patients in Australia are over the age of 50, and as they grow older, there will be increasing problems with other medical illnesses, medication interactions, transport and mobility issues, and the cost of continuing supervised dosing.<br /><br />NL proposed that the issue of an exit from treatment should be discussed openly at the time of treatment induction. There should be a shared understanding of when coming off treatment is likely to be successful, and clear milestones for achieving this.P Psychoeducation is important to allay inappropriate fears about coming off treatment and a flexible menu of options for coming of treatment should be offered, as well as after care. Clearly we need more research on this subject.<br /><br /><br />There were two cases presented: <br /><br />Hugh, 47 yo, was already 20 years on MMT, and his last heroin many years ago, though he continued weekly to monthly cocaine use. His highest previous MMT dose was 170mg and current dose 110mg. Previous reductions had stalled at 80mg, several times. He had decided he would never be able to get his dose under 80mg. <br /><br />Detailed history revealed morning anxiety, butterflies in stomach especially when attending for supervised doses at 8am (take-home doses he consumed at 5am). Anxiety interfered with his work, sometimes feels afraid to go out. Hugh used occasional diazepam to assist with this, mainly on days of supervised dosing. On examination pre-dose Hugh had huge pupils and a pulse of 94. He was visibly anxious.<br /><br />Hugh was offered a trial of low dose fluvoxamine 25mg mane, increased to 50mg/day with considerable improvement in his anxiety. Advised that methadone reductions would fail while his cocaine use continued, he indeed ceased cocaine use. At time of writing his methadone dose had reached 15 mg by logarithmic reductions over 2 years. Reductions were supported by PRN dispensing of small numbers of diazepam tabs 5mg*4 at a time, though he has now ceased these.<br /><br />Discussion centred on the use of fluvoxamine to reduce methadone clearance in rapid metabolisers (with care needed that toxicity doesn't develop). One colleague reported a case of acute opioid withdrawal in a methadone patient who suddenly stopped their fluvoxamine.<br /><br />The second case was Domel, whose first MMT was at age 26. He was a heroin smoker of 8 years. Though he continued THC heavily, he ceased heroin quickly with methadone dose at 85mg and reduced to 35mg methadone by 1 year into treatment. He transferred to 16 mg buprenorphine, with further reductions to 4mg within 5 months, and to 1.2mg by 10 months. However further reductions were limited by restless and cramped legs when his dose was late, feeling nauseous in the morning before dose, unable to cope if he missed a day's dose. <br /><br />He reached 0.2 mg/day by 16 months, and 0.1mg (using "Temgesic" tablets) by 24 months into BMT. Despite the cost and inconvenience of continuing treatment, he was not prepared to jump off buprenorphine. At his physician's insistence he finally ceased buprenorphine a year later with assistance of clonidine, paracetamol, ibuprofen, leg and back stretches, and mirtazepine to assist with sleep. He remains opioid abstinent 12 months later. <br /><br />Discussion centred on the possibility that Domel's symptoms were psychological (which neither he nor his physician believed), the difficulty of low-end reductions, and the unavailability of buprenorphine/naloxone in tablets less than 2mg buprenorphine. <br /><br /><br /><br />Selected references<br /><br />Breen CL, Harris SJ, Lintzeris N, Mattick RP, Hawken L, Bell J, Ritter AJ, Lenné <br />M, Mendoza E. Cessation of methadone maintenance treatment using buprenorphine: transfer from methadone to buprenorphine and subsequent buprenorphine reductions. Drug Alcohol Depend. 2003 Jul 20;71(1):49-55.<br /><br />Byrne A. Nine-year follow-up of 86 consecutive patients treated with methadone in general practice, Sydney, Australia. Drug Alcohol Rev 2000;19:153 - 8.<br /><br />Gossop M, Bradley B, Phillips GT. An investigation of withdrawal symptoms shown by opiate addicts during and subsequent to a 21-day in-patient methadone detoxification procedure. Addict Behav. 1987;12(1):1-6.<br /><br />Gossop M, Griffiths P, Bradley B, Strang J. Opiate withdrawal symptoms in response to 10-day and 21-day methadone withdrawal programmes. Br J Psychiatry. 1989 Mar;154:360-3.<br /><br />Gowing L, Ali R, White JM. Buprenorphine for the management of opioid withdrawal. Cochrane Database Syst Rev. 2009 Jul 8;(3):CD002025. ..... "Buprenorphine may offer some advantages over methadone, at least in inpatient settings, in terms of quicker resolution of withdrawal symptoms and possibly slightly higher rates of completion of withdrawal."<br /><br />Hallinan R, Ray J, Byrne A, Agho K, Attia J. Therapeutic thresholds in methadone maintenance treatment: a receiver operating characteristic analysis. Drug Alcohol Depend. 2006 Feb 1;81(2):129-36. <br /><br />Kornor H, Waal H. From opioid maintenance to abstinence: a literature review. Drug Alcohol Rev. 2005 May;24(3):267-74.<br /><br />Lenné M, Lintzeris N, Breen C, Harris S, Hawken L, Mattick R, Ritter A. Withdrawal from methadone maintenance treatment: prognosis and participant<br />perspectives. Aust N Z J Public Health. 2001 Apr;25(2):121-5.<br /><br />Senay EC, Dorus W, Goldberg F, Thornton W. Withdrawal from methadone maintenance. Rate of withdrawal and expectation. Arch Gen Psychiatry. 1977 Mar;34(3):361-7.<br /><br />Strang J, Gossop M. Comparison of linear versus inverse exponential methadone reduction curves in the detoxification of opiate addicts. Addict Behav. 1990;15(6):541-7.<br /><br />Winstock AR, Lintzeris N, Lea T. "Should I stay or should I go?" Coming off methadone and buprenorphine treatment. Int J Drug Policy. 2010 Oct 16. [Epub ahead of print]<br /> <br />http://dependencyseminars.blogspot.com/2010_10_01_archive.html<br /><br />http://www.redfernclinic.com/c/2005/03/peer-support-for-dependency-problems-12_5218.php4Unknownnoreply@blogger.comtag:blogger.com,1999:blog-2135134153424193830.post-41748246019322421052010-11-17T08:46:00.000+11:002010-11-17T08:50:28.168+11:00Concord Seminar summary on gambling issues. Tuesday 3rd August 2010.The 4th Concord Seminar of 2010, “Is pathological gambling an addiction? You bet it may or may not be!” was presented by Alex Blaszczynski, Professor of Clinical Psychology and Director of the Gambling Treatment Clinic at the School of Psychology, University of Sydney. He has written a self-help manual, "Overcoming Compulsive Gambling". He is editor of International Gambling Studies and Assistant Regional Editor for the journal ‘Addiction’.<br /><br /><br />The presentation covered the definitions and epidemiology of problem and pathological gambling, their impacts on self and others; the multifactorial etiology of gambling problems; cognitive distortions and implications for treatment; and the “pathways” model for understanding etiology and matching treatment interventions. <br /><br />While pathological gambling (PG) (recurrent gambling despite severe negative consequences and/or repeated unsuccessful attempts to cease) remains classified in DSM -IV-TR (A.P.A., 2000) among the impulse control disorders (along with kleptomania and pyromania), its diagnostic criteria since DSM III have come more closely to resemble those substance use disorders. In DS-V, it is proposed to reclassify the condition as a non-substance behavioural addiction. By contrast, ‘problem’ gambling is defined by harms to the individual player, their family and/or the wider community. This resembles the definition of harmful substance use in ICD-10. <br /><br />There has been a worldwide increase of legalized forms of gambling, starting in the USA in 1968 with the New Hampshire lotteries; in Australia with the 1973 West Point Casino; in Britain with the1978 Royal Commission into Gambling and large increases in Europe in the 1990s and in Asia in 2000s. Electronic gaming machines have become increasingly common while the current spectacular growth area is in online gambling.<br /><br />The prevalence of moderate to severe problem gambling is similar in Australia (2.7%) and in the USA (3.0%). Estimates vary widely for prevalence of pathological gambling (Australia 0.6-1.2%; USA 0.1-1.9%), reflecting the assessment tools used (e.g., South Oaks Gambling Screen versus DSM criteria). <br /><br />The DSM diagnosis of pathological gambling (PG) requires five or more of the following:<br />1. Preoccupation (psychological dependence & salience) <br />2. Increased amount gambled (tolerance)<br />3. Irritability/restlessness on cessation (withdrawal)<br />4. Escape from stress (negative reinforcement & motivation)<br />5. Chasing losses (erroneous & distorted cognitions)<br />6. Lying <br />7. Repeated failure to cease (impaired control) <br />8. Illegal acts <br />9. Risked significant relationships <br />10. ‘Bailout’ (relatives or friends paying gambling debts) <br /><br />The criteria of salience, tolerance, withdrawal, impaired control and continuing despite knowledge of harm have obvious parallels with substance dependence, and suggest the likely involvement of meso-limbic/orbito-frontal reward systems in positive and negative reinforcement, underpinning classical and operant conditioning in the development of craving, and impulsive decision-making in pathological gambling.<br /><br />However, certain other features of pathological gambling bear less close comparison with substance dependence. One example is the mediating function of erroneous and distorted cognitions such as the “gambler’s fallacy”, the mistaken belief that the chances of winning over time increase (in fact the chances of winning remain the same at each point in time, and losses are cumulative over time). A recent published paper (Slutske et al 2010), reported that recovery from PG is commonly achieved in the absence of abstinence, ie with a return to “controlled gambling”, a further difference from most instances of substance dependence, where a return to controlled use is exceptional (see Stanton Peele for the contrary view for alcohol and drug use).<br /><br />Indeed the significance of tolerance or withdrawal, two defining elements of “gambling as an addiction”, remains unclear. A recent study (Blaszczynski et al 2008) found that increased bet size was not related to the need to maintain excitement or arousal levels, as in an addictive model, but rather were consistent with a cognitive model in which accumulating debts coupled with erroneous perceptions lead the gambler to increase bet size, with larger bets required to win enough to meet financial obligations. While withdrawal features in gambling are comparable in severity and character (depression, general discomfort, irritability/agitation, restlessness, anxiety and headache) to alcohol withdrawal, it remains unclear whether these symptoms “result from the inability to gamble or from the loss of an avoidant stress coping strategy”.<br /><br />As for substance dependence, gambling has a multifactorial etiology. There is a strong association of PG with parental gambling and genetic transmission is estimated to account for 40-54% of variance of risk for developing PG (Shah et al., 2005). Other factors include environmental factors such as access to venues, ease of accessing money, advertising, community and cultural attitudes, ethnicity and lower socioeconomic status. <br /><br />In terms of comorbidity, 40% of PG have current substance use disorders, 75% suffer major depression, 40% report serious suicidal ideation. It is estimated that approximately 1.7% of Australian suicides are gambling-related. PGs score high for impulsivity, risk-taking, substance use disorders, and borderline, anti-social, narcissistic personalities. Some 60% commit illegal acts to support their habit, usually non-violent property crimes. <br /><br />There are gender differences, in that men are more likely to engage in wagering and online and sports gambling; women have a bimodal distribution of young and 45yo gambling. Early onset (before age 20) is almost universal in PG, fostered by family examples of gambling, and gifts such as scratch lotteries. The average age at treatment seeking is in the mid to late 30s. <br /><br />The problems associated with problem and pathological gambling are wide ranging, as the person slips into borrowing and financial strife, sometimes into theft and lying, with impacts on work, legal problems, family problems including neglect, domestic violence and family breakdown, increasing stress, worry and depression, even personality change (irritability, becoming withdrawn).<br /><br />The impacts on spouses can be enormous, including loss of trust and sense of security, loss of savings, superannuation, even the marital home, or the partner forced to resume or increase work hours. Domestic violence, emotional and physical and verbal abuses are common (often against the gambler). Children of gamblers may suffer confusion, insecurity and poor self esteem, emotional neglect, exposure to domestic arguments/violence, as well as adverse role modeling and vicarious learning.<br /><br />By way of example, Professor Blaszczynski drew our attention to the structural characteristics of electronic gaming machines (EGMs). They operate within a social, alcohol-licensed environment and provide continuous, rapid cycle, multi-line multi-credits, many near wins, requiring minimal skill and fostering erroneous beliefs. The random ratio schedule of reinforcement (wins) is the most resistant to extinction of all reinforcement schedules, perhaps because of the intensity of the mounting excitement and arousal created by the unpredictability of a reward. This forms an interesting contrast to substance use disorders in that the effect of most psychoactive substances is, comparatively, predictable and constant (as long as the drug supply is secure). <br /><br />Professor Blaszczynski pointed to the multiple factors interacting in an etiological model for PG: neurobiological/genetic factors as with substance dependence, interacting with personality and with environmental factors including family and peer group influences, and the wider socio-cultural setting of gambling. <br /><br />This model resembles the bio-psycho-social framework generally used for conceptualising substance use disorders. One distinct difference however is the central role of belief schemas that have a mediating function in the development of problem and pathological gambling. These include the “gambler’s fallacy” mentioned above, but also superstitious beliefs (rituals, talismanic objects, cognitive ‘prayers’, promises, bargaining), biased evaluation, illusions of control and belief in the role of personal skill.<br /><br />Erroneous cognitions are common in pathological gamblers (PG) and non-pathological gamblers alike, although superstitious beliefs are more common in PG, and PG are more likely to show make increasing estimates of the chances of winning during a session of play. Knowledge of the statistical reality of gambling itself does not prevent irrational beliefs during play. <br /><br />The approaches to reducing harms from gambling, like those for substance use disorders, range of from public health measures to psychological and pharmacological therapies. As the risk of PG increases with consumption, measures to reduce overall consumption would be expected to have benefit: as with substance use disorders, consumption is skewed, with mean higher than median, and a small number of people accounting for a large amount of consumption. Taxation revenue incentives severely impede a regulatory public-health approach to gambling problems. <br /><br />Self-help groups such as Gamblers Anonymous are effective for a significant minority of people. However, drop-out rates are very high. <br /><br />Cognitive therapy is beneficial in 75-80% of cases resulting in the reduction of cognitive distortions and levels of gambling behaviour, motivation and urges to gamble. This form of therapy aims to inform gamblers that gaming machines are recreational devices on which you spend money: while it is possible to win in the short-term, in the long term, in all but the most unusual cases and extraordinary circumstances, this outcome is virtually impossible. <br /><br />Behavioural interventions are designed to diminish the arousal associated with gambling, and include aversive therapy, imaginal desensitization, and stimulus control and cue exposure techniques. Positive outcomes are achieved in 20%-70% of PG with reduced arousal associated with gambling stimuli and consequently diminished urges to gamble.<br /><br />The posited underlying neurobiological mechanisms of gambling suggest potential benefit of psychopharmacological interventions, however studies of lithium, SSRIs, naltrexone and olanzepine have given mixed and overall disappointing results. The studies to date have been limited by small size, high drop-out rates, short follow-up and varied outcome measures. <br /><br />A further problem in evaluating treatments is that PGs do not form a homogeneous group. Accordingly, Blaszczynski and Nower (2002) have proposed a “pathways model” which distinguishes among three more or less distinct groups of PG, with implications for treatment matching. <br /><br />A first pathway, encompassing mainly behaviourally conditioned gamblers, is characterized by a social context of gambling, with wins generating excitement, reinforcement and cognitive distortions leading to poor decisions. These people have less dissociation and more absorption in their gambling, briefer histories and either less severe gambling or rapid escalation in response to defined stress. They have a background of childhood and family stability, with less severe psychopathology. Substance abuse onset tends to follow rather than precede gambling problems. Cognitive-behavioural interventions are most likely to be effective with this group.<br /><br />A second pathway is in people with indicators of prior “emotional instability, poor coping, affective dysregulation, impulsivity, oppositional behaviour, suicidality and abusive/discordant family backgrounds”. Impulsivity is a mediating factor in development of gambling, a manifestation of emotional distress, rather than trait impulsivity; these people tend to be more introverted and ‘neurotic’. More intensive cognitive-behavioural therapy is required than for than Pathway 1, with stress-coping and problem-solving strategies to deal with anxiety and depression. Other elements of treatment include financial counseling, management of substance use and mental heath comorbidities, and supportive therapy to address family issues. Suicide risk assessment is especially important. <br /><br />The third pathway encompasses a group with: early onset problem gambling; early history of family instability, abuse and neglect; high levels of impulsivity and anti-social behavior; poor performance at school (inattentive, disruptive); extroverted and dramatizing profile; and involvement in video games, sports, and other activities with a high degree of stimulation. They gamble for stimulation, excitement and arousal. Substance use problems and a broad spectrum of criminal behaviours are common, and often precede PG. While cognitive-behavioural therapy is important for these people too, there is a greater focus on limit setting, dealing with substance use and mental heath comorbidities, addressing narcissism and ego needs, and teaching adaptive stress-coping styles and problem-solving strategies, within the context of their larger scale psychosocial dislocation/dysfunction. This is the hardest group to treat. <br /><br />In the second half of the seminar, Professor Blaszczynski pointed to some of the ways people can be trapped by erroneous beliefs encouraged by the gambling industry. A common belief, for example, is that certain poker machines may be lucky, or their time has come for a jackpot: although the “take” of these machines is regulated by statute and strictly policed, each machine has a factory setting which cannot be altered for the life of the machine, which determines the proportions of payouts: some machines are thus incapable of producing a large jackpot BUT ARE NOT LABELLED AS SUCH. Texas Hold’em Poker on-line is a common trap, as the participant can be easily persuaded that it is primarily a game of skill, and seduced by early wins (deliberately arranged by the provider) to be believe in their own superior skill. Free-to-play sites are designed to provide a much higher probability of winning giving the player the impression that they are skillful and can win. However, the probability is adjusted such that the risk of losing increases when they enter the play-for-money site.<br /><br />Finally we were shown a poker machine simulation software program that is useful in treatment. In this program a person can choose the size and frequency of their bets and “fast forward” the play over a long time frame, reading their winnings off as rising and falling numbers on the screen, simultaneously shown as a graph. A person can repeat this as many times as they like, and so simulate the experience of as many games as they like: despite occasional blips representing wins, the outcome is always inexorably to lose money. <br /><br />The longer you play the more you will lose. <br /><br />The attendees at this Concord seminar evaluated it as one of the best ever. The small attendance was curious: could it be that health professionals don’t “see” gambling problems very often, or might gambling be in the “too hard basket”? Routinely asking about gambling in a substance use history might give some surprises!<br /><br />Summary by Richard Hallinan based on Alex Blaszczynski’s presentation and power point.<br /><br />References:<br /><br />Blaszczynski A, Walker M, Sharpe L and Nower L. 'Withdrawal and Tolerance Phenomenon in Problem Gambling', International Gambling Studies, 2008. 8 (2), 179-192<br /><br />Slutske WS, Piasecki TM, Blaszczynski A, Martin NG. Pathological gambling recovery in the absence of abstinence. Addiction. 2010 Dec;105(12):2169-75<br /><br />Blaszczynski A, Nower L. A pathways model of problem and pathological gambling. Addiction. 2002 May;97(5):487-99<br /><br />Shah KR, Eisen SA, Xian H, Potenza MN. Genetic studies of pathological gambling: a review of methodology and analyses of data from the Vietnam Era Twin Registry. Gambl Stud. 2005 Summer;21(2):179-203Unknownnoreply@blogger.comtag:blogger.com,1999:blog-2135134153424193830.post-61977937051205945092010-10-10T17:56:00.002+11:002010-11-28T18:15:39.051+11:00The use of naltrexone implants as an 'exit strategy' from OMT.This is a summary of Ross Colquhoun’s presentation, and the case studies, from our Concord Seminar February 2010, “The Exit Strategy Part 1”. Summary and comments from Richard Hallinan, and responses kindly provided by Ross Colquhoun (in capitals). <br /><br /><br />Ross Colquhoun described his own extensive experiences with ROD and naltrexone implants. <br /><br />He reiterated that the implants can provide 6-12 months protection against heroin overdose. He explained that swellings at the site of naltrexone implants are usually due to an allergic reaction which can be treated with prednisone, and do not require antibiotics or removal of the implant as sometimes is done by medical doctors <br /><br />RC mentioned the correspondence in MJA in 2009 (Degenhardt et al) reporting 12 cases of presentations to hospital emergency departments in Sydney following on naltrexone implant (it is not clear how many of these implants were performed at RC’s facility). RC argued, as did a number of correspondents to the journal, that the original report had failed to distinguish between ROD and implant-related symptoms. <br /><br />COMMENT RC: ONLY ONE OF THE ADVERSE EVENTS RELATED TO AN IMPLANT (AN EXCLUSION) AND ALL THE OTHERS RELATED TO WITHDRAWAL FROM A DETOX OF ONE SORT OR ANOTHER AND WOULD HAVER HAPPENDED IRRESPECTIVE OF WHETHER THE PERSON HAD AN IMPLANT OR NOT<br /><br />Comment RH: as the two procedures are performed together in these instances, it is indeed problematic attempting to distinguish the cause of severe symptoms when they occur. There is no research to indicate whether the implant itself might intensify the opioid withdrawal symptoms. <br /><br />COMMENT RC: THERE IS A LOT KNOWN ABOUT NALTREXONE AND THE IMPLANT IS NALTREXONE DELIVERED OTHER THAN ORALLY. ON THE OTHER HAND ANYONE AT ALL FAMILIAR WITH WITHDRAWAL WOULD HAVE SEEN THE SAME SYMPTOMS PRE-IMPLANT ERA AND NOTHING HAS CHANGED. I HAVE DATA ON ALL THIS, WHICH I CAN MAKE AVAILABLE<br />IF WANTED<br /><br />RC showed data from his published paper (Journal of Opioid Management 2005). He stated that he had followed a total of 43 patients who had received naltrexone implants compared with 41 who received oral naltrexone, with telephone self-reported (or reported by a contact person) heroin use clearly lower in the implant group than the oral naltrexone group. Asked whether this was therefore a prospective study with 100% follow up at 6 months, RC explained that the follow up was indeed very good and approaching 100%, though it fell off at 12 months (data unpublished as yet). <br /><br />COMMENT RC: THIS DATA WAS INCLUDED IN THE PUBLISHED PAPER AND SOME 20% WERE NOT CONTACTABLE AT 12 MONTHS AND WERE NOT INCLUDED IN THE ABSTINENCE GROUP <br /><br />Comment RH: my original reading of this paper was that it was retrospective, with the numbers in each group reflecting those who had been successfully contacted. Further data such as the denominator of all patients treated at the study centre in the time period would be needed clarify this important methodological question. <br /><br />COMMENT RC: IT WAS NOT RESTROSPECTIVE, ALTHOUGH SUBJECTS WERE NOT RANDOMLY ALLOCATED TO EITHER GROUP BUT CHOSE TO HAVE AN IMPLANT OR TO TAKE ORAL NTX AT A TIME WHEN THERE WAS A MUCH SMALLER PROPORTION OF PEOPLE WHO CHOSE AN IMPANT. NOW IT IS WELL OVER 90%.<br /><br />The protocol for managing ROD has evolved since Ross Colquhoun’s unit started doing it. Sedation with benzodiazepines (midazolam and flunitrazepam) is the mainstay, such that the person experiences but does not remember withdrawal symptoms. Naltrexone is given orally while the patient is sedated but not unconscious. This appears to precipitate opioid withdrawal much more profoundly than the obligatory naloxone challenge, which is however still given at some point during the procedure. Dexamethasone is now routinely given to prevent pulmonary edema, which previously occasionally happened during or after ROD. Octreotide has dramatically reduced gastrointestinal symptoms especially vomiting. Most patients are observed overnight by an experienced nurse.<br /><br />Asked about accreditation, RC stated that the facility was not accredited by ACHS. However the doctors working there carried indemnity insurance, usually General Practice Level 1, which covers minor surgical procedures under sedation. <br /><br />Dr Alex Wodak pointed to RC’s slide listing people he considered suitable for naltrexone implant. These included persons stable on MMT. Dr Wodak asked how this could be reconciled with the wording of the TGA Special Access Scheme A, under which Category A patients are defined as "persons who are seriously ill with a condition from which death is reasonably likely to occur within a matter of months, or from which premature death is reasonably likely to occur in the absence of early treatment". Specifically he asked how stable MMT patients could be considered reasonably likely to die within months. RC responded by pointing to the second clause, that heroin addiction is reasonably likely to cause death in the absence of early treatment, and rejected the claim that this was somehow using a “loophole” in the regulation. <br /><br />Comment RH: one would have to ask whether stable MMT patients are seriously ill.<br /><br />COMMENT RC: STUDIES FROM ENGLAND AND SCOTLAND INDICATE THAT DEATHS ASSOCIATED WITH METHADONE APPROACH 60-70%. FIGURES ARE NOT AVAIALBLE HERE, HOWEVER WE EXPECT THAT RATE TO BE COMPARABLE. METHADONE IS A HIGHLY ADDICTIVE AND DANGEROUS DRUG THAT CAN RESULT IN OVERDOSE AND DEATH ESPECIALLY WHEN USED WTH OTHER CNS DEPRESSANTS<br /><br />In response to the query about the role of the TGA, Ross Colquhoun told the audience that the TGA approved of his use of category A for provision of naltrexone implant treatment, and that he had documentary evidence of this. He further stated that while he had had doubts about using Category A notification for naltrexone implants for alcohol dependence, the TGA had actually encouraged him to do so. <br /><br />COMMENT RC: IN 10 YEARS THE TGA HAD NEVER QUERIED THE USE OF SAS PROVISIONS TO ENABLE US TO USE NTX IMLPANTS<br /><br /><br />In the second half of the seminar, two case studies were presented. <br /><br />Acknowledging that Ross Colquhoun could provide many examples of people who had simply done very well with naltrexone implant, the cases presented were more complex.<br /><br />The first was of a 26yo man (at the time of a naltrexone implant in mid 2009) who had first used heroin age 20, snorting then quickly IDU. He kept down responsible and highly paid work. His first MMT was 2005, and there was an unsuccessful transition to BMT from higher dose MMT in 2006, then MMT again till 2009. There was a strong family history of addiction, and the patient had previous problematic benzodiazepine use, with “panic disorder” treated by several GPs with benzodiazepines including oxazepam and alprazolam. During 2008 he had several driving offenses, including unlicensed driving x 3; and intoxicated driving causing an accident. His apparent inability to conceive a child led to stress with his partner, who was keen to have baby. He had hypogonadotrophic hypogonadism (very low testosterone 2-4 nmol/L), obesity, steatohepatitis and gynaecomastia while on MMT. During opioid treatment there was ongoing use of benzodiazepines, alcohol, stimulants (cocaine and amphetamines). He showed great impulsivity and enthusiastic suggestibility with marked inability to follow through on his resolutions, including investigation and treatment of his liver problems, infertility and hypogonadism, relapse prevention counseling, and psychologist counseling. <br /><br />Discontent, and under duress from his wife (threatening divorce) and her parents (who offered to pay), he signed up for ROD and naltrexone implant, against advice from the treating addiction physicians. 10 days post implant insertion, he had the implant removed by a GP, owing to allegedly unbearable symptoms, despite being advised against removal by his addiction specialist and a public hospital. He relapsed into heroin use, spent a large settlement from his divorce on heroin, eventually returned to MMT. After another brief transfer to BMT he expressed discontent at not able to enjoy heroin, and sought MMT again.<br /><br />This man died of a heroin overdose on 3rd day of MMT induction, having missed 2 days’ dosing. <br /><br />The discussion started with the observation that this counts in the statistics as a death during methadone induction, but under the current reporting mechanisms in NSW, will not be connecting with ROD or naltrexone implant in any way. The question was posed whether naltrexone implant treatment had in fact destabilized this patient. From the floor came the comment that this patient could not have been called stable at any time. On the other hand, during previous MMT he was at least alive and working. <br /><br />It was evident that the implant provider had not been made aware of the true extent of this man’s instability. The addiction specialists considered him unfit for implant on grounds of: <br />1. previous failure to achieve abstinence on MMT or BMT and his lack of commitment to opioid abstinence<br />2. ongoing other drug use<br />3. impulsivity<br />4. his being under duress to have the treatment<br />5. his underlying anxiety disorder.<br />6. his constant seeking for a quick, preferably chemical, fix to his problems.<br />7. his previous failure to engage in counseling<br /><br />This case highlights the need for better lines of communication between providers of opioid pharmacotherapies and the providers of ROD and naltrexone implants.<br /><br />COMMENT RC: IN THIS CASE HE GAVE FULL AND FREE CONSENT TO UNDERGO NTX TREATMENT AND WAS ABLE TO SUSTAIN A PERIOD OF ABSTINANCE FROM OPIATES. BEING PROFOUNDLY UNHAPPY WITH HIS LIFE AND HAVING TO RESUME MMT SUICIDE COULD NOT BE RULED OUT. IT IS EVIDENT THAT THE PERIOD ON NTX DID NOT RESULT IN HIS DEATH, ALTHOUGH PERHAPS INDIRECTLY AS HE REALISED HE WAS NOT ABLE TO SUSTAIN HIMSELF WITHOUT OPIATES AND THAT HE DETESTED THE NOTION OF HAVING TO REMAIN ON MMT FOR THE FORESEEABLE FUTURE. IN MANY WAYS HE WOULD BE NOT DISSIMILAR TO MANY WHO PRESENT FOR TREATMENT, BUT WHO THEN DO VERY WELL.<br />HIS OUTCOME WAS VERY UNUSUAL IN OUR EXPERIENCE.<br /><br />The second case was of a 48yo professional dancer “Nelly M’Elba” who started her current episode BMT in 2002 after a prior 28 years heroin IDU, including several episodes of MMT. There were extended periods without heroin between periods of opioid treatment. There was regular THC use but little alcohol, and occasional use of stimulants especially cocaine. In 2004 Nelly did rapid detox with naltrexone implant and at last report still states “it was successful”. Although they were told that naltrexone was mainly good for alcoholism, but actually Nelly increased her alcohol to 60-75 g/day in the months after the implant. Nelly also got diazepam from the implanting doctor about 5/12 after the implant, and continued this until taking up heroin again after 10 months. 15-18 months after implant Nelly was worried about an unsightly lump interfering with her with dancing work. The implanting Dr was reported to be uncontactable, overseas. The addiction specialist discussed the case with the manufacturer, who stated such lumps are unusual, almost always disappear by 24 months post implant, and continue to release naltrexone while they are still not dissolved. If not dissolved by 24 months, the manufacturer suggested referral to surgical clinic for advice. <br /><br />Three happy endings: <br />1. Nelly’s lump went way by 26 months. <br />2. Nelly’s best friend (and colleague) who had ROD and naltrexone implant at the same time, had a second implant and at last report was also back on buprenorphine treatment. <br />3. “Perry”, a naltrexone implant success story had had no heroin or benzodiazepines in 2 years. Perry showed Nelly his two 'expired' implants, 12 and 18 months old respectively, still prominent and unsightly, but he had been told they may take up to two years to dissolve. He was not worried in the slightest about the lumps, just happy to be free of drugs. <br /><br />A less happy ending:<br />The implanting doctor in Nelly’s case is apparently still overseas. It was reported in the press that he had no legal representation throughout a court case in the NSW Supreme Court in which $6 million was awarded against him (in May 2009), in relation to brain damage sustained by a patient prescribed certain medications to withdraw from drugs. It was reported that he had no medical indemnity insurance at the time.<br />http://www.dailytelegraph.com.au/news/ex-junkie-wins-6m-but-wont-get-a-cent/story-e6freuy9-1225707964425<br /><br />Comment RH: although the newspaper report is on public record, the precise circumstances regarding indemnity insurance are not. Nonetheless this case raises important questions about the need to ensure that people providing addiction treatment have an appropriate level of indemnity insurance; this is particularly important for treatment which are unapproved or lack published evidence, and for the use of TGA-unregistered treatments. <br /><br />As to cost, ROD procedure is $7800, with implant $5600. A subsequent implant requiring no ROD costs $1400. Ross Colquhoun made the point that this is a low cost, compared with the alternative possibility of many years of opioid agonist treatment with no “Exit Strategy”.<br /><br />The subject of the “Exit Strategy” for methadone and buprenorphine maintenance treatments will be taken up in the second seminar on this subject, in December 2010. <br /><br />References<br /><br />Colquhoun R, Tan D, Hull S. A comparison of oral and implant naltrexone outcomes at 12 months. J Opioid Manag. 2005 Nov-Dec;1(5):249-56.Unknownnoreply@blogger.comtag:blogger.com,1999:blog-2135134153424193830.post-86614259944782846292010-06-26T03:54:00.000+10:002010-06-27T13:40:42.238+10:00NEW PROGRAM FOR 2010.Concord Seminar sessions for 2010.<br /><br />2/02/2010 The Exit Strategy Part 1: Naltrexone Implants: What does the evidence tell us? Ross Colquhoun<br /><br />20/04/2010 Wet Brain: Alcohol and the Brain - delerium, confabulation, amnesia, and collapse. Prof Paul Haber<br /><br />8/06/2010 The Other Hepatitis"- An Update on Hepatitis B Part 2 Dr Gail Matthews<br /><br />Tues 3/08/2010 - Is pathological gambling an addiction? You bet it may or may not be! Prof Alex Blaszczynski<br /> <br />Tues 21/09/2010 - Mentally Disordered or Mentally Ill? The NSW Mental Health Act, and how to use it in drug and alcohol settings and in community practice. <br />Dr Glenys Dore & Dr Lisa Juckes <br /> <br />30/11/2010 The Exit Strategy Part 2: Is there life after methadone? Prof Nicholas Lintzeris<br /><br /><br />Organisation:<br /><br />No booking necessary. 6.30pm for introductions and refreshments, session starts 7pm. Parking available at front of Concord Hospital. Conference Room 1, opposite hospital cafeteria. For information call Dr Richard Hallinan or Dr Andrew Byrne (02) 9319 5524. GP CPD credits available.<br /><br />This seminar series has been set up as a regular activity attracting 2 points/hours for RACGP QA&CPD (activity number 745701)<br /><br />Objectives and prereading will be circulated prior to each seminar (some details below).<br /><br />Sponsored by Reckitt Benckiser, manufacturers of buprenorphine products.<br /><br /><br />THE CONCORD DEPENDENCY SEMINARS 2010 CALENDAR AND PRE-READING:<br /><br />2/02/2010 - The Exit Strategy Part 1: Naltrexone Implants: What does the evidence tell us?Ross Colquhoun & Richard Hallinan<br /><br />Naltrexone implants have been used for opioid dependence in Australia since about 2001, usually following "rapid opioid detox" procedures. So far they are only used in a small number of centres. Since 2001 published literature has built up, much of it post hoc and naturalistic, but recently some prospective studies, including 2 randomised controlled trials have been published. What does the evidence tell us about these devices? Are they ready to enter the mainstream of addiction treatment? In this seminar Richard Hallinan will present a brief overview of the published literature, and Ross Colquhoun will describe and present data on his experiences using naltrexone implants in Sydney over a number of years. In the second half several case studies will be presented, with discussion.<br /><br />Pre-reading: <a href="http://www.redfernclinic.com/concord/2009/12/concord-seminar-series-tues-1st.php4">http://www.redfernclinic.com/concord/2009/12/concord-seminar-series-tues-1st.php4</a><br /><br />20/04/2010 - Wet Brain: Alcohol and the Brain - delirium, confabulation, amnesia, and collapse. Professor Paul Haber.<br /><br />In this seminar Dr Paul Haber will take us through alcohol's wide range of acute and chronic neurological neuropsychological harms, with an emphasis on diagnostic dilemmas, problems not to be missed, harm reduction measures, safety issues and other pitfalls in community practice. Case studies of collapse, confusion, memory loss, and gait impairment will illustrate the importance of alcohol as one of the "great mimics" of modern medicine.<br /><br /><br />8/06/2010 - The Other Hepatitis - An Update on Hepatitis B Part 2. Dr Gail Matthews, Infectious Diseases Physician, St Vincent’s Hospital, Darlinghurst<br /><br /><br />Although less common in injecting drug users than Hepatitis C (HCV), Hepatitis B (HBV) is common in Australia, and co-infection with Hepatitis C poses particular problems. Part 1 of this seminar pair looked at trends in the epidemiology of Hepatitis B in Australia, how to assess and manage Hepatitis B and to prioritise for treatment, as well as about new directions in pharmacotherapies. By popular demand from participants in the first seminar, we will revisit these themes with more case studies covering diagnosis and assessment, indications for treatment, coinfection with HCV or HIV, and special issues for substance using populations.<br /><br />For pre-reading: <br /><a href="http://www.redfernclinic.com/concord/2008/07/other-hepatitis-update-on-hepatitis-b.php4">http://www.redfernclinic.com/concord/2008/07/other-hepatitis-update-on-hepatitis-b.php4</a><br /><br /><br />3/08/2010 - Is pathological gambling an addiction? You bet it may or may not be! Prof Alex Blaszczynski<br /><br />Pathological Gambling is classified in DSM IV among the impulse control disorders, yet it appears to share many features with, and its diagnostic criteria modelled after, substance use disorders. What do they have in common, and can drug and alcohol services have a role in dealing with the problem? Do medications help? How should drug and alcohol specialists handle people with concurrent substance use and gambling problems? Can Protective Estates Orders be invoked? Cases studies will present gambling problems in isolation and in combination with substance use problems. Alex Blaszczynski is a Professor of Clinical Psychology and the Director of the Gambling Treatment Centre in the School of Psychology, University of Sydney and was Head of the Department of Medical Psychology at Westmead Hospital. He has conducted randomized controlled outcome cognitive and behavioural treatment studies, and investigated the prevalence of co-morbid substance abuse, withdrawal and tolerance phenomenon, and suicidality in pathological gamblers seeking treatment. He has written a self-help manual, "Overcoming Compulsive Gambling". He is editor of International Gambling Studies and Assistant Regional Editor for Addiction. <a href="http://www.psych.usyd.edu.au/staff/alexb/">http://www.psych.usyd.edu.au/staff/alexb/</a><br /><br />21/09/2010 Mentally Disordered or Mentally Ill? The NSW Mental Health Act, and how to use it in drug and alcohol settings and in community practice. Dr Glenys Dore and Dr Lisa Juckes.<br /><br />In this seminar Dr Glenys Dore and Dr Lisa Juckes will take us through the maze of the NSW Mental Health Act, including the Temporary Protection Order, Continuing Treatment Order, the role of the Crisis Team of the local Mental Health Unit, the Mental Health Review Tribunal, and Community Treatment Orders, with a special emphasis on their use in people affected by alcohol and other drugs. There will also be a brief introduction to Protective Estates Orders and the workings of the Protected Estates Act 1983. Case studies will illustrate how these laws and regulations are best used in community practice and drug and alcohol settings.<br /><br /><br />30/11/2010 - The Exit Strategy Part 2: Is there life after methadone? Dr Nick Lintzeris & Richard Hallinan<br /><br />A common complaint about opioid substitution treatment is that there is "no exit strategy". People talk of liquid handcuffs, and critics claim OST just keeps the people addicted forever. How should the health professionals respond to a request for reductions toward abstinence? Is there any evidence to guide professional practice? Dr Nick Lintzeris (and Richard Hallinan) will present an overview of published evidence about duration of OST treatment, withdrawal and reduction regimens, "cycling in and out of treatment", the relative ease of reductions for methadone and buprenorphine and other matters. Case studies and discussion in the second half.Unknownnoreply@blogger.comtag:blogger.com,1999:blog-2135134153424193830.post-72536678486533207492010-06-20T21:41:00.000+10:002010-07-28T21:43:16.658+10:00Concord Seminar on gambling problems vs. chemical addiction. Tuesday 3rd August.3/8/2010 - Is pathological gambling an addiction? You bet it may or may not be! Speaker: Prof Alex Blaszczynski. <br /><br />Pathological Gambling is classified in DSM IV among the impulse control disorders, yet it appears to share many features with, and its diagnostic criteria modelled after, substance use disorders. What do they have in common, and can drug and alcohol services have a role in dealing with the problem? Do medications help? How should doctors, including drug and alcohol specialists, handle people with concurrent substance use and gambling problems? Can Protective Estates Orders be invoked? <br /><br /><br />Cases studies will present gambling problems in isolation and in combination with substance use problems. <br /><br /> <br />Alex Blaszczynski is a Professor of Clinical Psychology and the Director of the Gambling Treatment Centre in the School of Psychology, University of Sydney and was Head of the Department of Medical Psychology at Westmead Hospital. He has conducted randomized controlled outcome cognitive and behavioural treatment studies, and investigated the prevalence of co-morbid substance abuse, withdrawal and tolerance phenomenon, and suicidality in pathological gamblers seeking treatment. He has written a self-help manual, "Overcoming Compulsive Gambling". He is editor of International Gambling Studies and Assistant Regional Editor for Addiction.<br /><br /> <br /><br />Learning objectives: at the end of this seminar the participant will be able to: <br /><br /> <br />1. show knowledge of the epidemiology of problem gambling and gambling related harms in Australia, including gender, age, socioeconomic and ethnic factors and comorbid substance use.<br /><br /> <br />2. demonstrate understanding of the multifactorial etiology of gambling pathology, including availability and modes of gambling, genetic predispositon, personality traits and disorders (extraversion, impulsivity), and environmental factors. <br /><br /> <br />3. show awareness of the role of irrational beliefs and erroneous perceptions (superstition, illusions of control, expectancies of winning, attibutional bias, selective memory) in problem gambling and the implications for treatment<br /><br /> <br />4. show understanding of the association of gambling with financial and interpersonal problems, with crime and depression, and of risk factors for suicide.<br /><br /> <br />5. show understanding of the roles of psychotherapies, pharmacotherapies and harm reduction initiatives in promoting controlled gambling and gambling abstinence. <br /><br /> <br />Pre-reading<br /><br />International Gambling Studies, Vol. 8, No. 2, 179–192, August 2008<br />Withdrawal and Tolerance Phenomenon in Problem Gambling<br />ALEX BLASZCZYNSKI, MICHAEL WALKER, LOUISE SHARPE & LIA NOWER<br /> <br />The phenomenological similarities between gambling and substance dependence have led to the conceptualization of pathological gambling as an addictive disorder. Tolerance and withdrawal are important features of both disorders, suggesting commonalities in the neurobiological processes associated with neuroadaptational underpinnings. However, there are few empirical studies supporting the presence of tolerance and withdrawal reported in the gambling literature. Moreover, there are no studies comparing the equivalence of tolerance and withdrawal between gambling and alcohol dependence. This study compared tolerance and withdrawal features in samples of gamblers, alcoholics and gamblers who also met criteria for alcohol dependence. In contrast to the addiction model, findings indicate that, while a majority of participants increased bet size, the motivation to do so was not for excitement or to maintain arousal levels as indicated by the DSM-IV-TR but because of cognitive factors related to winning. Results supported the notion that pathological gamblers experienced similar levels of withdrawal symptom severity as alcohol-dependent participants. Further research is needed to evaluate whether those symptoms result from the inability to gamble or from the loss of an avoidant stress coping strategy.<br /> <br /> <br />Addiction. 2002 May;97(5):487-99.<br />A pathways model of problem and pathological gambling.<br />Blaszczynski A, Nower L.<br /> <br />At the moment, there is no single conceptual theoretical model of gambling that<br />adequately accounts for the multiple biological, psychological and ecological<br />variables contributing to the development of pathological gambling. Advances in<br />this area are hampered by imprecise definitions of pathological gambling, failure<br />to distinguish between gambling problems and problem gamblers and a tendency to<br />assume that pathological gamblers form one, homogeneous population with similar<br />psychological principles applying equally to all members of the class. The<br />purpose of this paper is to advance a pathways model that integrates the complex <br />array of biological, personality, developmental, cognitive, learning theory and<br />ecological determinants of problem and pathological gambling. It is proposed that<br />three distinct subgroups of gamblers manifesting impaired control over their<br />behaviour can be identified. These groups include (a) behaviourally conditioned<br />problem gamblers, (b) emotionally vulnerable problem gamblers and (c) antisocial,<br />impulsivist problem gamblers. The implications for clinical management are<br />discussed.<br /> <br /> <br />Suicide Life Threat Behav. 2003 Spring;33(1):88-98.<br />Pathological gambling and suicidality: an analysis of severity and lethality.<br />Maccallum F, Blaszczynski A.<br /> <br />Pathological gambling represents a major public health issue. Risk factors for<br />suicide such as major depression, substance abuse, marital breakdown,<br />unemployment, financial crises, and legal difficulties are commonly found in<br />populations of pathological gamblers. The objective of this study was to<br />systematically investigate the nature of suicidal behavior among<br />treatment-seeking pathological gamblers and its relationship to gambling<br />characteristics and depression. Indices of suicidality were assessed in a sample <br />of 85 treatment-seeking diagnosed pathological gamblers. High rates of suicidal<br />ideation, suicidal plans, and attempts were found; however, no clear relationship<br />was observed between suicidality and indices of gambling behavior. Depression<br />rather than gambling specific characteristics, marital difficulties, or the<br />presence of illegal behaviors appear to be related to the risk of suicidality.<br /> <br />Aust N Z J Psychiatry. 2002 Jun;36(3):411-5.<br />Pathological gambling and comorbid substance use.<br />Maccallum F, Blaszczynski A.<br /> <br />OBJECTIVE: The objective of this study was to determine the rates of substance<br />use problems in a sample of diagnosed pathological gamblers seeking treatment in <br />a university teaching hospital cognitive behavioural outpatient clinic. METHODS: <br />A semistructured interview schedule and the composite international diagnostic<br />interview (CIDI-auto) were administered to assess substance dependence in a<br />sample of 75 poker-machine gamblers meeting DSM-IV and South Oaks gambling screen <br />(SOGS) criteria for pathological gambling. Both the self-reported rates and the<br />proportion meeting criteria for a psychiatric disorder were determined. RESULTS: <br />The rates for substance use disorder within a sample of treatment-seeking<br />pathological gamblers is higher as compared to general population figures. Gender<br />differences were found with more current alcohol-abuse problems reported among<br />male than female participants. Non-alcohol-related substance abuse was relatively<br />lower than rates reported by other studies in the literature. CONCLUSIONS:<br />Substance abuse is a common comorbid condition of pathological gambling and<br />therefore should be screened for in routine clinical assessments. Failure to<br />identify and treat comorbid substance-use disorders in gamblers may lead to<br />higher relapse rates.<br /> <br />Behav Cogn Psychother. 2009 Jan;37(1):49-59.<br />Consequences of winning: the role of gambling outcomes in the development of<br />irrational beliefs.<br />Monaghan S, Blaszczynski A, Nower L.<br /> <br />BACKGROUND: The development and maintenance of gambling and problem gambling <br />with its corresponding irrational beliefs may be fundamentally linked to patterns of<br />wins and losses during electronic gaming machine (EGM) play. METHOD: The current <br />study investigated the extent to which irrational thoughts and erroneous<br />perceptions of chance differed based on individual wins or losses. Undergraduate <br />students (n = 45) completed questionnaires assessing irrational beliefs and<br />perceptions of chance prior to and following EGM play with credits rather than<br />money. RESULTS: It was found that players who lost reported a significantly<br />greater decrease in irrational thoughts and erroneous perceptions of chance and<br />significantly fewer superstitious beliefs than winning players following play.<br />CONCLUSIONS: Future studies are needed to further investigate the relationship of<br />winning to cognitive distortions to guide education and interventions.Unknownnoreply@blogger.comtag:blogger.com,1999:blog-2135134153424193830.post-25713177083488814632010-05-11T21:00:00.002+10:002010-05-11T21:04:25.765+10:00Prof Paul Haber of alcoholic brain damage. Concord Seminar summary.Wet Brain: Alcohol and the Brain - delirium, confabulation, amnesia, and collapse. <br /><br />In this seminar, Dr Paul Haber looked at the ways alcohol affects the brain, both “direct” effects (intoxication, dependence, withdrawal, hallucinosis and sleep disturbance) and “indirect” effects, ranging from Wernicke-Korsakoff Syndrome to head injury, stroke, intracranial haemorrhage and epilepsy.<br /><br />The corpus callosum, cerebellum and mamillary bodies are areas of the brain most prone to the effects of alcohol, but indeed the whole brain is sensitive to the effects of alcohol. The extent of this susceptibility is perhaps best seen in the globally impaired brain development of the foetal alcohol syndrome.<br /><br />(Dr Haber reminded us to be vigilant: FAS is often first diagnosed in adulthood, and that even late identification and management may improve people’s functioning in life.)<br /><br />Multiple pathology is the rule rather than the exception, even when only alcohol is the injurious agent (as opposed to injury, cerebrovascular disease, hypertension, thiamine deficiency etc).<br /><br />While dopaminergic and opioid neurochemical in the “brain reward pathways” underlie the phenomena of dependence and craving, the syndrome of alcohol withdrawal results from alcohol’s effects at ligand-gated ion channels, especially GABA-A & NMDA receptors. Adaptive changes in response to chronic alcohol consumption, including desensitization of GABA-A and up-regulation of NMDA receptors, lead to the hyperexcitable state of the CNS in alcohol withdrawal.<br /><br />Alcohol withdrawal seizures are an important example of this CNS hyperexcitability. They tend to occur in the first 24 hours of alcohol withdrawal and 90% occur within 48 hours. They occur in 10% of hospital series of alcohol withdrawal (they may be less common in community practice). Risk is proportional to the prior level of alcohol consumption. They are generalised tonic-clonic in 95%, and most are uncomplicated and self limiting, however they are multiple in 25%. The EEG is normal in 90% of cases. Seizures are more likely to happen in people who are metabolically unwell. Alcohol also predisposes to seizures in epilepsy and to brain injury which can be a cause of seizures. <br /><br />Benzodiazepines are effective treatment for alcohol withdrawal (see Cochrane review, Amato et al 2010). Further, in a study of chronic alcohol users who presented to Boston emergency departments after a witnessed, generalized seizure, treatment with intravenous lorazepam was associated with a significant reduction in the risk of recurrent seizures (D’Onofrio et al, N Engl J Med 1999 340:915-9.)<br /><br />We were reminded that in ambulatory settings, claims to have had alcohol-related seizures may more commonly come from people trying to get benzodiazepines, than from true cases.<br /><br />Dr Haber mentioned alcoholic hallucinosis, a rare syndrome (0.6% hospitalised alcoholics; Soyka 2008) which needs to be distinguished from the hallucinations of delerium tremens (DTs) and also from alcohol-related psychotic disorder. They are typically auditory hallucinations, and may be accompanied by paranoia, but with preserved insight. The key to diagnosis is that they occur with a clear sensorium. They may occur while drinking and persist during withdrawal, but the majority settle with abstinence. (Dr Peter Tucker however reminded us that most cases of people hearing voices while drinking alcohol will be chronic schizophrenics, as this condition is relatively common and many schizophrenics “self-medicate” with alcohol and other drugs).<br /><br />Another organic brain syndrome related to alcohol is hepatic encephalopathy. There may be impaired cognitive function, but importantly, this is reversible in early stages, and treatment with lactulose is effective. Most people with hepatic encephalopathy are jaundiced, but bilirubin excretion may be preserved: the mechanism of encephalopathy involves porto-systemic shunting. <br /><br />The essential neuropathology of direct alcohol-related brain damage is white matter atrophy with reduced brain weight. Myelination and axonal integrity are involved. There can also be grey matter neuronal loss, and large neurons are most susceptible, the same neurons affected by Alzheimer’s disease and ageing. These changes are reversible in experimental animals with alcohol abstinence.<br /><br />Alcohol is toxic to the brain independent of thiamine deficiency, but the latter probably causes most of the problem we see in clinical practice, including the Wernicke-Korsakoff syndrome (WKS).<br /><br />Thiamine pyrophosphate is a co-factor in oxidative decarboxylation of α-keto acids. Plant seeds are the major dietary source, but thiamine is removed in processing of white flour and rice. Dr Haber mentioned Dr Clive Harper, of Sydney University, who lead the battle to supplement Australian flour with thiamine, leading to a reduced incidence of<br />deficiency states. <br /><br />Dr Harper’s recent review of “The neuropathology of alcohol-related brain damage” (Alcohol. 2009 Mar-Apr 44(2):136-40.) is available free on Pubmed at <a href="http://www.ncbi.nlm.nih.gov/pubmed/19147798">http://www.ncbi.nlm.nih.gov/pubmed/19147798</a><br /><br />Thiamine is highly water soluble, and is lost in cooking. Average requirements are 1 mg/day. Heavy users of alcohol have reduced dietary intake, reduced absorption and increased requirements, partly owing their unbalanced, carbohydrate heavy diets. <br /><br />The classic triad of Wernicke’s enecephalopathy is present in only 10% of cases, so many cases probably go undiagnosed, or are first diagnosed at autopsy. Confusion is the most common manifestation, with ataxia present in 23% and nystagmus in 29% (with or without horizontal gaze or other palsy)<br /><br />Wernicke’s is a medical emergency: rapid treatment with parenteral thiamine is highly successful, as the changes are largely reversible, while delayed treatment may result in permanent severe disability. <br /><br />A Cochrane review concluded there is insufficient evidence to guide treatment with thiamine (other than to say 200mg better than 5mg!). However, the usual practice is to give it prophylactically in all alcohol users admitted to hospital, as 100mg tds 3-5 days, then 100mg daily until abstinent >3 months (which may mean indefinitely). Thiamine is given parenterally if the patient is unwell or receiving IV fluids, and parenteral treatment should always commence prior to IV glucose, as a carbohydrate load may precipitate Wernicke’s enecephalopathy. If there is any suggestion of confusion or WKS, thiamine should be given 100mg tds by IVI or IMI.<br /><br />The chronic phase of the Wernicke-Korsakoff syndrome, Korsakoff’s psychosis, is dense anterograde amnesia with confabulation, apathy and gross functional impairment, reflecting damage to the anterior nucleus of thalamus. Estimated prevalence is 12% in alcoholics, so it is still common. It may overlap with features of alcohol-related cerebrocortical degeneration, including frontal lobe syndrome (with impaired abstract thinking and executive function, disinhibition and personality change) and pre-senile dementia. <br /><br />Diagnosis requires a history of harmful alcohol use, and exclusion of other explanations for symptoms (eg diazepam use). Bed-side tests of cognition like the Mini Mental State Examination are usually sufficient, however MMSE is not sensitive to early disease (Manning et al 2007). The Clock test is moderately sensitive and specific and very quick and very cheap! (Pinto and Peters Dement Geriatr Cogn Disord. 2009 27(3):201-13). Formal neuropsychiatric testing is useful to determine functional capacity and in doubtful cases, but is costly, time consuming and difficult to do in this population. Dr Haber considers it is over-ordered. <br /><br />The etiology of alcohol-related cerebellar damage, like Wernicke’s, has a nutritional component, and these syndromes may overlap, or even form a continuum; but unlike Wernicke’s, cerebellar damage evolves subacutely over months & is often not fully reversible. Characteristically, there are wide-based stance and gait, with the legs worse affected than the than arms, while speech and ocular movements are relatively spared. The cerebellum also involved in perception and executive functions and memory, so cerebellar damage may contribute to cognitive deficits. Treatment involves alcohol abstinence, thiamine and multivitamins.<br /><br />Alcohol is associated with stroke by a J-shaped curve, like cardiovascular disease. Moderate consumption lowers stroke risk but there is 4-5 times increased risk at high levels of consumption. Heavy drinking is associated with smoking and with hypertension. Brain haemorrhage (arachnoid, intracranial and subdural) needs to be considered in any confused or obtunded person with a history of harmful alcohol use. A rare but important alcohol-related problem is central pontine myelinolysis, causing quadriparesis and locked in syndrome, when hyponatremia is too rapidly corrected. Diagnosis is confirmed by MRI.<br /><br />Finally, an estimated 50-75% of traumatic brain injury is associated with substance use, but 50% of cases do not present to hospital, and previous brain injury is often overlooked in clinical history and examination. Alcohol use is associated with poorer prognosis and delayed recovery from brain injury which in turn is associated with poor outcomes of alcohol treatment. <br /><br />Indeed, most “talking therapy” is cognitively intensive and may be beyond the capacity of people with alcohol-related brain damage, in terms of reasoning skills, attention skills and memory. One needs either to adapt the program or discontinue it. Rehabilitation services present a particular challenge: the patient who most needs this treatment is least likely to benefit from it.<br /><br /><br />CASE STUDIES: <br /><br />In the second half, three Case Studies of the Bach Siblings were worked through, to show the need to consider a range of causes for collapse, confusion, and ataxia in heavy drinkers.<br /><br />Wilhelm Friedrich Bach, a 58 year old male disability pensioner was brought in to the Emergency Department by ambulance, hypothermic (oral temperature 34) after being found lying supine on the footpath in an inner city street, smelling of alcohol. He had been drinking daily since the age of 25.<br /><br />He was conscious with no neurological deficit but had a deep laceration to his scalp. There were marked hepatomegaly and epigastric tenderness. Haemoglobin was 94 and WBC 13.9 x 109/L. LFTs were consistent with alcoholic hepatitis. Coagulation parameters were normal. Cerebral CT was reported normal. <br /><br />Hypotheses for his collapse included alcohol intoxication, sepsis, myocardial infarction, gastrointestinal bleeding, head injury, seizure, other drug use …. <br /><br />Oral thiamine 100mg bd and alcohol withdrawal scale (AWS) were started, reaching a maximum 7 on the 3rd day of admission. Oral diazepam was given, totalling 20mg, 30mg and 60mg on the first 3 days. On the 4th day the patient showed flat affect, slow speech and had a gross tremor of both hands, and a wide-based ataxic gait. Mini Mental State Examination score was 24/30. The patient was disoriented in time and place with poor performance evident in short term recall, abstract thinking and construction. <br /><br />The differential diagnosis of his ataxia and confusion included cerebellar disease, Wernicke’s and alcohol-related cerebrocortical damage. Review of his cerebral CT showed global atrophy, suggesting the possibility of repeated traumatic injury in the past. <br />2 weeks after admission, his activities of daily living had improved to the point where he was considered suitable for placement in the rehabilitation hostel level. <br /><br /><br />His younger brother, Carl Philip Emmanuel Bach, a 46 year old male on sickness benefits, was brought in by ambulance with a 3 day history of being essentially bed-bound; unable to walk, he had been crawling to the bathroom and showered sitting on the floor. He was currently drinking about 300g-400g alcohol/day, and had been admitted to hospital on several occasions for alcohol withdrawal-related seizures. <br /><br />Hypotheses for his inability to walk included cerebellar disease, Wernicke’s and alcohol-and malnutrition-related muscle wasting. <br /><br />On examination, he had profound truncal and gait ataxia, pronounced scanning dystharthria, and symmetrical vertical and horizontal nystagmus; dysmetria (finger-nose past-pointing), dysdiadochokinesia and heel-shin ataxia. Limb muscle power, tone and reflexes were normal but there were diminished light touch sensation in the hands, and diminished light touch and pin-prick sensation and proprioception in the feet.<br />Investigations: he had negative serology for HIV, and screen for a range of neuronal antibodies was negative; cerebral CT was reported as showing generalised cerebral and cerebellar atrophy. There was no enhancement of the mamillary bodies with contrast (a radiological sign of necrosis at this site in Wernicke's disease). Electromyogram was consistent with moderate-severe peripheral neuropathy. <br /><br />The diagnosis of alcoholic cerebellar degeneration, with severe midline and lateral cerebellar dysfunction, was made. After 4 months in the rehabilitation ward, he remained unsafe walking even with support, and hostel accommodation was required. <br /><br /><br />Ms PDQ Bach, 52 years old, was brought in by ambulance after falling down the stairs at home. She had been drinking daily since the age of 30. She had previously worked as an auditor but had been unable to work for the previous 4 years; she had been lately prone to leaving the house for a walk with the doors and windows wide open and no-one at home.<br /><br />She was conscious and oriented with a Glasgow Coma Scale score of 16. There were marked hepatomegaly and cerebellar ataxia. She was incontinent of urine and faeces. LFTs showed alcoholic hepatitis. Cervical spine and cerebral CTs were normal. <br /><br />The hypotheses for her fall were similar to those for her elder brother. She too was given oral thiamine 100mg and an alcohol withdrawal scale (AWS) was commenced, The AWS peaked at 6 on the 3rd day, and a total of 50mg of diazepam was given on this day, 60mg on the fourth day and the final AWS-determined dose of diazepam at lunch time on day 5, however PRN diazepam continued. <br /><br />On the 6th day, PDQ’s gait remained unsteady and shuffling and she was mildly disoriented and belligerent, with a MMSE score of 23. She did not see why she should stay in hospital, though she could not walk safely, and was still incontinent of urine.<br /><br />Hypotheses for her mental state included Wernicke’s, alcohol-related cerebrocortical damage, and the effects of continuing diazepam. <br /><br />On the 15th day, the patient attempted to leave the hospital, wandering, confused, disoriented, paranoid and agitated. On psychiatric assessment, she was determined to have no perceptual disturbances or evidence of paranoia, but evidence of confabulation. The Mini Mental State Examination score was 21/30 with poor registration and recall, abstract thinking, sentence repetition and design. She was treated with haloperidol 5mg orally, and risperidone to begin 0.5mg orally bd; a 24 hour attendant was arranged under 'duty of care' provisions. <br /><br />Formal neuropsychiatric testing later showed impaired cognition, delayed information recall with inclusion of intrusive and incorrect information, slow psychomotor function, including slow page scanning; reduced awareness and insight; deficits in cognitive and semantic fluency, visuo-spacial and visuo-constructional skills. These were said to be all consistent with alcoholic brain damage: further the memory problems were considered consistent with Korsakoff's syndrome.<br /><br />Nine weeks after admission, the patient was still awaiting suitable placement.<br /><br />In each of these cases, Dr Haber suggested thiamine should ideally have been given parenterally in the emergency department, rather than orally. <br /><br /><br />Written by Richard Hallinan FAChAM based on talk and power point presentation by Prof Paul Haber on Tuesday 20th April 2010 at Concord Hospital as part of the Concord Dependency Seminar Series. <a href="http://dependencyseminars.blogspot.com/">http://dependencyseminars.blogspot.com/</a>Unknownnoreply@blogger.comtag:blogger.com,1999:blog-2135134153424193830.post-83360898901091756582009-12-05T21:07:00.002+11:002010-01-07T02:13:56.512+11:00The GREAT debate - what is the best drug for dependency?Concord Seminar Series – Tues 1st December 2009.<br /><br />Collegial debate: What is the drug of first choice for opioid dependence?<br /><br />In this seminar we had four cases "for the sake of argument" as to what should be the drug of first choice for opioid dependence.<br /><br />Richard Hallinan first argued the case for buprenorphine.<br /><br />The first point is buprenorphine's similar efficacy and cost effectiveness compared with methadone. Systematic reviews show retention in treatment was superior for flexible MMT over flexible BMT dosing but no significant difference in opiate use; overall MMT was slightly more effective and less costly than BMT (Connock et al 2007; Mattick et al 2008, Cochrane).<br /><br />Lower retention may reflect an advantage of buprenorphine, the ease of reductions & withdrawal. Buprenorphine had the highest cost effectiveness for inpatient or outpatient withdrawal management of the modalities examined in the NEPOD studies (Shanahan et al 2006); and the ease of reductions/withdrawal in short term dosing 1-4 weeks is endorsed in a Cochrane review (Gowing et al 2009). Buprenorphine has great flexibility as a "gateway" treatment, whether to abstinence, naltrexone (O’Connor et al 1997; Collins et 2005; Umbricht et 1999), or MMT.<br /><br />The third major point is buprenorphine's greater margin of safety than methadone, reflected in low mortality rates in BMT in France despite liberal availability and unsupervised dosing for a number of years. “Indirect comparison of data from population cross-sectional studies suggests that mortality with BMT may be lower than that with MMT" (Connock et al 2007). In a 10 year longitudinal follow-up of participants in a randomized trial of MMT vs BMT there was no significant difference in mortality by treatment group (Gibson et al 2008). NSW data following up all MMT and BMT starts showed "Despite shorter retention in treatment, buprenorphine maintenance was not associated with higher risk of death." (Bell et al 2009).<br /><br />Buprenorphine has fewer & less severe side effects and drug interactions compared with methadone. QT prolongation is not associated with buprenorphine, and pharmacokinetic interactions are less troublesome, partly because of the wide safety margin of buprenorphine itself. Sexual side effects appear to be lower with buprenorphine. Most importantly, sedation, especially with benzodiazepines, is less. (Lintzeris et al 2006, 2007)<br /><br />A further argument in favour of buprenorphine as first line treatment is that a stepped care model starting with buprenorphine progressing to MMT has been shown to be non-inferior to standard MMT (Kakko et al 2007, 96 self-referred subjects randomised). Outcomes were virtually identical for retention in treatment and proportion of urine samples free of illicit drugs. Among completers of stepped therapy, 46% ultimately remained on buprenorphine/naloxone.<br /><br />A number of RCTs show equivalence of second daily or thrice weekly dosing to daily dosing. Less frequent attendance has greater acceptability to patients, and there is reduced need for take-home or unsupervised doses, reduced risk of diversion, and potentially greater public and political acceptability of this treatment.<br /><br />Finally there is the existence of a formulation of buprenorphine less attractive to injectors, buprenorphine/naloxone. “Most (68%) had tried the buprenorphine +naloxone combination IV, but 80% said they had a "bad" experience. Its street price was less than half that of buprenorphine alone.” (Alho et al 2006). “In the year after its introduction in Australia, BNX was injected less frequently and by fewer regular IDUs and clients compared with BPN” and compared with methadone. (Degenhardt et al 2009, IDRS, 2003-2007, adjusted for sales).<br /><br />RH concluded: "What I am not saying: is that buprenorphine is "better". But why would you NOT choose as first line treatment a medication of similar efficacy and cost effectiveness, greater safety, better side effect profile, lower drug interactions, greater ease of reductions, and greater public acceptability than MMT, which gives equivalent results in a stepped care model to standard MMT? "<br /><br />_________________________________________________<br /><br />Prof Nicholas Lintzeris next argued why sustained release oxycodone (or indeed sustained release morphine, now available in twice daily and even once daily formulations) would be the ideal drug for opioid maintenance treatment. This is admittedly hypothetical since current NSW law only allows oxycodone hydrochloride for pain indications in non-dependent patients except under specific authority from PSB.<br /><br />Prof Nicholas Lintzeris gave the case for oxycodone based on:<br /><br /># Pharmacological principles (sustained delivery, avoiding peaks and troughs, possibly even superior in this respect to methadone which can fluctuate widely within a 24 hour period and sometimes needs twice daily dosing to avoid emergence of withdrawal symptoms).<br /># Side effects (there may be less constipation and sweating than with methadone)<br /># Overcoming demand problems (these medications are already preferred by many, if not most, opioid dependent people, on grounds of greater predictability and safety and lower cost, compared with heroin).<br /># Overcoming supply problems (any doctor can feel comfortable prescribing these medications, as they already do so for pain, provided they adhere to risk management strategies; the risks and difficulties associated with long half life agonists - accumulations and overdose - do not apply).<br /># Stigma (methadone has a stigma which discourages many people from entering maintenance treatments).<br /># Do-it-yourself injectables clinic.<br /><br />There is an existing, albeit limited evidence base regarding the use of slow release oral morphine to treat opioid dependence (e.g. see Mitchell, White et al 2004 - below), demonstrating the such approaches are feasible. In Austria, oral morphine is a licensed and available treatment approach for opioid dependence, and accounts for approximately a third of treatment places. An important step forward however for more widespread uptake of this approach is development of abuse deterrent preparations that reduce the risk of injecting formulations.<br /><br />_____________________________________________________________<br /><br />Richard Hallinan then put the case for naltrexone. Naltrexone is the most direct path to abstinence, the gold standard treatment outcome. It has minimal side effects, no opioid side effects, minimal drug interactions, is non dependency forming, reduces opioid craving, and it’s easy to stop.<br /><br />Naltrexone also has other therapeutic benefits including effectiveness in reducing alcohol consumption (Cochrane standard evidence), effectiveness for weight loss (especially in combination with bupropion) and effectiveness to reduce amphetamine use (Jayaram-Lindstrom et al 2008 RCT n=80, vs placebo).<br /><br />Naltrexone ought to be first line treatment, however currently it is manifestly not so, neither as doctor or patient preference. Low demand and uptake reflects low patient enthusiasm, poor retention, and in Australia the cost, as the treatment is unsubsidised. There are also difficulties of induction, including the high cost of rapid opioid "detoxification" as the preliminary step.<br /><br />There is a lack of RCT evidence supporting oral naltrexone: poor treatment retention, and modest heroin use reduction compared with placebo, which was non-significant with adequate concealment. (Minozzi et al 2006, Cochrane review). There was also greatly elevated overdose risk due to poor treatment retention. “The relative risk of death for oral naltrexone subjects was 7.4 times (high-risk period, p < 0.0001) or 2.8 times (low-risk period, p = 0.055) that of methadone subjects.” (Gibson and Degenhardt 2007, see also Digiusto et al 2004, NEPOD). <br /><br />Naltrexone is safe and effective if people take it. As the problem is compliance with oral naltrexone, naltrexone sustained delivery formulations should be the answer. Unfortunately, large scale use of naltrexone implants began in Australia before preclinical, phase 1, 2 or 3 studies were carried out. Various formulations and devices have been offered in different places, and at different times, with some doubts about uniformity of manufacture and good manufacturing practice accreditation over the years. <br /><br />Even nearly a decade later, the published literature leaves the critical reader in doubt about the rate of serious adverse effects, the efficacy of implants (duration of adequate blood levels and inter-individual variability in blood levels), the risk of problematic use of other substances, and long term outcomes. <br /><br />Retrospective and naturalistic studies for efficacy and safety, however, suggest probably higher safety from implant formulations compared with oral naltrexone, and at least comparable safety (in terms of mortality) compared with MMT and BMT.<br /><br />In Western Australia, naltrexone implant treatment was associated with reduced opiate overdoses compared with pretreatment, but increased sedative and other drug overdoses and other drug related hospital admissions (Hulse et al. 2005, Ngo et al. 2008). In Queensland, a retrospective study from a single treatment centre found lower crude mortality but no significant difference in standardized mortality rate for naltrexone implant compared to BMT (Reece 2007). Similarly Tait et al. (2007) found age standardized mortality rate ratio for naltrexone implant vs MMT to be 0.65 (95% CI = 0.12–1.2 NS). <br /><br />There have been two RCTs of the “GoMedical” naltrexone implant. Kunøe et al 2009 (n=56, 180 days) found lower heroin use, fewer days’ use compared with “normal after care”. Hulse et al 2009 (vs oral Ntx, n=70, 180 days) found lower self reported opiate use, but no difference in urine test confirmed heroin use; other drug use, especially non-heroin opioid use, was poorly assessed. The average duration of adequate blood naltrexone level was substantially revised downwards, compared with previous studies. The good news was that in neither study were there any deaths in patients who received implants. <br /><br />RH concluded: "What I am not saying is that naltrexone is 'better'. But everyone deserves a chance at abstinence before being committed to agonist therapy, which leaves patients physically dependent on opioids with their considerable side effects, as well as being subjected to intrusions and restrictions on their lives, which may be for many years with no good evidence for how to end the treatment. The future of naltrexone treatment for opioid dependence must be sustained release naltrexone preparations."<br /><br />____________________________________________________<br /><br />Andrew Byrne, Redfern Surgery. <br /><br />Methadone is the drug of choice for opioid dependence. Forty years of research prove that this therapy is effective in retaining patients in treatment, reducing illicit drugs use, lowering viral transmission and eliminating almost 80% of overdose deaths. None of these benefits has been shown to the same degree for buprenorphine and thus it should not be recommended as first line drug unless there are contraindications for methadone. Further benefits for those taking methadone is that it is safe in pregnancy and lactation while it is also more widely available both in Australia and around the world. <br /><br />A possible increase in the overdose rate in the first two weeks of treatment is balanced by high numbers of drop-outs in the first two weeks of buprenorphine treatment. A recent large study in Norway showed two deaths in the first month of treatment out of over 3000 episodes in a seven year period. <br /><br />However, patients make the choice about which drug much more often than doctors do (see below). <br /><br />Cost effectiveness is far more positive with methadone, being an inexpensive non-patented drug. Common side effects are limited to constipation and sweating. More serious side effects can be limited by dose adjustments and hormone replacement when testosterone levels are suppressed. QT prolongation is common but appears to be of no clinical significance in isolation. Torsade de pointes tachycardia has only been associated with multiple risk factors some of which coincide with long-term survivors of opioid use, prescribed medications, alcohol and illicit drug use. Methadone has not been demonstrated to cause torsade and it is possible that higher doses make this less likely to occur. It is generally agreed that as with other drugs having a dose response, there should be no arbitrary limit on methadone dose levels. <br /><br />Some references were detailed for the Concord audience. <br /><br />RCT buprenorphine/methadone.<br /><br /> Ling W, Charuvastra C et al. <br /> Mattick RP, Ali R, White JM et al.<br /> Kristensen O, Espegren O et al.<br /> Kakko J, Grönbladh L, Svanborg KD et al. <br /> Pinto H, Rumball D et al. <br /> Kamien JB, Branstetter SA, Amass L. <br /> Petitjean S, Stohler R, Déglon JJ et al. <br /> Cochrane Database of Systematic Reviews<br /><br />Reasons for choosing MMT.<br /> Cost (cheapest drug around)<br /> Safe in pregnancy<br /> Available most widely (Aussie pts travel!)<br /> Highest retention rate<br /> Lowest illicit drug use rates<br /> Safety when used under supervision<br /> Original and best known. <br /><br />How many patients have already tried both methadone and buprenorphine? It seems that the majority of patients attending for opioid dependency treatment are now aware of both methadone and buprenorphine and most have a clear idea which is best for them. This is due to personal trial and error or else street talk of the properties of both. But is this all hypothetical? Doctors are in fact only rarely in a position to decide/advise between methadone and buprenorphine. <br /><br />English GP study <br /> A pilot study for a randomized controlled and patient preference trial of buprenorphine versus methadone maintenance treatment in the management of opiate dependent patients. Dr Pinto in England was trying to prove that buprenorphine had benefits worth including on the NHS formulary for their area. Out of 42 subjects recruited, none agreed to be randomized. The reason was that all patients had a clear idea which drug they wanted and refused to consider alternatives in this trial setting. <br />Pinto H, Rumball D, et al. Journal of Substance Use 2008 13;2:73-82<br /><br />World’s largest study on OTP.<br /> Burns L, Randall D, Hall WD, Law M, Butler T, Bell J, Degenhardt L. Opioid agonist pharmacotherapy in New South Wales from 1985 to 2006: patient characteristics and patterns and predictors of treatment retention. Addiction 2009 104;8:1363-1372<br /><br />Burns et al. abstract quotes:<br /><br /> “the hazard of leaving treatment was 1.9 times for those on buprenorphine relative to those on methadone”<br /> “This study has provided population-level evidence to suggest that retention in methadone and buprenorphine differ in routine clinical practice.” (retention in methadone was much better). <br /><br /><br />Things go better with methadone! <br /><br /> Much lower diversion rates (anecdotally)<br /> No substantial problems with contaminated drug being injected (unlike buprenorphine). <br /> Less “revolving door” syndrome as with buprenorphine (see Burns’ latest study). <br /><br />Best drug for addiction Rx.<br /> Do you want your patient to have the best chances of getting their lives together, staying in treatment and avoiding illicit drugs? <br /> Of course you do! <br /> Then you should recommend methadone as a first option when there is a choice. <br /><br />Is this debate “for real”? <br /> Would we be having this debate about antibiotics, antidepressants or hypertension drugs? <br /> Of course not! <br /> **Treatment matching** is the way to go. [Which brings us to the case studies presented in the second half (see below)] <br /> Dependency medicine has a way to go, too! <br /><br />_______________________________________________________<br /><br />Post Script<br /><br />RH introduced several intentional errors/dubious claims in his presentations, some of which were identified by participants, and others swallowed whole, perhaps owing to the poker faced delivery. <br /><br />There is no good evidence that naltrexone reduces opioid craving. <br />Evidence that sexual side effects are lower with buprenorphine is weak, and there is no research for women.<br />Second daily or thrice weekly buprenorphine dosing in clinical practice seems to suits only a minority. <br />Naltrexone alone, without bupropion, has small effectiveness for weight loss. <br />RCT evidence does not support claims for greater safety for buprenorphine (but as NL pointed out, safety for 3rd parties, especially children, is certainly greater for buprenorphine). <br />There is no evidence that reductions over a longer period are easier for buprenorphine than methadone, and 2 studies sometimes cited to support the claim short term ease of buprenorphine reductions compared with methadone compared a buprenorphine + carbamazepine regime to an methadone + carbamazepine regime. Carbamazepine is a powerful inducer of the metabolism of methadone. (Seifert et al 2002, 2005)<br /><br />_________________________________________________<br /><br /><br />Concord Dependency Seminar November 2009, Treatment Matching - Case Studies<br /><br />Kyle, a 19 yo heroin user, has been smoking heroin since age 16, daily for the last year, and recently he started injecting it. He used MDMA on weekends from age 16, seldom drinks alcohol or smokes THC, but smokes cigarettes. He has previously "dried out" several times using his mother’s Serepax, but stayed clean for only 3-10 days. He is a student at uni doing arts/law, and lives with his parents. He has maxed out credit card, has stolen money from his parents, used up all a private inheritance from his grandfather who died 3 years ago ($40,000).<br /><br />Kyle feels he has lost control. He badly needs money, and feels he may have to work as a prostitute. He doesn’t want anyone to know he is using heroin, and is terrified his step-father (a public prosecutor) will find out. He can’t go away or do a rehab for this reason, and anyway he is in the middle of term with exams in 6 weeks. He asks for medications so he won’t have to use heroin.<br /><br />What treatment is first choice for Kyle?<br /><br />Comments: a show of hands gave majority support for buprenorphine for this patient, owing to his current predicament, and the short duration of his opioid dependence. He might use buprenorphine for withdrawal management and go onto maintenance if needed. Ross Colquhoun (who will present his experience with naltrexone implants in the Feb 2010 Concord seminar) felt this patient would do very well with naltrexone implant, but this would be too disruptive currently and he should be stabilised on buprenorphine first. Cost would probably also be a major problem. <br /><br />_______________________________________________<br /><br /><br />Robbie is 41 yo, and has been a disability pensioner for 15 years for "mental health problems", including psychosis. He has been an involuntary inpatient for extended periods, including 6 months last year, and his community treatment order has ended. He is no longer getting depot flupenthixol. Two recent hospital admissions under the mental heath act were for aggression/violence. He comes asking for treatment because he has been hanging out, says he has been using $200/day of heroin (he says he has a neighbour who is a dealer). He says he was on MMT once before for 18 months but didn’t like it. Sometime he does inject BM methadone.<br /><br />On examination he is in classic opioid withdrawal, and has plenty of old scars and recent tracks.<br /><br />A call to the local mental health service confirms his psychotic episodes have often been precipitated by alcohol or, apparently, amphetamines. He also uses benzodiazepines and cannabis, according to previous history and urine toxicology. <br /><br />What treatment is first choice for Robbie?<br /><br />Comments: a show of hands gave majority support for methadone for this patient, owing to his psychotic illness and the antipsychotic properties of methadone. Retention in treatment might be an issue with buprenorphine given his previous poor compliance with antipsychotics. However, doubt was cast on the history of heroin use, as it seems unlikely a long standing disability pensioner for "mental health problems" would have the capacity and resources to afford $200/day. Induction onto methadone would have to be very cautious. It was noted that amphetamine intoxication could potentially be confused with opioid withdrawal. Naltrexone treatment was generally considered inappropriate. <br /><br />_______________________________________________<br /><br /><br />Emma is 36, and a business analyst working for a merchant bank. She is single, works hard and plays hard, and loves having the freedom to party. But partying has got a bit out of control. She admits to near daily drinking (60-90g/day for several years), & occasional use of cocaine on the weekends. There is also frequent use of over-the-counter and prescribed codeine (40-120mg/day) and oral amphetamines as a "pick me up" during the week. <br /><br />3 months ago Emma was introduced to heroin. She has recently injected it a few times and now is afraid she might be getting a habit. She wakes up craving heroin, can’t get it off her mind, and uses codeine to get through the day. She finds heroin really helps with her severe period pains and wonders about getting a hysterectomy. The heroin use worries her because she doesn’t want to be addicted. She despises junkies and is appalled by the idea of methadone.<br /><br />What treatment is first choice for Emma?<br /><br />Comments: the majority view was that alcohol was her primary problem, and her other drug problems (use of codeine and amphetamines for hangover) might be more easily controlled if she could achieve alcohol abstinence. An inpatient opioid/alcohol withdrawal management and a period of residential rehabilitation, or intensive outpatient counseling supported by alcohol pharmacotherapy would be the best option if she were prepared to try it. <br /><br />However, if opioid maintenance was needed, a show of hands gave majority support for buprenorphine for this patient, owing to her resistance to methadone and the possibility that alcohol use might be less problematic if she were on a partial agonist. However the gynaecological problems need assessment and management, and her chronic pain might make a full opioid agonist necessary. NL argued that this is exactly the sort of patient who would do well with supervised dosing of a sustained release opioid such as oxycodone, which might be justified for her chronic pain, and which she would probably find more acceptable than methadone or buprenorphine. Ross Colquhoun felt this patient would do very well with naltrexone implant, which would also help with her alcohol problem. <br /><br /><br />Ref 1. <br />Mitchell TB, White JM, Somogyi AA, Bochner F. Slow-release oral morphine versus methadone: a crossover comparison of patient outcomes and acceptability as maintenance pharmacotherapies for opioid dependence. Addiction. 2004; 99:940-5Unknownnoreply@blogger.comtag:blogger.com,1999:blog-2135134153424193830.post-88798032368814101212009-08-08T19:53:00.004+10:002010-02-04T01:26:10.458+11:00Alcohol dependence - an update for medical interventions.Concord Seminar Tuesday 4th August 2009. <br /><br />Mechanisms and Treatment of Alcohol Dependence and its Sequelae: a 2009 Update<br /><br />Dr Saunders used a single, complex case of alcohol dependence to introduce an overview of neurobiological mechanisms underlying the development of dependence; and a case of fetal alcohol syndrome, as an example of alcohol related neurodegeneration. <br /><br />Patient K was a woman in her early 40s who had lost a promising professional career and marriage in her late 20s after a severe neurological insult left her with cognitive impairment, gait disturbance and dysarthria. Five years later she had married again and entered into a new phase of life, but gradually developed alcohol dependence with regular consumption of 120-180g/day. Among risk factors were a family history (father) of alcoholism, and the trauma and loss resulting from her disability and possibly also the brain injury itself. Treatment followed a not unusual course of withdrawal management followed by periods of abstinence supported by acamprosate and/or naltrexone, each time with subsequent relapse. <br /><br />Twin studies show about 50% of population variance of alcoholism to be genetic; there is a tendency to father-son and mother-daughter vectors. Cohort longitudinal studies point to developmental factors especially childhood abuse, be it physical, sexual, or repeated mental abuse, along with other trauma, for example PTSD. At a sociological / anthropological level, cultural, socioeconomic and regulatory factors are also important. <br /><br />What are the mechanisms of dependence? While workers in the field of addiction are becoming fairly familiar with the idea of meso-limbic reward pathways, our speaker gave us a more comprehensive understanding of the neurobiological mechanisms of dependence by including also mesolimbic stress, and frontal inhibitory, control systems. <br /><br />Among the neuronal reward circuits, dopaminergic pathways are especially important for psychostimulants and nicotine, and opioid pathways for alcohol and opioids. When such substances are repeatedly or continuously used, the natural activity of these systems is suppressed. A negative mood and motivational state develops: more and more of the substance is required merely to maintain the normal state, while other normally "rewarding" activities become blunted. The substance use can be said to have “high-jacked” the reward system. <br /><br />At the same time, with repeated substance use the balance is re-set between brain stress and anti-stress systems, through stimulation of pathways involving the excitatory neurotransmitter glutamate and CRF (corticotrophin-releasing factor) and suppression of GABA and ‘Neuropeptide Y’ circuits. The stress systems become “supercharged” to respond to exposure to psychoactive substances and cues or trigger for the substance use. <br /><br />Finally, with repeated substance use there is progressive impairment of pre-frontal-mesolimbic inhibitory pathways, with impairment of executive functioning, decision-making and insight.<br /><br />In combination, suppression of reward systems, their "high-jacking” by substance use, and “supercharging” of the stress systems to respond to psychoactive substances and their associated cues, generate a powerful “internal driving force” which is little influenced by voluntary control, because of impaired frontal inhibitory systems. <br /><br />At this Concord Seminar, when an audience member asked about the situational and emotional triggers for alcohol use in patient K, Dr Saunders responded: "It doesn't matter what the triggers are, she is dependent. There is an overwhelming, tsunami-like force driving it." <br /><br />Pharmacotherapies for alcohol dependence, included much the same list as when Dr Saunders last spoke to us in 2005, though the evidence base has developed since then. <br /><br /> Naltrexone (blocks opioid pathways for alcohol reinforcement/reward; see below)<br /> Acamprosate (restores balance to GABAergic/glutaminergic stress responses; see below)<br /> Topiramate (similarly, restoring balance to GABAergic/glutaminergic pathways in the corticomesolimbic system; several randomised trials from USA, and Finland)<br /> Disulfiram (aversive agent, unpleasant reaction on alcohol ingestion; see below)<br /> Ondansetron (selective 5-HT(3) (serotonin) antagonist [‘Zofran’] may be effective for patients with early-onset alcoholism, associated with greater serotonergic abnormality & greater mood disturbance, including depression, anxiety, hostility and antisocial behaviors)<br /> Baclofen (GABA-B receptor agonist, reducing craving and alcohol intake in small trials)<br /> Buspirone (for alcohol dependence and comorbid social anxiety)<br /> SSRIs (for underlying or residual depression, and to be avoided in young alcoholic men with depression/suicidality, in whom they may make matters worse – the reason for this is not entirely clear, but see ondansetron above)<br /><br />While a Cochrane review (Srisurapanont et al, 2005) for naltrexone gives clear evidence that relapse into alcohol dependence is reduced by some 36%, the Cochrane review of acamprosate has not yet reported, and there have been negative findings from recent US and Australian studies. There have been two important studies of combined naltrexone and acamprosate for alcohol dependence, with some evidence of benefit from the combination in Kiefer et al (2003) but little at all for acamprosate from the COMBINE Study (eg Anton et al 2006; Donovan et al 2008). There is also good evidence for improved outcomes for disulfiram, provided it is supervised. <br /><br />With huge variability in findings from different studies, especially for acamprosate, Dr Saunders notes that exploring the heterogeneity of these studies may be a key for furthering our understanding and planning further research. Much may be lost by the reductionism of meta-analysis. Meanwhile, naltrexone tends to be his first line choice for alcohol dependence. <br /><br />Some basic contrasts between the use of naltrexone and acamprosate are listed here.<br /><br />Initiation: for naltrexone, when abstinent or when drinking; for acamprosate only when abstinent. <br />Onset of action: for naltrexone within 24 hours; for acamprosate one week<br />Pattern of drinking: for naltrexone, alcohol dependence with binge pattern; for acamprosate, alcohol dependence with regular daily drinking<br />Triggers to drink: for naltrexone, smell, taste, initial consumption of alcohol; for acamprosate, geographical, interpersonal and emotional triggers<br />Sub-type of dependence: for naltrexone, early onset & strong family history; for acamprosate, later onset. <br />Genetic markers: for naltrexone, having opioid receptor gene (OPMR1- Asp40 allele)<br /><br />_______________________________<br /><br />We were then introduced to a difficult clinical situation. An addiction specialist noticed by chance, while treating a pregnant alcoholic woman abstinent in early recovery, that a previous child had previously unrecognised fetal alcohol syndrome. Ethical issues about contacting that child’s doctor, or community services, the potentially devastating impact of informing this woman at such a time and almost certainly precipitating relapse and worse outcomes led to lively discussion. Happily in this case the fine line was successfully trod. <br /><br />Fetal Alcohol Syndrome is at the most severe end of the range of Fetal Alcohol Disorder Spectrum (FASD). The features are <br />1. maldevelopment of the mid face, including a small flattened nose, wide-set eyes, epicanthic folds, a thin upper lip, and absent philtrum<br />2. microcephaly, mental retardation (average IQ 70) and behavioural abnormalities<br />3. congenital cardiac abnormalities<br /><br />Learning difficulties become apparent in childhood, and there is no improvement in IQ over time. There are social interaction deficits, but more typically the children are over-friendly to peers and adults, and so-called moral deficits – high prevalence of promiscuity, sexually transmitted diseases in teen years - may be attributable to these factors.<br /><br />Management consists of teaching adaptive living skills, (such as to be appropriately guarded with strangers and certain family members), educational placement, speech and language services, occupational therapy and vocational guidance, and advocacy as needed.<br /><br />This brought us to the matter of alcohol and neurodegeneration, especially in young people. We are reminded that brain development continues until at least the age of 21. Particularly that during this time, but also afterwards, neurones and their connections are in a state of dynamic flux, of which ongoing neurogenesis is an essential part.<br /><br /> In experimental animals, with increasing alcohol exposure there is increased differentiation of neural stem cells to oligodendrocytes and astrocytes and reduced differentiation to neurones, with blunting of dendrites, and inhibition of neurogenesis as a primary mechanism of neurodegeneration. In Fetal Alcohol Syndrome there is not only major structural damage in the 1st trimester but a quantitative decline in the number of neurones in the 3rd trimester through inhibition of neurogenesis (in which tobacco smoking, diet and vitamin deficiencies probably also play a role). <br /><br /><br />For further reading, we recommend Bankole Johnson's review: <br /><br />Johnson BA. Update on neuropharmacological treatments for alcoholism: scientific basis and clinical findings.Biochem Pharmacol. 2008 Jan 1;75(1):34-56. Full text available free at <a href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=17880925">http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=17880925</a> <br /><br /><br />Also, Dr Saunders won't mind us giving a plug for a new "concise and practical guide for students and practitioners of medicine and other health professions who come into contact with people with substance use disorders." Addiction Medicine. Editors Noeline Latt, Katherine Conigrave, Jane Marshall, John Saunders, E. Jane Marshall and David Nutt. Oxford University Press. ISBN13: 9780199539338Unknownnoreply@blogger.comtag:blogger.com,1999:blog-2135134153424193830.post-56672263190343604742009-03-07T13:49:00.000+11:002009-03-09T03:20:59.600+11:00"Opioid Side Effects - Should we be bothered?"Concord Seminar Tues 3rd February: "Opioid Side Effects - Part 2".<br /><br />Professor Nick Lintzeris gave us a tour through the research on methadone side effects, pointing out the major deficiencies in the methodology of just about every study. There is so little good research on the most common side effects, sweating and constipation, that he decided to omit them altogether. [We had a previous talk on these subjects at Concord and generic advice seems to apply: eg. diet, exercise, dose adjustments, etc.] The other major side effects raised by our speaker were hormonal imbalance, osteoporosis, sleep apnea, cognition and cardiac rhythm disturbances.<br /><br />To put the issue into perspective, we were told that the broad outcomes from buprenorphine and methadone were similar but with (1) significantly better retention for methadone (= fewer drop-outs) but (2) fewer reported side effects for buprenorphine. There was also a trend for less heroin use in methadone versus buprenorphine prescribed patients.<br /><br />The relative merits of the two licensed drugs for opioid maintenance may be less relevant today when most patients have a clear preference before coming into treatment. A major influence on this decision was the patient’s side effects from one drug or the other. Such matters were emphasised by an interesting ‘7 Boroughs’ study from the Maudsley (London) in which our speaker was an author (n=182). Another trial of new patients going onto maintenance treatments in England found that there was not one volunteer in a year who agreed to be randomised to one of these two drugs (Ref 1). They all knew what they wanted from experience.<br /><br />An intriguing power point slide summarized results from a trial from Malaysia showing high rates (30-50%) of urinary hesitancy, constipation, drowsiness and sweating from buprenorphine (Schottenfeld et al). In practice these are rarely seen in the Australian context and one wonders if, like Fanoe’s study on syncope the responses were exaggerated by the nature of the questions, questioning or questioners (or the translation). Fanoe uniquely found 10-30% syncope histories in buprenorphine/methadone patients in Denmark.<br /><br />Regarding endocrine abnormalities it was pointed out that all opioids affect the hypothalamic and peripheral hormone systems, most notably testosterone in men on methadone. Long periods of low testosterone can lead to altered calcium metabolism, osteopenia and in the longer term, osteoporosis. Two studies were quoted showing high rates of both lack of libido as well as erectile dysfunction in men on methadone (more so than with buprenorphine). We were told that depression, pain and fatigue can result from the low testosterone as well as sexual disturbances. One study showed major hypogonadism in buprenorphine patients, (Colemeco), something which is not consistent with other experience. Another study (Kim et al.) showed high rates of established osteoporosis and osteopenia in long term methadone patients. The roles of testosterone replacement, oestrogen, calcium and vitamin D were discussed briefly.<br /><br />There seemed to be a consensus that a one-off measurement of total testosterone (morning specimen is best) was a reasonable measure for all men on methadone. More detailed examinations were justified when there were suspect symptoms (eg. prolactin, oestrogen, thyroxine, etc). Investigation for osteoporosis was more contentious, as for testosterone replacement therapy which has various guidelines, recommendations and PBS prescribing rules. An endocrine opinion can be very helpful in such cases.<br /><br />Sleep apnea has been presented as a looming problem at conferences recently. One small study showed quite worrying results from Weston Hospital in Melbourne. Fatigue and snoring may be the only signs yet sleep studies may show major disturbances including low oxygen and high CO2 levels for extended periods. As with other studies, major methodological problems occur commonly but it was proposed that some otherwise unexplained deaths in methadone patients may be due to sleep apnea. However, as with QT problems, unexplained deaths in methadone/bup patients are exceedingly rare.<br /><br />Professor Lintzeris then handed out a copy of a journal reprint to all participants. We may have been caught out by chronology since his information implied that these were official American guidelines to address cardiac safety in methadone maintenance treatment. Since December, however, this rather contentious article has been withdrawn and republished in at least two more ‘internet’ versions by the Annals of Internal Medicine. Krantz and colleagues recommended ECGs on all patients before treatment and at 3 months and annually despite most experts (including Krantz himself in 2006) saying that routine ECGs were not needed. The recommendation does not have the official backing of CSAT (the official American health authority in this area). More embarrassing still for the authors, a number of expert contributors ‘declined to be acknowledged’ in the final paper, nor were some major potential conflicts of interest declared until the third version.<br /><br />This unusual publication story is now neatly balanced in an excellent editorial by Gourevitch from New York (Ref 2). In it he notes that torsade de pointes tachycardia is rare and typically associated with ‘exceptionally high doses of methadone’ and/or other risk factors for dysrhythmia. He says that more information is needed before cardiographs could be recommended as a safety strategy, favouring as he does an approach based on individualised clinical assessments, just as would be done for any other rare but potential serious complication.<br /><br />Consistent with long standing NSW Health Department policy, those on high doses (>150mg daily) as well as those with other risk factors (HIV, co-medication, >40 years, female sex) should be considered for baseline ECG. Alcohol and cocaine are also strongly implicated in some reports. Of almost 80 torsade cases in the literature I could find only one single death (a female patient aged 47 who had a myocardial infarction and torsade arrhythmia). It still appears that this cardiac complication is either rare or non-existent in young people starting on standard methadone treatment programs.<br /><br />Professor Lintzeris’ title slide stated: “Side effects to methadone: should we be bothered?” The side effects from street drug use are so legion that it is may be easy to overlook unwanted consequences of effective treatment. But this is not what good medicine is all about.<br /><br />Comments by Andrew Byrne based on the Concord Seminar talk, power point slides and pooled references with contributions from Richard Hallinan and Judith Meldrum with thanks.<br /><br />References:<br /><br />1. Pinto H, Rumball D, Maskrey V, Holland R. A pilot study for a randomized controlled and patient preference trial of buprenorphine versus methadone maintenance treatment in the management of opiate dependent patients. Journal of Substance Use 2008 13;2:73-82<br /><br />2. Gourevitch MN. First Do No Harm ... Reduction? Annals of Internal Medicine 2009 150;6 (Annals on line <a href="http://www.annals.org/cgi/content/full/0000605-200903170-00111v1">http://www.annals.org/cgi/content/full/0000605-200903170-00111v1</a> )<br /><br /><br />Clinic web page: <a href="http://www.redfernclinic.com/#news">http://www.redfernclinic.com/#news</a>Unknownnoreply@blogger.comtag:blogger.com,1999:blog-2135134153424193830.post-82007008522614410532008-12-29T17:27:00.000+11:002009-12-23T09:23:09.414+11:00Seminar topics for 2009. Tuesdays at 6.30 for 7pm in Conference Room One, Concord Hospital.3/02/2009 Opioid Side Effects - Part 2. Nicholas Lintzeris<br />7/04/2009 Smoking cessation update. Renee Bittoun<br />2/06/2009 TBA (cancelled)<br />4/08/2009 Alcohol problems. John Saunders<br />6/10/2009 Prescription opioids in chronic pain. Dr Alex Wodak & Dr Milton Cohen<br />1/12/2009 "The great debate" What is drug of first choice in opioid addiction? Dr Nick Lintzeris says oxycodone; Dr Richard Hallinan says buprenorphine; Dr Andrew Byrne says methadone.<br /><br />ARCHIVE OF SUMMARIES (OTHERS SEARCHABLE ON SITE)<br /><br />"Opioid Side Effects - Should we be bothered?"<br /><a href="http://www.redfernclinic.com/concord/2009/03/concord-seminar-tues-3rd-february.php4">http://www.redfernclinic.com/concord/2009/03/concord-seminar-tues-3rd-february.php4</a><br />3/2/09<br /><br />Comparisons from UK, Victoria and NSW. <a href="http://www.redfernclinic.com/concord/2008/02/comparisons-from-uk-victoria-and-nsw.php4">http://www.redfernclinic.com/concord/2008/02/comparisons-from-uk-victoria-and-nsw.php4</a><br />5/2/08<br /><br />Practising in Addiction Medicine: how not to be sued!<a href="http://www.redfernclinic.com/concord/2008/03/subject-practising-in-addiction.php4">http://www.redfernclinic.com/concord/2008/03/subject-practising-in-addiction.php4</a><br />18/3/08<br /><br />Treating the Addicted Brain: Agonists, Antagonists and Modulators. <a href="http://www.redfernclinic.com/concord/2008/05/treating-addicted-brain-agonists.php4">http://www.redfernclinic.com/concord/2008/05/treating-addicted-brain-agonists.php4</a><br />20/5/08<br /><br />Adult ADHD & Substance Use Disorders – Dr Julian Trollor<br /><a href="http://www.redfernclinic.com/concord/2008/07/adult-adhd-substance-use-disorders-dr.php4">http://www.redfernclinic.com/concord/2008/07/adult-adhd-substance-use-disorders-dr.php4</a><br />22/7/08<br /><br />Amphetamine/Stimulant Use: Presentations, complications, interventions.<br /><a href="http://www.redfernclinic.com/concord/2007/01/amphetaminestimulant-use-presentations_30.php4">http://www.redfernclinic.com/concord/2007/01/amphetaminestimulant-use-presentations_30.php4</a><br />30/1/07<br /><br />Methadone side effects, separating fact and fiction.<br /><a href="http://www.redfernclinic.com/concord/2008/03/methadone-side-effects-separating-fact.php4">http://www.redfernclinic.com/concord/2008/03/methadone-side-effects-separating-fact.php4</a><br />20/3/07<br /><br />The Interpretation of Urine Toxicology in Dependency Treatment. Principals and Pitfalls.<br /><a href="http://www.redfernclinic.com/concord/2007/05/interpretation-of-urine-toxicology-in.php4">http://www.redfernclinic.com/concord/2007/05/interpretation-of-urine-toxicology-in.php4</a><br />22/5/07<br /><br />Personality Disorders. 31 July 2007<br /><a href="http://www.redfernclinic.com/concord/2007/07/personality-disorders-31-july-2007.php4">http://www.redfernclinic.com/concord/2007/07/personality-disorders-31-july-2007.php4</a><br />31/7/07<br /><br />Personality disorders (by Dr Glenys Dore) supplementary notes.<br /><a href="http://www.redfernclinic.com/concord/2008/07/personality-disorders-by-dr-glenys-dore.php4">http://www.redfernclinic.com/concord/2008/07/personality-disorders-by-dr-glenys-dore.php4</a><br />31/7/07<br /><br />Withdrawal management and detoxification-with a focus on complicated patients.<br /><a href="http://www.redfernclinic.com/concord/2007/09/withdrawal-management-and.php4">http://www.redfernclinic.com/concord/2007/09/withdrawal-management-and.php4</a><br />25/9/07<br /><br />Advances in assessment and treatments for infection with hepatitis C virus (HCV)<br /><a href="http://www.redfernclinic.com/concord/2007/11/advances-in-assessment-and-treatments.php4">http://www.redfernclinic.com/concord/2007/11/advances-in-assessment-and-treatments.php4</a><br />20/11/07<br /><br />Welfare to Work, Implications for your Patients.<br /><a href="http://www.redfernclinic.com/c/2006/06/welfare-to-work-implications-for-your_2495.php4">http://www.redfernclinic.com/c/2006/06/welfare-to-work-implications-for-your_2495.php4</a><br />30/5/06<br /><br />Dependency issues and pain management - "A Busman's Holiday and Other Stories" <a href="http://www.redfernclinic.com/c/2006/08/dependency-issues-and-pain-management_9514.php4">http://www.redfernclinic.com/c/2006/08/dependency-issues-and-pain-management_9514.php4</a><br />25/7/06<br /><br />Opioid Maintenance: Back to Basics. Therapeutic lessons from Vioxx and LAAM.<br /><a href="http://www.redfernclinic.com/c/2006/11/opioid-maintenance-back-to-basics_9619.php4">http://www.redfernclinic.com/c/2006/11/opioid-maintenance-back-to-basics_9619.php4</a><br />26/9/06<br /><br />Dependency issues in gaols, juvenile justice and drug courts <a href="http://www.redfernclinic.com/c/2006/11/dependency-issues-in-gaols-juvenile_7874.php4">http://www.redfernclinic.com/c/2006/11/dependency-issues-in-gaols-juvenile_7874.php4</a><br />21/11/06<br /><br />The use of anti-craving drugs for alcohol dependence.<br /><a href="http://www.redfernclinic.com/concord/2008/02/use-of-anti-craving-drugs-for-alcohol.php4">http://www.redfernclinic.com/concord/2008/02/use-of-anti-craving-drugs-for-alcohol.php4</a><br />4/2/03<br /><br />Dental problems in addiction treatment subjects. Does methadone rot teeth? Can we prevent dental decay?<br /><a href="http://www.redfernclinic.com/c/2003/05/dental-problems-in-addiction-treatment_20.php4">http://www.redfernclinic.com/c/2003/05/dental-problems-in-addiction-treatment_20.php4</a><br />20/5/03<br /><br />Smoking cessation in dependency patients / Therapeutic thresholds in methadone maintenance<br /><a href="http://www.redfernclinic.com/c/2003/09/smoking-cessation-in-dependency_23.php4">http://www.redfernclinic.com/c/2003/09/smoking-cessation-in-dependency_23.php4</a><br />23/9/03Unknownnoreply@blogger.comtag:blogger.com,1999:blog-2135134153424193830.post-56317981261149651102008-07-31T00:47:00.001+10:002010-01-12T01:09:05.519+11:00"The Other Hepatitis" - An Update on Hepatitis B.Concord Dependency Seminar Tuesday 23 July 2008 "The Other Hepatitis" - An Update on Hepatitis B. Dr Gail Matthews, St Vincents Hospital Darlinghurst <br /><br />Summary Part 1. Epidemiology, natural history, assessment. <br /><br /><br />This seminar was titled The Other Hepatitis, reflecting the lower prevalence of Hepatitis B compared with Hepatitis C among people using addiction treatment services, and the lower profile of HBV in the community.<br /><br />In contrast to the vigorous response in recent years to hepatitis C (HCV) in Australia, the response to hepatitis B (HBV) has lagged behind, despite important recent developments in understanding of HBV, in diagnostic tests and antiviral treatments, and desite its large disease burden, especially chronic liver disease and liver cancer. <br /><br />There are many contrasts between HBV and HCV. Whereas HCV in Australia consists of two 'epidemics' - an older group of people born overseas in endemic areas and a younger group of injecting drug users - about half the prevalence of HBV is among Australians born overseas in endemic areas, especially China and SE Asia but also the Middle east and Mediterranean. Only 5% of chronic HBV is among IDUs; another 8% among men who have sex with men (MSM) and a staggering 16% among indigenous Australians. <br /><br />The picture is different for new infections (incidence) of HBV in Australia: 44% of these happen among IDU (showing the importance of catch-up vaccination for non-immune people in this risk group) and 35% are through sexual transmission, disproportionately among MSM, but the majority still through heterosexual sex.<br /><br />The total number of people in Australia with chronic HCV is fairly reliably estimated to be between 200,000 and 250,000, while estimates for HBV range more widely between 90,000 and 160,000, reflecting in part poor knowledge of HBV and low levels of testing among some of the high risk groups. <br /><br />HBV is a DNA virus, where HCV is an RNA virus. HCV is essentially blood-to-blood transmission, particularly by unsafe injecting, and rarely by sexual transmission, while HBV is spread by contact with infected body fluids including blood, semen and saliva. HBV is thus sexually transmitted, but also by vertical transmission (mother to child), horizontally (close personal contact especially in childhood eg cuts, sores) and by IDU. <br /><br />Of people infected with HCV, 20-30% spontaneously clear the virus, usually within 6 months, and regardless of their age at infection, without however developing immunity (ie they can be reinfected with HCV). Few people develop clinically evident acute hepatitis. By contrast, for HBV progression to chronic infection is strongly related to age at infection: 80-90% of children infected perinatally develop chronic HBV, with lower rates (30%) of chronicity after infection under the age of 5 years; only 6% of older children and adults develop chronic HBV. Most adults who are infected with HBV develop clinically evident acute hepatitis. <br /><br />Unlike HCV where late clearance of the virus is unknown, a small percentage of people with chronic HBV clear the virus and develop immunity each year.<br /><br />HBV and HVC are similar in that a subset of people develop chronic liver inflammation which may slowly progress to cirrhosis and liver failure in a minority of cases, and which increases the risk of development of hepatocellular carcinoma (HCC). <br /><br />The diagnostic tests for HBV, and the natural history of the disease, while rather more complicated than for HCV, have become clearer in recent years. Chronic HBV is now though of as having 4 phases, with gradual progression through the first 2 phases "immune tolerant" and "immunoactive" into the third phase called "immune control" and sometimes progression into a fourth phase called "immune escape". <br /><br />In the "immune tolerant" phase, there are high levels of HBV-DNA in the blood but little inflammation of the liver (so liver enzymes like ALT are low or normal). The body is not really fighting the virus. This phase is prolonged in people who get HBV perinatally (20 years or more) but is usually much shorter in adult infections. <br /><br />In the "immunoactive" phase, DNA levels and liver inflammation (ALT) tend to fluctuate. The body is fighting the virus and the liver is in the wars. This can go on for many years, and this is when much of the liver damage from HBV develops. <br /><br />If the body develops "immune control", viral DNA drops to undetectable levels and the liver function tests normalise. This phase can go on for decades and is associated with no progression of liver disease. <br /><br />Unfortunately in some people HBV escapes from immune control. In the "immune escape" phase, viral DNA is detectable again and the ALT indicates liver inflammation. People in this phase of HBV often have the most seriously progressive disease. <br /><br />In making a diagnosis of HBV and working out which phase a person is in, 3 types of tests are used: serological tests, liver function tests (especially ALT for inflammation), and viral DNA measurement (in Australia until recently only specialists could order this expensive test). <br /><br />There are five commonly used serological tests for HBV. The surface antigen (HBsAg) indicates current Hepatitis B infection. It says "you have hep B now". It is found in serum during the incubation period before symptoms, and persists unless antibodies develop to the surface antigen (anti-HBs). Persistence of HBsAg defines chronic HBV and presence of anti-HBs indicates immunity to HBV infection (either by clearance of surface antigen, or by vaccination). Anti-HBs says "you don't have hep B and you can't get it anymore". * Sometimes anti-HBs wanes to undetectable levels in a person who has immunity to HBV, but there is still immune memory and anti-HBs rises to any immune challenge. <br /><br />(* but see exceptions below)<br /><br />The HBV core antibody (anti-HBc) develops early after HBV exposure and generally persists for ever: it just indicates previous exposure, and doesn't imply immunity (in this way it resembles HCV antibody). It says "HBV was here - and may still be here".<br /><br />There are also tests for the HBV "e" antigen and its antibody (HBeAg and anti-HBe). HBeAg is a marker of viral replication and infectivity, and means there are high levels of HBV DNA in the blood. The person with HBeAg is either in the "immune tolerant" or the "immunoactive" phase of HBV. Loss of the HBeAg with appearance of anti-HBe generally indicates that the HBV DNA levels have been suppressed, the so-called "immune control phase" of hepatitis B - in this case the liver function tests will usually be normal. <br /><br />However absence of HBeAg and presence of anti-HBe also occurs when a person moves into the "immune escape phase", where HBV-DNA levels and the ALT rise again.<br /><br />Putting these tests together, HBsAg with HBeAg means chronic HBV with high infectivity. HBsAg with anti-HBe generally means low infectivity, undetectable DNA and "immune control" but can point to "immune escape phase", with high HBV-DNA levels and liver inflammation.<br /><br />HBV is an oncogenic virus, and unlike HCV, can cause hepatocellular carcinoma (HCC) in the absence of cirrhosis. Of all people with chronic HBV, about 30% will go on to cirrhosis, and 5-10% will go on to HCC. Of people with HBV cirrhosis, about 1 in 4 will go on to liver failure within 5 years. <br /><br />Numerous factors negatively influence HBV natural history and prognosis: host factors (male gender, older age, obesity and diabetes); viral factors (high viral load, genotype C); coinfection (HIV, HCV, hepatitis D); tobacco smoking and alcohol use. Mortality from liver failure or HCC is much higher when there is HIV coinfection. <br /><br />Primary prevention for HBV depends on screening and vaccination of high risk individuals and universal vaccination of infants. People who may have poor immune response (HIV/haemodialysis patients) or who may be at higher risk (people with existing liver disease, health care workers) should have anti-HBs checked after the usual 3-vaccine course, and may need a booster. People, including infants, who have accelerated HBV vaccination schedules should also have a booster at 12 months. Immunocompetent people generally do not need boosters even if anti-HBs wanes. However, 5-10% of people fail to respond to vaccination, and these people should be advised that they may need passive vaccination with HBV immunoglobulin (HBIG) within 72 hours if they are exposed to HBV. <br /><br />HBIG should be given to babies of HBsAg mothers within 12 hrs of delivery, and standard vaccination carried out. <br /><br />The second part of this summmary will present treatment issues and case studies:<br /><br /><a href="http://www.redfernclinic.com/concord/2008/07/other-hepatitis-update-on-hepatitis-b_31.php4">http://www.redfernclinic.com/concord/2008/07/other-hepatitis-update-on-hepatitis-b_31.php4</a>Unknownnoreply@blogger.comtag:blogger.com,1999:blog-2135134153424193830.post-44950478438559466522008-07-31T00:01:00.000+10:002010-01-12T01:01:53.091+11:00"The Other Hepatitis" - An Update on Hepatitis B [PART II]Concord Dependency Seminar Tuesday 23 July 2008 "The Other Hepatitis" - An Update on Hepatitis B. Dr Gail Matthews, St Vincents Hospital Darlinghurst <br /><br />Summary Part 2. Treatment issues and case studies. <br /><br />Dr Matthews pointed out that HBV is a fluctuating disease, and that for the majority, chronic HBV is never "cured". One might wish for HBsAg seroconversion as a goal of treatment, but this currently impracticable. For this reason it is best to think of and manage HBV as a chronic viral illness like HIV, rather than merely a viral hepatitis.<br /><br />(Note: the majority of adults after acute infection, and a small percentage of people each year after chronic infection, may spontaneously clear HBV by developing anti-HBs. Usually this amounts to spontaneous "cure", however even then HBV can return in situations of immunocompromise eg HIV infection, chemotherapy). <br /><br />Overall, about 60% of people with HBV can be managed by regular monitoring and attention to risk factors for disease progression, while 40% need antiviral treatment. However, people can move from one group to the other. <br /><br />The goals of therapy can be defined in several ways, but the essential aim is virological suppression to allow histological improvement, and prevention of HCC and end stage liver disease. <br /> <br />For HBeAg positive individuals, a desirable end-point is anti-HBe seroconversion, with loss of HBeAg. For HBeAg negative individuals, suppression of viral DNA is the essential aim. For all individuals, normalisation of ALT is a good indicator of reduced hepatic injury. <br /><br />Current therapeutic agents are divided into two types, immune modulators (alpha interferon) and antiviral agents (nucleoside analogues NAs). The development of pegylated interferons and a wider range of NAs has improved therapeutic options and outcomes. <br /><br />The two main therapeutic questions are: whether to use an immune modulator vs an antiviral; and whether to use one or two agents (immune modulator plus NA, or two NAs). <br /><br />The benefits of interferon alpha monotherapy for HBeAg positive patients are clear, with reduced rates of cirrhosis and HCC, and increased survival. The treatment aim is to "push" these people into the "immune tolerant" phase of HBV. The advantages of interferon are the finite duration of treatment, durable treatment response (when it occurs), the high rate of HBeAg loss (around 30%), and loss of HBsAg in 3%-8%. Drug resistance does not develop. Disadvantages include unpleasant side effects, high cost, and lower responses with some genotypes and where there is high-level viraemia. <br /> <br />Combination therapy with lamivudine plus interferon alpha for HBeAg positive patients gave higher end of treatment viral response but no higher rates of viral response, eAg seroconversion or sAg seroconversion, compared with interferon alone (Lau et al NEJM 2005).<br /><br />Nucleoside analogues for HBV include lamivudine, adefovir, entecavir, telbivudine, tenofovir and emtricitabine (the first 4 are currently licensed for HBV). The archetypal NA, lamivudine, effectively suppresses viral replication, with reduced liver inflammation and improved liver histology. In up to 50% of HBeAg positive people, it also produces seroconversion to anti-HBe ("pushing" into the immune control phase) however this may take as long as 5 years. For people who do not achieve eAg seroconversion (ie do not develop anti-HBe) the therapy must be continued indefinitely, as it must also for people who are eAg negative (in the "immune escape" phase). <br /><br />Unfortunately, viral resistance to lamivudine develops almost universally with time, especially where there is HIV coinfection. In this situation, alternatives are adefovir, and entecavir; the latter is a more potent suppressor of viral replication, and resistance appears to be less of a problem. It may increasingly be first line therapy for many people. <br /><br />Nucleosides analogues have the advantages of oral delivery with minimal side effects. Treatment is less expensive than interferon, but not when given long-term. There is potential for multidrug resistant organisms, especially when NAs are used sequentially. <br /><br />Management of chronic HBV depends on a thorough assessment including liver function, serological markers, HBV DNA, sometimes liver biopsy (or fibroscan), and cofactors for disease progression (HCV/HDV/HIV). People should be vaccinated for HAV, given clear advice on transmission, and problems of alcohol, tobacco, obesity and diabetes dealt with if possible. <br /><br />Specific treatment is recommended for:<br />• HBeAg positive people who have elevated ALT, and HBV DNA > 20,000 IU/ml<br />• HBeAg negative people who have abnormal ALT, HBV DNA > 2,000 IU/ml, and necroinflammation/fibrosis on biopsy<br />• Cirrhotic patients with any level of measurable HBV DNA<br /><br />Initial Treatment Strategies <br /><br />Immune modulators may be preferred for healthy people < 60 years, with no cirrhosis, a baseline HBV-DNA > 1010 copies/mL, and ALT > 2-3 times normal, and who have genotype A or B (the more responsive genotypes) <br /> <br />Nucleoside analogs can be used for any age adult, for any genotype, with or without comorbidity (including cirrhosis with or without decompensation), a baseline HBV-DNA 109 copies/mL and ALT > 5 times normal. <br /><br />In people with advanced HBV it is important to manage the viral infection aggressively and refer early for transplant assessment. Any patient with cirrhosis should have 6-monthly screening for HCC, using alphafetoprotein (AFP) and abdominal ultrasound (in cases of doubt triple phase CT/MRI). The following groups should also be targeted for HCC screening, regardless of their stage of liver disease: Asian men over 40 years of age; Asian women over 50 years of age; Africans over 20 years of age; and people with a family history of HCC.<br /><br /><br />Case studies (with apologies to Hanna Barbera)<br /><br />Barnie is 36. He has a 12 year history of heroin injecting, previous buprenorphine maintenance on several occasions usually of short duration and with subsequent relapse His current BMT episode is 5 months, dose 8mg/day and he keeps using heroin. <br /><br />He says "I've had hep B and hep C for years." He sometimes shares fits because 'What's the point? I've got both already." He drinks alcohol most days, 30-120g.<br /><br />He is HCV seropositive and HCV-RNApcr positive; HIV negative and HBsAg positive. His ALT is 72, AST 60, GGT and other liver function tests are normal. After strong advice, he ceases sharing injecting paraphernalia, but he continues drinking most days.<br /><br />On subsequent testing his ALT remains elevated. His second HCV-RNA pcr test is negative. He remains HBsAg positive, HBeAg positive and Anti-HBe negative. How should he be managed?<br /><br />Comments: if his HCV-RNA remains negative, he may have ceased reinfecting himself with HCV and cleared the virus. He has "immunoactive" HBV with alcohol as a risk factor. Progressive liver fibrosis can occur in the "immunoactive" phase, and alcohol and periods of HCV infection may have contributed to this. Liver biopsy staging may be helpful here. If he does not have cirrhosis already, could have interferon treatment to try to push him into the "immune control" phase of HBV. He should be strongly encouraged and supported to stop alcohol entirely, and this would be a condition for interferon treatment. An alternative would be long term NA treatment. <br /><br /><br />Fred is 37 and has been on MMT for 6 years. He has not injected drugs for 5 years, and has practically given up alcohol, which he used to drink regularly 30-80g/day. He smokes 40 roll-your-own cigarettes a day.<br /><br />He is HCV and HIV seronegative but has HBsAg, with both e antibody and antigen. He thinks he got HBV from injecting, but doesn't know when. His ALT and AST are usually normal or mildly elevated (<80) and other liver tests are normal. <br /><br />During ketoconazole treatment for toenail tinea his transaminases rose to over 500, with other LFTs normal. He stopped the ketoconazole but his transaminases remained elevated (about twice normal) over the next 2 years. He remained positive for HBsAg, and anti-HBe, and became negative for HBeAg.<br /><br />Fred is against "western" treatment for his liver, and gets herbal treatments from a homeopath in Victoria who runs a telephone consultancy. The cost of these medications ranges up to $60/month plus $60 for each phone consultation. Fred pays the phone bill.<br /><br />Comments: when he had both Anti-HBe and HBeAg, he was apparently seroconverting for e antigen, thus follow up showed loss of HBeAg. As his transaminases remained elevated, HBV-RNA testing was subsequently done, showing <2,000 IU and confirming "immune escape" phase. He therefore needs long term nucleoside analog treatment. There is no evidence for the benefit of homeopathic treatment, and this should not distract him from the antiviral treatment which he needs to prevent severe liver damage. His smoking is a risk factor for HBV disease progression. <br /><br /><br />Pebbles is a 32 year old transsexual who is on BMT for heroin addiction. She has always smoked her heroin and never injected drugs. She was born in Asia: her blood tests show anti-HBc and HBsAg but her liver tests are always normal. She says all her family back home have Hep B. She has anti-HBe and does not have the HBeAg. She asks "I am going to get liver cancer?"<br /><br />Comments: she was probably infected early in life, and is now in the "immune control" phase of HBV. She is at risk of hepatoma even if she remains in the "immune control" phase, and should be screened every six months after the age of 40, or from now if there is a family history of liver cancer. Although it is unlikely she has cirrhosis on this evidence, it is possible. If liver biopsy or fibroscan showed evidence of cirrhosis she should have hepatoma surveillance. <br /><br /><br />Dino is 38 and is on MMT. He has cleared HCV, is HIV negative and had a full course of HBV vaccination 6 years ago. After a recent test showing negative for anti-HBc, anti-HBs and HBsAg, he had two more HBV shots, but remained anti-HBs negative 6 months later. He asks “What's the point of me having all these tests & these expensive shots if they don't work?"<br /><br />Comments: 5-10% of people fail to respond to vaccination, and these people should be advised that they may need passive vaccination with HBIG within 72 hours if they are exposed to HBV. HAV vaccination should be offered if he is not immune. <br /><br /><br />Betty is a 54 year old injecting drug user on MMT with regular alcohol use (40-60g/day most days). She is HCV and HIV seronegative. Her HBV serology is: anti-HBc positive, anti-HBs negative, HBsAg negative, eAg and anti-HBe also negative. Her ALT and AST are always high, with ALT>AST. Should she have HBV-DNA testing? <br /><br />Comments: with isolated core antibody, it is most likely she has waned surface antibody, and a challenge with a vaccine may demonstrate this with anti-HBs becoming measurable. It is also possible she has chronic HBV and low level HBV-DNA despite not having measurable surface antigen. However, it is unlikely that such low levels of DNA would cause clinically significant disease. HBV-DNA testing is probably not needed but she should be advised to reduce her alcohol to safe levels and liver tests followed up 6-monthly.Unknownnoreply@blogger.comtag:blogger.com,1999:blog-2135134153424193830.post-82319936028342305262008-07-22T19:09:00.000+10:002009-03-08T00:55:59.226+11:00Adult ADHD & Substance Use Disorders – Dr Julian TrollorConcord Dependency Seminar Tuesday 22nd July 2008<br /><br />Adult ADHD & Substance Use Disorders – Dr Julian Trollor<br /><br />Dr Julian Trollor is Senior Staff Specialist Neuropsychiatrist at the Neuropsychiatric Institute, Prince of Wales Hospital and Senior Research Fellow of the Brain Ageing Program at the University of New South Wales. He established a clinic for the assessment of adults with possible ADHD in 1995. This clinic now operates as a tertiary service, providing second opinions in difficult cases.<br /><br /><br />Dr Trollor began his presentation by recounting his own experience of filling out a pop-up box which once appeared unbidden on his computer screen. Dr Trollor (who does not have ADHD) was informed...."the responses you have provided indicate that your symptoms may be consistent with Adult ADD. It may be beneficial for you to talk with your healthcare professional about an evaluation.” The pop-up was sponsored by a manufacturer of a pharmaceutical for ADHD.<br /><br />Dr Trollor pointed to the growing popular awareness of Adult ADHD (A-ADHD), with ‘self diagnosis’ being common, shared controversy with its childhood counterpart, and community fears about treatment with a potential "drug of abuse".<br /><br />ADHD is a "neurodevelopmental disorder of childhood onset characterised by impairments in cognitive function (inattentiveness), excessive motor behaviour (hyperactivity) and impaired behavioural regulation (impulsivity).” It is common, with high co-morbidity, and it is often overlooked, despite being relatively easily treated, with treatment improving outcomes.<br /><br />Evidence for the validity of the entity A-ADHD has increased greatly in the last decade and is found in cross sectional, longitudinal and epidemiological studies, family & genetic studies, and neuro-psychological, -physiological, -endocrine and -anatomical studies.<br /><br />Despite progress in understanding of A-ADHD, clinical diagnosis remains problematic: there is no single criterion marker; the core symptoms are dimensional (or spectrum) rather than categorical; co-morbidity can confound diagnosis; the requirement for retrospective childhood diagnosis may create difficulties; the key descriptors are ubiquitous; and the requirement for “significant impairment” is arbitrary. Diagnostic tests are often used but they lack specificity.<br /><br />The DSM IV CRITERIA are listed in the appendix (see Redfern Clinic website). Briefly, the person must have (for the primarily inattentive type) six or more inattention symptoms as well as (for the combined type) six or more hyperactivity/impulsivity items for at least 6 months to a degree that is maladaptive. Some symptoms must be present before 7 years of age, impairment must be present in at least two settings, and symptoms do not occur exclusively during the course of a pervasive developmental disorder, psychotic disorder and (as always in DSM-IV) are not better accounted for by another mental disorder.<br /><br />Symptoms can be grouped in four types:<br /><br />1. attentional, with difficulty sustaining attention (during lectures, reading, in conversation, at work), easily distractability (eg by extraneous sounds, activity), day-dreaming, making careless mistakes - the primarily inattentional type is more common among women.<br />2. organisational, often losing things, forgetting day to day activities or appointments, having difficulty organising tasks, following verbal instructions - these may be more pronounced in unstructured settings, and therefore may become more problematic in adults, upon leaving a structured setting like school/college.<br />3. hyperactivity, being always “on the go” physically, being fidgety or restless, having difficulty relaxing, having racing thoughts or many ideas, taking on multiple tasks at once without finishing many.<br />4. impulsivity, talking excessively, making tactless comments, interrupting conversations, difficulty waiting turn, taking risks (eg driving, thrill seeking, financial risks), explosive temper, irritated easily by minor frustrations, quick mood changes.<br /><br />Hyperactivity may be less marked in adults in whom the hyperactivity may be more a phenomenon of mental cluttering, akin to a sense of continuous "noise" - quite distinct from anxiety. A meta-analysis of follow-up studies of children with ADHD showed an age-dependent decline in ADHD symptoms: 65% experienced partial remission in adulthood, with full ADHD diagnosis persisting in approximately 15%. The severity of ADHD symptoms in childhood appears to predict persistence into adulthood.<br /><br />A large cross-national survey estimated adult ADHD prevalence across ten countries to be 3.4% (range 1.2-7.3%); one US study estimated current prevalence of adult ADHD at 4.4%. As Dr Trollor pointed out, these estimates suggest that A-ADHD is one of the more common mental disorders.<br /><br />ADHD is a condition with a high genetic loading - family studies suggest 80% of ADHD symptoms can be attributed to genetic factors - with genetic-environmental interactions also playing a role, especially disrupted attachment, early abuse, and chaotic environment. The candidate genes are those involved in motor activity and attentional processes, and include DAT gene (SLC6A3), COMT (Catechol-O-methyltransferase), DBH (Dopamine beta-hydroxylase) and dopamine receptors (especially DRD4), however no single gene accounts for more than 5% of the phenotypic variance of ADHD.<br /><br />Adult ADHD has major consequences: adults with ADHD are less likely to be employed full-time and more likely to have unstable work records, have significantly lower household income, have fewer close friends, more difficulty sustaining relationships and higher likelihood of having contracted a sexually transmitted disease. They are more accident prone (more traffic violations, severe accidents, more likely to be ‘at fault’), and have higher medical costs.<br /><br />Diagnosis<br /><br />In making a diagnosis, it is important to consider the motive/catalyst for presentation, whether owing to legal & forensic issues, a transition from a more to a less structured environment, or on cessation of substance use. Some adults come forward for assessment following diagnosis of their children. Self diagnosis is not a reliable indicator of the presence or absence of ADHD<br /><br />The diagnostic pathway is to assess current symptom profile, severity and impact, to establish and corroborate childhood diagnosis (from self-report, parental and school reports, previous psychological or medical assessments) and to evaluate co-morbid (or diagnostically confounding) conditions - people with ADHD have increased risk of a diagnosis of antisocial personality disorder, of anxiety disorders, major depression and substance use disorders.<br /><br />Bearing in mind the partial remission of ADHD in many or even most adults, it is important to consider the actual impact of symptoms on the patient's social, occupational, educational or family life as well as their current coping strategies. Many people cope well with or are untroubled by having features of ADHD and it is not uncommon for people with ADHD to be less likely to complain than their partners or family.<br /><br />Establishing a retrospective childhood diagnosis is often a challenge, especially for people with major psychosocial problems including substance use disorder (SUD) who may have chaotic histories and be estranged from family. Where possible, informant interview can provide corroboration of the nature and extent of both current and past symptoms. Evidence can be gleaned from academic records, number and type of jobs, history of impulsive infringements, self esteem and interpersonal problems (resulting from impulsivity, poor anger control and organisational skills), and patterns of drug use which may suggest self-medication of symptoms. Sometimes there is a suggestive ‘paradoxical response’ to street amphetamine - ie a calming effect rather than stimulation.<br /><br />Further assessment may include the use of rating scales, and require physical examination, bloods testing including thyroid function, urine toxicology, EEG, CT/MRI of the brain (a history of head injury may be common in people ADHD owing to their accident proneness, but brain injury may also sometimes mimic ADHD symptoms), and neuropsychological examination including CPT. Not all of these will be required in every case.<br /><br />Substance Use Disorders and A-ADHD<br /><br />The epidemiological relationship between substance use disorders (SUD) and A-ADHD is bi-directional, with increased rates of SUD in ADHD clinic samples (for alcohol 17-45%, other drugs 9-30%) and of ADHD in SUD clinic samples (around 25%).<br /><br />Relative risk of SUD in follow-up of ADHD cohorts is increased up to five-fold, with earlier and increased use of alcohol, tobacco and other substances in adolescents with ADHD compared to controls, and ADHD in childhood and adolescence a significant predictor for later substance use - the risk is greater if the individual has conduct disorder or mood disorder. The relationship of with childhood ADHD is strongest for tobacco smoking, and it is likely a sub-group of individuals with ADHD self-medicate with tobacco: nicotine has been successfully trialled as an intervention.<br /><br />People who have both SUD and ADHD have poorer outcomes. However, people treated with stimulants in childhood and/or adolescence have an equivalent or lower incidence of SUD compared to those untreated, and the use of stimulant medication to treat people with ADHD does not increase the risk of developing substance use disorder.<br /><br />It is preferable to perform diagnostic assessment during long-term abstinence (whereby opioid substitution treatment with abstinence from other problematic substance use can be considered abstinence) and, as with other co-morbidities, active SUD should be addressed prior to specific ADHD treatment. It should be borne in mind that ADHD medications have no demonstrated efficacy for the treatment of ADHD where there is co-morbid SUD, nor have studies been conducted of use of psychosocial interventions.<br /><br />Dr Trollor recommended (and feedback is welcome about) the Draft Guidelines for the Assessment and Management of Attention Deficit Hyperactivity Disorder (National Health and Medical Research Council and the Royal Australasian College of Physicians) accessible at <a href="http://www.racp.edu.au/">http://www.racp.edu.au/</a> ( follow link under ‘announcements’).<br /><br />From these guidelines, the following are some key recommendations for best practice for assessment and diagnosis of ADHD in adults when co-morbid SUD is present:<br /><br />People with personality disorder and/or substance abuse should be referred for evaluation of ADHD if they present with a significant level of hyperactivity / impulsivity accompanied by inattention.<br />Medication treatment for ADHD co-morbid with substance misuse should only be provided by a medical practitioner with expertise in both conditions.<br />ATX should be the first medication trialled if there is co-morbid substance abuse.<br /><br />Management of A-ADHD<br /><br />Dr Trollor's approach to management is to create a hierarchy for interventions, generally treating pressing co-morbid conditions first, as these may increase the expression of ADHD symptoms, and providing for further observation in cases where the diagnosis is uncertain.<br /><br />Specific A-ADHD treatments include: education (through internet, books, support groups); drug therapies (methylphenidate 0.3-1.0mg/kd/day; dextroamphetamine 0.2-0.5mg/kg/day, desipramine, imipramine 25-100mg; and others including atomoxetine, buproprion, MAOI, lithium, venlafaxine, SSRI, CBZ, clonidine,); cognitive & other behavioural therapies to increase organisational skills, impulse control, and self monitoring.<br /><br />Psychostimulants<br /><br />Against a backdrop of a rapid rise in prescription rates, unease about use of stimulants arises from several considerations. With continuation of treatment from childhood there are potentially decades of exposure to stimulants. Should this be open-ended? What are the risks of psychological dependence, and harmful use/dependence given the high psychosocial and substance comorbidity in adults with ADHD?<br /><br />Stimulants are effective in adults with ADHD although the number of studies is small. Available efficacy data for adults give response rates between 25 and 78 percent for methylphenidate (MPH), in a similar dose range as for children, and a modest literature suggest similar efficacy for dexamphetamine (DEX) - there is no direct evidence to support use of high or very high doses of MPH or DEX.<br /><br />Current evidence suggests the use of stimulant medication to treat people, including children, with ADHD does not increase the risk of developing substance use disorder. However, there is evidence of diversion and misuse of prescription medications for ADHD among school students and college students, with between 16 and 29 percent of students on stimulant medication having been asked to give, sell or trade their medication at some time. While some individuals report using diverted stimulants to self-medicate for ADHD symptoms, others use them to enhance performance, or for their euphorogenic effects.<br /><br />Dr Trollor advises stimulant treatment should be reserved for people with pervasive symptoms causing significant difficulty, and where clear goals can be identified, the patient is motivated to work on broad range of solutions and where adequate follow-up and monitoring is available.<br /><br />Stimulant treatment is relatively contraindicated where ADHD symptoms are present but are not the primary problem, where the clinical diagnosis conflicts with patient ‘self-diagnosis’, where there is severe co-morbid psychosis or mood disorder, or continuing problematic substance use. One warning signal is where the patient has many past prescribers of stimulants.<br /><br />Non-stimulants, long-acting stimulants or anti-depressants are preferred to short acting stimulants, which are strongly reinforcing drugs. Pharmacotherapy should be trialled for effectiveness on an individual basis and carefully monitored for benefits and adverse effects; a contract for stimulant treatment may include regular review (possibly including urine toxicology - a moot point at this seminar) and an ongoing goal of abstinence.<br /><br />Atomoxetine is a predominantly presynaptic noradrenaline transporter inhibitor without euphorigenic and reinforcing properties, with several studies showing benefit in children and adults. There is also a small number of studies for buproprion (an indirect NA & DA agonist), likewise with a low “abuse potential”.<br /><br />Stimulant Dose<br /><br />There are no trials of ‘high’ or ‘very high’ stimulant doses in adults with ADHD, and low dosing appears to be appropriate for most individuals. Dr Trollor recommends cautious titration eg commencing at DEX 0.15mg/kg/day or MPH 0.3mg/kg/day and aiming for DEX < 0.5mg/kg/day or MPH <1.0mg/kg/day. For the stimulant-naive patient, Dr Trollor recommends commencing DEX 5mg mane & midi (or MPH 10mg mane & midi). Smaller doses may also be required if patient on other psychotropics or has comorbid anxiety or sleep disorder. Animal models demonstrate a biphasic response to DEX: low doses (DEX < 1.0mg/kg) reduce, and higher doses DEX 1.0-5.0mg/kg increase, locomotor activity, which may correspond to a “high” in humans. As stimulants lower the seizure threshold in animals, are associated with (transient) emergent ‘tics’ in 10% of stimulant treated children, elevate pulse and blood pressure (low dose stimulants increase BP by an average of 3-5mmHg) low doses and close monitoring are indicated where there is co-morbid tic disorder, hypertension or seizure disorder. Although psycho-stimulants can induce paranoid delusions, auditory & visual hallucinations, this is mainly seen with intravenous use. Inter-individual pharmacokinetic variability (especially for MPH, where peak serum levels vary up to five-fold) provides an argument for a trial of higher doses in some individuals with non response to low doses - monitoring stimulant levels may be helpful, as may a second opinion. One difficulty is how to monitor response, whether subjectively or using self rating scales, observer rating scales, or neuropsychological/neurophysiological testing. Many people will feel better using low dose stimulants, regardless of whether they have ADHD or not.<br /><br />This conundrum was illustrated in a complex case study presented in the second half (see separate posting). Some parting questions: how can such a prevalent condition, especially in children, be conceived of as a disorder? In an evolutionary sense, does ADHD confer an individual or collective biological advantage? In an anthropological sense, does it represent a failure of adaptation to modern life? Summary by Richard Hallinan, based on Dr Trollor's presentation and powerpoint file.<br /><br />Clinic web page: <a href="http://www.redfernclinic.com/#news">http://www.redfernclinic.com/#news</a><br /><br />Concord Seminar blog: <a href="http://concorddependency.blogspot.com/">http://concorddependency.blogspot.com/</a>Unknownnoreply@blogger.comtag:blogger.com,1999:blog-2135134153424193830.post-81572004671037435692008-05-20T19:11:00.001+10:002009-03-31T23:36:23.547+11:00Treating the Addicted Brain: Agonists, Antagonists and Modulators.Concord Dependency Seminar Series. Tues 20th May 2008.<br /><br />Treating the Addicted Brain: Agonists, Antagonists and Modulators.<br /><br />Speaker: Stephen Jurd, Psychiatrist, RNSH and RANZCP director of training.<br /><br />Dear Colleagues,<br /><br />Dr Jurd commenced by almost stating the obvious: the problem of addiction starts with the brain. The origin of the behaviour does not lie in reasoned thoughts, which are late in evolution, but in reward pathways, organised in the hind-brain. From this ancient part of the nervous system, the responses are transferred to the frontal lobes where conscious thoughts, decisions and deductions are made regarding diverse ways to satisfy the more primitive urges. While most reward pathways are related to survival and procreation, drug use mimics such responses chemically, causing satisfaction, pleasure and desire to repeat the experience. The concept of craving was discussed in depth - it is not easy to define and perhaps best to simply call it ‘the motivation to use the drug’.<br /><br />Equally, a definition of clinical or behavioural ‘salience’ is difficult, yet it is crucial to understanding and defining addiction, first clearly done by the redoubtable Griffith Edwards. Dr Jurd suggested one way to define ‘salience’ is to look at the person’s ‘top-40’ items of interest which for non-addicted people would range across a variety of things from food to music to work, family and hobbies. For the compulsive drug user or alcoholic, gambler, etc this would be a very short list, largely related to their drug or behaviour of interest. This is the ‘narrowed repertoire’ of drug use behaviour.<br /><br />We were told of a recent pivotal study by Anne Rose Childress working at Philadelphia with Charles O’Brien’s group. They found significant brain responses on real-time PET scanning from ‘split-second’ projections of drug-related images, despite them not being seen or recognised consciously in a group of 22 long term cocaine users. These were also closely correlated with drug, violence or sexually explicit images shown several days later in relevant cases (and not in controls). So, despite not realizing it at the time, these long-term cocaine users’ brains had registered the brief images unconsciously and committed them to memory. Thus for the first time we have evidence of addiction related cues and/or priming occurring ‘outside awareness’. There was also some corroboration of this remarkable finding from another study involving similar brain responses to cues for ‘‘unseen’’ monetary rewards (Pessiglione). The advertising industry may have known of these matters for years!<br /><br />Decisions in adolescence are agreed to be most important in learning and memory, and some regard drug addiction as an ‘illness of youth’ [cf Stanton Peele ref below]. We were told that there are maximal numbers of synapses in the adolescent brain which then decrease with age. Synaptic structures are highly dynamic, and adult brains are able to make new cells. Both exercise and stroke can lead to increased neural production and brain cells move towards the injury site. All of this is contrary to traditional teaching about the CNS being unable to repair or replace damaged areas.<br /><br />Addiction is not simply withdrawal, but craving, the inclination to use, the very nature of dependence and a whole clinical syndrome which persists, sometimes well after drug/alcohol use has ceased. DSM defines ‘early remission’ as up to 12 months. We were told that addiction is common, has social and medical impacts, as well as numerous psychiatric complications.<br /><br />There must be a system of reward, hard-wired into the mammalian brain where intuitively certain people and/or events are memorable, striking and causing a ‘yearning’. And such a system would just be normal. Dopamine has been identified as the relevant neurotransmitter.<br /><br />However one defines them, ‘cravings’ lead to the conscious motivation to seek and use the drug, with a euphoric recall, and with often pleasant associations. “This feels sooo … good”. This is the case for both stimulatory and sedating drugs. Dopamine from the nucleus accumbens is crucial for reinforcement and reward; attention, memory and learning. These mesolimbic pathways are not unique to opiates but are similar for nicotine, alcohol, benzodiazepines, stimulants, etc.<br /><br />The next result is to trigger ‘yearning’ for the experience to be repeated. Drugs excite the reward pathway and this then leads to addiction. At a certain point the individual becomes aware of the dangers and the illogical nature of their behaviour, yet continues with it. Similarly, they may be able to rationalise with a counsellor, doctor or family member that it is harmful to continue (cortical), yet the behaviour persists (driven by limbic pathways).<br /><br />We were shown a familiar brain diagram from The New England Journal of Medicine: Neural Reward Circuits Important in the Reinforcing Effects of Drugs of Abuse [Cami J, Farre M. 2003 349:975-986].<br /><br />Stimulants may also cause direct stimulation of dopamine production. On the other hand, sedatives inhibit the production of inhibitors of dopamine and so lead to increased dopamine concentrations. Thus in the reward pathway all drugs lead to increased dopamine at critical points in the hind-brain and so lead to increased learning, attention and focus on the drug use.<br /><br />Aversive Agents<br /><br />Disulfiram does not affect the dopamine pathway, but has its action through the frontal lobe using logic and reasoning. With this the person learns that “it is dumb to take alcohol with this”, and so even when cravings are strong the addict may choose not to consume alcohol, knowing the likely consequences.<br /><br />Agonists/Replacements<br /><br />Most of these provide a longer acting form of the drug which avoids the cycle of intoxication and withdrawal. For example methadone is a long half life drug, decreasing heroin use and improving quality of life. The person learns that they simply do not need to use additional opiates as there is little gain.<br /><br />Nicotine is the same drug, with a safer delivery of drug via patches, gums and inhalers. Post-myocardial infarct patients do better on patches.<br /><br />Dexamphetamine - there is no pharmacological basis to change to this from methamphetamine as the half-life of ‘dex’ is 10-12 hours compared to 9-15 hours for methamphetamine. A longer acting form may be more appropriate for addiction treatment.<br /><br />Benzodiazepines – theoretically for alcohol but they are not satisfactory, both are disinhibitory agents, acting on GABA receptors.<br /><br />Partial agonists<br /><br />Buprenorphine (for opiate dependence).<br />Varenicline (a nicotine receptor blocker).<br /><br />Antagonists<br /><br />Naltrexone – a long acting opioid antagonist, works when taken but does not chemically modulate cravings for opioids (might do so psychologically according to Brewer). For alcohol with time it can modulate cravings but unlike disulfiram the person will not become ill if alcohol is consumed.<br /><br />Rimonaband – cannabinoid antagonist - not yet available in Australia – used overseas for obesity(?).<br /><br />Odansetron (Zofran) – serotonin-3 antagonist with promise for alcohol abuse in very low dose [see RCT Bankole Johnson link below].<br /><br />Modulators<br /><br />These take time to work, and act less on receptors but modulate other areas which then lead to change in receptors and/or their neurotransmitters.<br /><br />Acamprosate modulates the balance of GABA. We were reminded that this drug is really only of benefit for those wishing to cease alcohol use completely whereas those on naltrexone are more likely to be able to manage controlled drinking better (although this is not approved under PBS prescribing criteria). In a similar way in depressives, SSRI drugs also take time to have their clinical effects, rather than a chemical effect on receptors which theoretically occurs straight away.<br /><br />We were then brought back to the traditional in-patient treatment of alcoholism and drug addiction, something which is now rare as authorities have closed down many detox and rehab wards. The justification has often been that they were “not cost-effective”. Dr Jurd quoted the highly reputed “Project Match” which found double the rate of abstinence at one year in those who received an in-patient stay as part of their treatment when compared with those who only received out-patient services. Note that entrants were not randomised so the significance is limited to an non-causal association.<br /><br /><br />Two case histories were then presented and ‘work-shopped’ in some detail:<br /><br />Case 1: A youth with excess alcohol use causing serious health, legal, and social problems.<br /><br />Case 2: A middle-aged set-in-his-ways professional with smoking and alcohol excess with hypertension. He stopped nicotine after 12 months but unable to decrease his alcohol.<br /><br /><br />Summary written by Judith Meldrum and Andrew Byrne. Further details of the case histories and workshop discussion will be sent as a supplement later when time allows. See our summary of “The neurobiology of addictive behaviours” on web page: <a href="http://www.redfernclinic.com/c/2005/12/alcohol-pharmacotherapy-macquarie.php4">http://www.redfernclinic.com/c/2005/12/alcohol-pharmacotherapy-macquarie.php4</a> Web site: <a href="http://www.redfernclinic.com/concord/">http://www.redfernclinic.com/concord/</a><br /><br /><br />References: Childress AR, Ehrman RN, Wang Z, Li Y, Sciortino N,,, O’Brien CP. (2008) Prelude to Passion: Limbic Activation by "Unseen" Drug and Sexual Cues. PLoS ONE 3(1): e1506<br /><a title="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0001506#pone.0001506-Pessiglione1" href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0001506#pone.0001506-Pessiglione1">http://www.plosone.org/article/info:doi/10.1371/journal.pone.0001506#pone.0001506-Pessiglione1</a><br /><br />Johnson BA, Roache JD et al. Ondansetron for Reduction of Drinking Among Biologically Predisposed Alcoholic Patients. A Randomized Controlled Trial. JAMA (2000) 284:963-97<br /><br />Peele S. The Surprising Truth About Addiction. Psychology Today (2004) May-June: 43-46 <a href="http://www.peele.net/lib/surprising.html">http://www.peele.net/lib/surprising.html</a><br /><br />Pessiglione M, Schmidt L, Draganski B, Kalisch R, Lau H, et al. (2007) How the brain translates money into force: a neuroimaging study of subliminal motivation. Science 316: 904–906 <a href="http://www.sciencemag.org/cgi/content/abstract/316/5826/904">http://www.sciencemag.org/cgi/content/abstract/316/5826/904</a><br /><br /><br /><br /><br /><br /><br /><br />Case 1: A youth with excess alcohol use causing health, legal, and social problems.<br /><br />• Your 18 yo patient Mark faces serious charges related to two events of driving under the influence of alcohol since his 18th birthday - the second was high range BAL, the accident with near fatal consequences but only mild injury (a broken clavicle).<br />• He has a number (3 or 4) of prior arrests for alcohol-related offenses (drunk and disorderly) during 2007, however these were handled by the police with warnings, no fines and no convictions recorded.<br />• He was treated at St Vincents ED for severe lacerations to his chest and abdomen from diving while intoxicated into water at Darling Harbour earlier this year.<br />• Blood tests from hospital after his recent car accident are consistent with alcoholic hepatitis (AST 74, ALT 40, GGT 104).<br />• Mark gives a history of drinking alcohol regularly from age 15, and only occasionally before that. In his last year of school (Year 10, 2006) he drank nearly every weekend at parties, typically as much as 12 schooners of beer (180g or18 standard drinks).<br />• Although at that stage his drinking was not daily, he would often have 2-3 schooners of beer/day on the verandah after school, and would hide the bottles as his parents did not approve. Alcohol was freely available in the family home.<br />• He left school in year 10 and worked as a plumbers’ apprentice, but couldn’t cope and now does concreting<br />• His social life has been based on alcohol since age 15, all his friends drink.<br />• By age 17 he was drinking after work typically 2-5 schooners (30-75g), and going into town nearly every weekend, where he admits he would drink until he was "blind" - he would lose count of how much he drank, and found it increasingly difficult to get drunk.<br />• In 2008, with daily drinking part of the work culture, he was regularly getting heavily drunk.<br />• he used to play a lot of football, now he couldn't be bothered. Alcohol took priority - "I chose the grog over my girlfriends"<br />• since early 2007, he admits to feelings of loss of control, that he would like to be able to stop, feeling bad about needing beer to socialise (eg needing to take beers from the fridge with him when going out with mates).<br />• There is no history of injecting drug use, and he does not use cannabis or amphetamines.<br />• From primary school he was noted to be inattentive and hyperactive in class, and it was suggested he be assessed for possible treatment for attention deficit hyperactivity disorder (ADHD). His parents decided against such treatment.<br />• There is no history suggesting conduct disorder as a child and no evidence of antisocial behaviours as an adult, other than under the influence of alcohol.<br />• There is a strong family history of problematic alcohol use including three grandparents, one maternal uncle and Mark's own father, who has however now apparently returned to controlled drinking.<br />• Mark has been warned by solicitor that he has a high risk of a gaol sentence.<br />• What treatment is appropriate?<br /><br />• Counselling?<br />• Groups?<br />• Acamprosate<br />• Naltrexone<br />• Disulfiram<br />• Dexamphetamine?<br />• SSRIs<br /><br /><br />Case 2: A set-in-his-ways 45 year old journalist with smoking and alcohol excess with hypertension. He stopped nicotine after 12 months but unable to decrease his alcohol.<br /><br />• Your patient Robert is a 44 year old journalist who is worried alcohol and cigarettes are going to kill him.<br />• first alcohol was “shandy' as kid occasionally, then regular age 18, never alone at that stage, daily from age 21, still not alone, still sociable.<br />• Binging was frequent in his 20s, after he finished work at 2.30pm, he went across to the “journos” or to the pub and drank with till he dropped.<br />• Later his style was pub drinking alone for 2 yrs,<br />• He has been drinking alone at home for the last 8yrs.<br />• He was arrested for DUI after a MVA age 25, also charged once with drunken resist arrest.<br />• He has had no recent alcohol related work or legal problems. He never drinks and drives anymore.<br />• He is still –and contentedly - single and now works evening shifts till midnight, buys a six pack of beer and drinks it all from 12mn to 3am to get to sleep.<br />• If he bought a case of beer, he is sure he would lose control.<br />• He sometimes goes to footie on a Sat, tends still to stop at 6 beers. If he eats first, tends to stop.<br />• He almost never drinks anything other than beer nowadays<br />• He is quite happy with life, not interested in getting a social life, and really only concerned with his health, and not having a heart attack or stroke<br />• He holds down his job without difficulty<br />• Robert tried zolpidem for sleep when he tried alcohol abstinence for a week last year, short action was the main problem. He doesn’t think he has ever had alcohol withdrawal, but he hasn’t actually had a day off alcohol in many years except with zolpidem.<br />• Cannabis experimented only, nil current. Nil IDU<br />• Cigs 30-35 BH special filter; smoking since 17; 35 pack-years. Stopped smoking for 12/12 seven years ago, added 12 kg in weight. He tried NRT and failed.<br />• His father was a heavy drinker in his heyday, but less now; also HIS father. Mother is a non-drinker. Of 2 sisters, one is a “social drinker”, other is teetotaller.<br />• Robert has no other illnesses or symptoms on “systems review”.<br />• OE: BMI 30.5; BP 160/95, pulse 78 regular<br />• obese, smooth hepatomegaly, normal testicles and no g'mastia, koilonych, couple spider naevi only.<br />• Non-tender abdo and heart normal to palpation and auscultation.<br />• Height 169 cm, spirometry. 2.8/4.0 = 70%. (Pred VC 4.4 L, SD 0.5)<br />• Bloods tests are all satisfactory other than lowish testosterone (9.8 on a 3pm collection) and cholesterol borderline (was normal two years ago). LFTs normal<br />• Roberts is worried about his drinking and smoking, asks what he should do.<br />• He doesn’t think he could tackle cigarettes and alcohol at the same time<br />• He insists he really doesn’t want to stop drinking altogether, and hopes for “controlled drinking”.<br />• What are the priorities?<br />• Are medications appropriate for Robert?<br />• What should you write back to his GP?<br />• Robert’s blood pressure was stabilised on telmisartan and he set himself a goal of 3 schooners of beer/day and 2 alcohol free days per week. He agreed to try nictoine patches, two /day if needed.<br />• He canceled his follow up appointment.<br />• A year later he has returned, now 4 weeks off cigarettes using varenicline and seeks advice about his drinking which has not changed. He is still adamant that he wants to cut back rather than stop.<br />• He has major dental; work coming up in a fortnight.Unknownnoreply@blogger.comtag:blogger.com,1999:blog-2135134153424193830.post-57155596386909097402008-03-19T01:20:00.001+11:002009-03-31T23:37:30.119+11:00Subject: “Practising in Addiction Medicine: how not to be sued!”Subject: “Practising in Addiction Medicine: how not to be sued!”<br /><br />Speaker: Professor Robert Batey.<br /><br />Concord Seminar Tuesday 18th March 2008 7pm.<br /><br />Held at Concord Hospital (Western Sydney, Australia), Conference Room No 1.<br /><br />Professor Batey began by asking his audience to consider why this subject was being covered and also why he had been asked to speak on it. He pointed out that despite doctors being of a certain age and seniority, mistakes and miscalculations could still occur. A prevention strategy was essential using established safeguards. However, when these failed, such errors need to be dealt with appropriately and openly. This applies to doctors, nurses and all allied health professionals.<br />No amount of renown could avoid this issue. No connection with great physicians, great institutions or fine academic reputation could help when things go wrong. We were told that despite a love of the profession and hitherto keeping out of the way of lawyers, none of us should become complacent or over-confident that it would remain that way.<br /><br />Connections with great physicians could help in one respect: by following their examples in what they taught about good medical practice.<br />The art and practice of medicine.<br />The value of spending time with patients.<br />The need to be ‘vulnerable’ rather than ‘all-knowing’.<br />The absolute necessity to know what you are doing while admitting any areas of uncertainty.<br />The reality that you might appear to be rude while still acting consistently and fairly.<br />Patients may accept mistakes if you demonstrate that your are sincere and competent.<br /><br />We can all name some great physicians we have worked with but it would be hard to match Dr Batey’s list of mentors: Allan McGuiness, Charles Ruthven Blackburn, Sheila Sherlock, Mr Michael Stephens, Dr Dick Richards. Those who worked at Sydney’s Prince Alfred Hospital or Sydney University may know three of these.<br /><br />Some behaviours which patients and colleagues may sometimes overlook include:<br />Aloofness.<br />Use of long phrases no one can understand.<br />Gruffness to the point of rudeness.<br />Late for rounds but never missing them.<br />However, this is contingent on the clinician displaying consistent excellence and reliability in the longer term, leading to the earning of respect.<br /><br />In the field of Addiction Medicine there is another credential needed: A capacity to set boundaries. At this we were shown a slide of the Great Wall of China!<br />In order to demonstrate some ways NOT to practise we were shown some cases from 2007:<br /><br />Mr TM<br />Presents with female partner<br />Both on methadone: 65mg and 50 mg respectively for >10 yrs<br />Receiving 4 take away doses.<br />Neither are employed at present but both had been working in local area 12 months ago.<br />No children at home<br /><br />SO far so good but<br />They want to switch to oral Physeptone (methadone tablets) so they can just pick up scripts for 2 weeks supply.<br />They also admit to not sleeping well and to using benzodiazepines regularly.<br />No other major issues.<br /><br />Main issue is a desire for increased “freedom”<br />Totally anti-buprenorphine as partner had tried to change and failed miserably<br />They talk constantly and when one stops to draw breath the other starts up<br />They have no insight into the issues<br />It is late in the day<br /><br />You weaken and write their first script of physeptone tablets, enough for 5 days “to see how they go”.<br /><br />No no no!<br />This is dangerous<br />It is unwarranted<br />It is indefensible<br />At this point……<br />Is there a way forward??<br /><br />Mr JF:<br />40 yr old, unemployed hairdresser<br />Past heavy alcohol intake (120 gm/d as beer) Now nil<br />Lives alone, no contact with children<br />Had one admission for pancreatitis 8 yrs ago. Apparently this settled.<br />Now complains of abdominal pain on a daily basis<br /><br />Taking:<br />Oxycontin 10 mg qid<br />Oxycontin 20 mg tds<br />Oxycontin 40 mg prn<br />Asks for proladone suppository twice a day to add to his pain relief program<br /><br />You give him proladone<br /><br />You have no idea what his pain is due to or indeed if he has pain at all.<br />He is dependent, he has a “dog’s breakfast” of a management plan.<br />BUT HE LOVES YOU for being so ‘caring’ !!!<br /><br />The state pharmaceutical authorities may not be sympathetic - although after removal of the 2 month rule on opioid prescription in New South Wales in 2006 this may be ‘legal‘ even though it may be ‘poor medicine’.<br /><br />Ms GG, aged 38.<br /><br />Admitted to local hospital semi-conscious with signs of pneumonia.<br />Uncertain what is happening but assessment reveals:<br />Pneumonia of right lower lobe.<br />Obtunded with pin point pupils.<br />Injection marks L ante cubital fossa.<br />Poor nutrition.<br /><br />Lives with husband and 3 children 10, 9 and 4.<br />She does not work, he is a motor mechanic.<br />No major past medical problems.<br /><br />Both she and he are on methadone program.<br />She is on 80 mg/d and he 90 mg/d.<br />Both get 6 takeaway doses per week.<br />No safe storage sites at home<br />No urine drug screens performed in past year.<br />Pharmacist concerned regarding stability.<br />Why does she get 6 T/A’s….. “Well, my husband gets them”.<br />She responds to Narcan injection subcutaneously.<br />Admits to injecting her doses.<br /><br />Assessed for HCV and HBV and has both.<br />1 Child has evidence of exposure to HBV.<br />Vaccination program not completed.<br />Is this all OK?? Should there be a full review of their dependency treatment?<br />Mr BJ had Crohn’s disease for 15 yrs.<br />Several recurrences when Inflammatory Bowel Disease (IBD) treatment reduced.<br />Surgery x 3, fistula complicating this.<br />Intermittent analgesia when in hospital.<br />Tried heroin from friend “for pain relief”.<br />Now on methadone program 50mg/d.<br />Presents wanting pain relief from IBD.<br />He convinces you of his pain.<br />He asks for morphine injections prn.<br />You are convinced of his need for pain relief.<br />You write script for morphine ampoules and arrange for him to come in for doses when needed.<br />He is found dead with signs of O/D. Not a good situation.<br /><br />Ms HT is a 78 year old widow<br />Dependent on benzodiazepines you commenced years ago for insomnia.<br />You become convinced benzos are bad for people and discuss trying to withdraw them which she refuses.<br /><br />Admitted to hospital for an acute surgical problem<br />She experiences a significant withdrawal as no-one took a medication history. She decides that she was not adequately informed about the risks and sets a litigation process in motion.<br />Who should have done more?<br /><br />The next topic was “WHAT AM I DRIVING AT” which reminded us that it is OUR RESPONSIBILITY to ensure that patients are safe to drive, operate machinery and look after children while taking medication. All patients should be warned that new medication and changes in doses of existing drugs, including alcohol, may affect ability to perform adequately.<br /><br /><br />Professor Batey’s final advice to us was:<br />Spend time taking a good history and performing a full physical examination.<br />Communicate appropriately with your patients.<br />Document findings and management plans in the notes.<br />Evaluate progress rationally and regularly.<br />Do not become enmeshed with patient stories rather than reality.<br />Set boundaries clearly and compassionately.<br />Seek peer support.<br />Adhere to good clinical practice guidelines.<br />Seek second opinions in unusual circumstances where guidelines may not apply.Unknownnoreply@blogger.comtag:blogger.com,1999:blog-2135134153424193830.post-44773541273750785262008-02-06T02:39:00.000+11:002008-11-27T03:23:04.468+11:00Comparisons from UK, Victoria and NSW.Comparisons from UK, Victoria and NSW. Drug dilution, crushing, take-aways: the practice versus the evidence. February 05, 2008<br /><br />Presenter: Dr Nicholas Lintzeris.<br /><br />Dear Colleagues,<br />Dr Lintzeris began by describing his shock at the state of skin and veins in a large proportion of drug users in England when he started a sabbatical session at the National Addiction Centre and Maudsley Hospital in 2003. He showed some unflattering photographs of lower limb ‘war-wounds’ inflicted by hypodermic needles, infections, impure brown heroin and neglect. Most of these people had ‘worked through’ their upper limb then moving to the legs so that 20 to 50% of patients in maintenance treatments were using their groin veins for access.<br /><br />The street heroin used was of the Afghan or ‘brown‘ variety, needing lemon juice or acetic acid to make it soluble. Even then it was still caustic to the veins. Dr Lintzeris noted that there were very high rates of crack cocaine use in English patients, up to 40% smoking it regularly whilst in treatment. He quoted the mental and physical toll this took on the lives of addicts and their families. Alcohol and sedative use was also common. Notably, one common drug of abuse was amitriptyline (‘Tryptanol’, ‘Endep’), an antidepressant not known for recreational use in Australia.<br /><br />Balancing the intravenous damage to some extent (and perhaps because of it) there was a high proportion of drug users who did not inject at all. Up to 40% were smoking, snorting or swallowing their drug of choice at the time of entering treatment. In Australia about 90% of addicts entering treatment are injectors.<br /><br />Dr Linzeris noted two main differences in maintenance therapies. Dose levels were generally in the low range (30-50mg daily) and the medication was usually given as “take away” bottles of weak solution rather than being taken under supervision. The use of 1mg per 1ml solution had parallels with the common practice in Victoria of ‘topping up’ take-away bottles with up to 100ml of water or cordial to discourage injecting.<br /><br />Some graphs were shown of methadone treatment in Victoria from 1985 when there were only about 100 patients in treatment. By 1996 there were nearly 4000, and by 2003 about 8000 patients on maintenance treatments. An early experience of 10 deaths in patients starting methadone has shaped the Victorian approach to treatment ever since (see Drummer 1990). Mean dose levels in Victoria have always been in the low range, around 40mg, and only reaching 50mg daily in recent years (NSW is around 70mg). We were told that there were essentially no public clinics in Melbourne and nearly all patients were treated in pharmacies from GP prescribers. This means no capacity for subsidised methadone treatment since all patients must pay for pharmacy dispensing which is normally from 3-5 dollars daily. Very few take-away doses were permitted (originally 3 single doses per month) although this is changing now under more flexible health department rules.<br /><br />Next we were informed that 33% of 193 authorised prescribers had no active patients. Another 33% had from 1 to 10 patients only while just 15% of the busier prescribers were treating 69% of Victoria’s patients. Thus most of the dependency treatment service in Victoria relies on just 27 individual doctors! By contrast in 2005 NSW had over 500 prescribers and 16,000 patients with no one doctor prescribing for more than 150 patients. In England all doctors can prescribe methadone if they wish to.<br /><br />Buprenorphine has had significantly greater uptake in Victoria than in the other states. After the first year of use (Jan 2002) there was just 10% of the total on buprenorphine according to some bar charts we were shown. By 2004 it rose to over 50% briefly and then dropped back slightly to 40:60 bup:meth since that time. One may speculate on the reasons, but they probably include the rigidity of the original methadone regulations in Victoria. There was widespread use of second daily buprenorphine even though this is not shown to be as effective as daily use.<br /><br />In Victoria even the more complex patients with extensive needs and poor resources were still mostly managed by GPs and pharmacists as there are no comprehensive clinics with access to counsellors, psychology, vocational support, social work, etc. Dr Lintzeris called this the ‘minimalist’ model. On the other hand, he told us that considering the state of play in Great Britain, there was simply no model or ‘system’ at all! This was not quite fair since he then showed a pie chart demonstrating that one quarter of patients in GP prescribing (nearly all ‘NHS’), another quarter in ‘shared care’ between formal clinics and GPs with fully 50% of all patients now in formal ‘specialist programs’ (Community Drug Teams). While some of these latter can formally supervise doses, few pharmacies give witnessed doses.<br /><br />Treatment access across the UK was highly variable and depended on GP willingness to prescribe. Waiting times for GPs is usually about 2 weeks but up to 3 months for Community Drug Team assessments. Proper, evidence based maintenance treatment (as per UK treatment guidelines) is the exception with most patients on low and reducing doses with sadly predictable results. A common practice is for 40mg daily to start with and reductions from there.<br /><br />GPs in the UK also commonly prescribe codeine, dihydrocodeine and buprenorphine but more due to personal preference rather than patient need. This applies equally to injectable methadone which comprised 10% of all opioid treatment prescriptions 10 years ago but is less than that now, partly due to the 1999 “Orange” guidelines which were sent to every practising GP in the UK. Methadone tablets are also less used now with about 95% of maintenance medication being methadone in liquid form, mostly the watery and bulky 1mg/1ml solution. Injecting of methadone is rare, as in Victoria, presumably due to dilution of doses which is almost universal. Whether such measures have more benefits than drawbacks on balance has never been tested scientifically. Thus it would seem prudent to consider diluting (‘expanding’) doses in special cases but not ‘across the board’ until such evidence is presented.<br /><br />Another disadvantage of non-supervised consumption in the UK is that the ‘black-market is flooded’. There is now a scheme whereby pharmacists are paid 1 to 2 pounds daily to administer doses of methadone; patients usually pay nothing. Over a third of patients attend once weekly (6 or 7 bottles dispensed) with a third attending daily (except Sunday) often taking a bottle home. Most of the reminder attend 2, 3 or 4 times weekly. There are no hard and fast rules to addiction treatment in the UK allowing much more professional freedom. Whether that is a good thing overall is a moot point considering the poor adherence to good prescribing practice over many years.<br /><br />The scientific evidence shows that if take-away doses and less supervision were linked to demonstrated progress, such as urine test results, this was the most effective intervention as ‘contingency management’ by another name.<br /><br />Dr Lintzeris mentioned the various risks of injecting methadone, overdoses, child deaths and the public perception of the drug treatment system generally. We were told that people could successfully inject the buprenorphine combination drug with naloxone, Suboxone (unpublished comparative study by Leslie Amass, CPDD 2000). Also Dr Lintzeris quoted reductions in the injecting of methadone in NSW and said that the reason behind this was not clear.<br /><br />Crushing of buprenorphine tablets has been advised by some parties yet evidence is limited on the practice. It would seem logical in some patients who had been caught diverting tablets, yet it clearly will not solve all the problems of buprenorphine administration.<br /><br />This returned us to some questions posed by Dr Hallinan before the seminar: Why do we have public clinics, private clinics and pharmacy dosing for supervised treatment in NSW? Along with prison programs, is this serendipitously world's best practice, or a ‘clumsy and vestigial hybrid’? Are we using a number of flexible treatment models for people in various circumstances, or limiting access to opioid maintenance treatments which could be given more effectively in another way? Later discussion and case studies dealt with issues surrounding "access block" in NSW.<br /><br />Summary by Andrew Byrne based on Dr Lintzeris’ power point presentation, questions on the night and some comments from Dr Richard Hallinan.Unknownnoreply@blogger.comtag:blogger.com,1999:blog-2135134153424193830.post-32771702771872900952007-11-20T20:50:00.000+11:002008-11-27T20:50:44.954+11:00Advances in assessment and treatments for infection with hepatitis C virus (HCV)Concord Seminar 20th November 2007<br /><br />Presenter: Professor Greg Dore, Viral Hepatitis Clinical Research Program, National Centre in HIV Epidemiology and Clinical Research.<br />Subject: Advances in assessment and treatments for infection with hepatitis C virus (HCV).<br /><br /><br />Topics: HCV epidemiology; treatment assessment; HCV treatment among methadone patients and current injecting drug users (IDU); strategies to improve HCV treatment outcomes; advances in HCV treatment and new research. <br /><br />Although there has been a drop in annual HCV notifications in Australia from 15,000 in the mid 1990s to 13,000 recently, it is unsure how much of this reflects a fall in incidence (new infections) and thus a success for existing harm reduction policies. As most HCV infections in injecting drug users (IDU) occur within the first few years of injecting, some more significant indicators may be reductions in new HCV notifications in the 15-19 year age group, and in HCV prevalence in young male IDUs attending needle syringe programs (NSPs) from 2001-2006. Such figures do indeed show a marked reduction, which is reassuring that overall notifications should decline further. <br /><br />It is possible that the lack of a fall in HCV prevalence in young female IDUs may reflect their "going second" in shared injecting situations, and/or sometimes having older male partners already at higher risk of having HCV.<br /><br />IDUs still constituted the majority (62%) of all acute or newly acquired infections in Australia (n = 474 in 2006), however this may be an underestimate as the source of infection is reported as unknown in 15%, and sexual in 5% (sexual transmission may occur where sexual practices involve blood but is unlikely in most "vanilla" sexual encounters / relationships). Tattoos account for about 8% and occupational exposure 2.5% of new cases. <br /><br />Overall HCV seroprevalence in people attending NSP remains high at 65%, and is somewhat higher again (75%) in MMT/BMT populations: ie about 30,000 of the circa 40,000 people in opioid replacement treatment in Australia. Of these, probably about 20,000 (50%) have chronic HCV (RNA-positive), about 10% of the total in Australia, making this an important point of access for HCV treatment.<br /><br />Mortality among people with HCV in Australia has a bimodal distribution, in the 5th and 8th decades of life, the former largely related to drug-related deaths among IDUs and the latter liver disease-related deaths in people born overseas, in HCV endemic areas. Liver disease-related deaths have risen since 1999, a trend perhaps "unmasked" by a fall of direct drug-related deaths as a result of the "heroin shortage".<br /><br />With cases of HCV cirrhosis in Australia predicted to rise to 12,000 by 2010, and twice that number by 2020, an aim is to be treating 6,000 people/year for HCV. Since April 2006, when the liver biopsy requirement for interferon-based treatment was dropped, treatment figures have risen from about 2,000 to 3,000/year. Liver biopsy was a major disincentive for many people. <br /><br />Sustained viral response SVR (persisting absence of viral RNA 6 months after treatment) is usually considered a cure of the viral infection, although not necessarily of the underlying liver damage. Occasional later relapses of HCV may represent reinfection with HCV in IDU. Over the last decade response rates to interferon-based treatment have improved, from about 10% SVR for interferon monotherapy to overall to over 60% SVR for combined pegylated interferon/ribavirin (PEG-IFN/RBV), ranging from 50 – 80% depending on genotype.<br /><br />Early studies of PEG-IFN·2a/RBV showed benefit of longer treatment (48 versus 24 weeks) and bodyweight-adjusted ribavirin dosing (up to 1200mg/day) for genotype 1, but not for genotypes 2 and 3. While early viral response (EVR) - defined as RNA undetectable or >99% decline in viral load at 12 weeks - increases the chances of SVR for genotype 1 to 72%, failure to achieve EVR almost inevitably predicts treatment failure.<br /><br />The bottom line for treatment is: 24 weeks PEG-IFN/RBV for genotypes 2 and 3; 48 weeks for genotype 1 if the person achieves EVR at 12 weeks. There is no evidence of any difference in efficacy between PEG-IFN·2a (Roche) and PEG-IFN·2b (Schering-Plough).<br /><br />Recent analysis suggests that people with genotype 1 who have a Rapid Viral Response (RVR) - HCV RNA undetectable at 4 weeks - may do just as well with 24 weeks as 48 weeks of PEG-IFN·2a/RBV, achieving SVR rates above 80%.<br /><br />At St Vincent’s Hospital in Darlinghurst, treatment completion rates rose from 55% 2000-02 to 74% in 2003-04, with drops in treatment discontinuations due to both non-response and to toxicity. This appears a trend to improvements in delivery of treatment.<br /><br />Results of treatment in current injectors are comparable to results among non injectors, and abstinence from IDU is not a pre-condition for subsidised treatment in Australia: nor are stage of fibrosis (was pre-2006); elevated ALT (was pre-2006); the presence of symptoms; low alcohol intake.<br /><br />There is some evidence of poorer treatment outcomes in people who continue to drink alcohol, but whether this is related to worsened treatment adherence or effects on viral replication is unclear. <br /><br />The current conditions for subsidised treatment eligibility in Australia (S100 Criteria) are:<br />· 18 years or older<br />· No evidence of de-compensated cirrhosis<br />· Must have chronic HCV infection (>6 months)<br />· Use double contraception where the patient is either a woman of child-bearing years or their male partner.<br />· No prior IFN-based HCV treatment<br /><br />Subsidised treatment costs the patient about A$30/month, (A$5/month for concession card holders) and this is probably as cheap as anywhere in the world. <br /><br />To be balanced against the curative potential of PEG-IFN/RBV are its toxicity (flu-like symptoms, depression, anaemia, lethargy) and the requirement for contraception during and 6 months following treatment. Apart from treatment eligibility, the stage of liver disease and prognosis the genotype and viral load, presence of co-morbidities, and work and family obligations have to be considered in treatment decision-making. There needs to be at least some treatment willingness and relative socio-behavioural stability, however with persistence and good support people with relative treatment contraindications can often be successfully brought through treatment.<br /><br />Greg Dore advocates some targeting of individuals with higher risk of progressive disease:<br />Higher likelihood of cirrhosis is predicted by:<br />· older age (> 40 years)<br />· duration of infection > 20 years<br />· heavy alcohol intake<br />· HIV or chronic HBV coinfection<br />· peripheral stigmata of CLD (spider naevi, palmar erythema)<br />· impaired hepatic synthetic function (low albumin, prolonged PT)<br />· AST / ALT ratio > 1.0<br />· AST / platelet ratio > 1.0 (<0.5 very unlikely to have cirrhosis)<br /><br />At the Byrne Surgery, about 50% of people with chronic HCV met similar criteria for higher risk of HCV progression, and have been specifically targeted for treatment, with 27 people having been treated since 2003. Of 20 liver biopsies among these higher risk people, 18 had at least moderate liver fibrosis.<br /><br />Although HIV and HBV co-infection are relatively uncommon in people with HCV infection, they are definite indicators of higher risk, and in many cases HCV treatment should be undertaken before HIV or HBV treatment.<br /><br />Phase II trials suggest benefit from triple therapies of IFN/RBV with protease inhibitors for chronic HCV and Phase II trials are due to start soon.<br /><br />Acute HCV can be treated with interferon monotherapy, with SVR rates of 80-90% in 3 months treatment, unless there is HIV co-infection or HCV genotype 1 with a high viral load. However, as about 25% of people spontaneously clear the virus (generally in the first 3 months after infection but up to 6 months and even later in a few cases) treatment of acute infection is usually deferred at least 3 months.<br /><br />Although sustained viral response rates at the Byrne surgery are high (71% overall, 81% for genotype 2/3) this is a case showing that things are not always so effective. This long-term MMT patient received HCV antiviral treatment in the setting of micronodular cirrhosis, Genotype 1a/1b, viral load 360,000 and pre-treatment alcohol use of 30-60g/day. This patient was overweight 105kg, a smoker (10 cigs/day) with shortness of breath on exertion, chronic airflow limitation (not taking medications), hypertension (Enalapril), probable ischaemic heart disease (chest tightness on stress test but no ECG changes; echocardiogram: LVH with moderate dilatation), osteoarthritis (diclofenac prn), a history of peptic ulcer disease (uses omeprazole prn).<br /><br />Despite these relative contraindications to treatment, this patient ceased drinking alcohol, and started combination treatment with IFN.2a/RBV, achieving rapid viral response (<600 ie qualitative RNA assay) at 5 weeks. RBV dose started with 1200mg/day and reducing to 800mg/day as haemoglobin dropped under 100, and was stopped for 5 weeks when the patient suffered severe nose bleeds (with normal BP 130/80; prothrombin time 1.1 and platelets acceptable at 81). Diclofenac was ceased, and ENT review showed a large vessel on the septum which was cauterised, packed with Chloromycetin for 3 days, with ongoing Vaseline use. <br /><br />After the patient had stoically endured 36 weeks of IFN.2a/RBV, and in view of the apparent rapid viral response, treatment was stopped at week 36, sadly with a rapid ALT and viral ‘flare’. The patient has since maintained alcohol abstinence and long term low dose interferon treatment is being considered.<br /><br />Issues arising from this case were the feasibility of treatment of "brittle" patients; drying of the nasal mucosa with the IFN/RBV; the pros and cons of NSAIDS for osteoarthritis in this situation; the possibility of viral escape with the interruption to RBV treatment and the wisdom of the decision to stop treatment early; whether endoscopy might have been done to exclude oesophageal varices before treatment; the benefits of going on the front foot in treating HCV in substance dependent people, who may rise to the challenge by achieving abstinence (in this case alcohol abstinence).<br /><br />Other questions arising in the second half:<br /><br />What about treating people with persistently high-normal ALT? A: there is some discussion about whether ALT reference ranges should be lowered, especially for women. A single normal ALT measurement is not helpful, as ALT typically waxes and wanes in chronic HCV, so ongoing monitoring at least is required. Although one would rather have a persistently lowish than a persistently very high ALT, ALT correlates poorly with disease activity, and the duration of HCV is an important consideration in assessing risk of disease progression.<br /><br />What is the role of abdominal ultrasound in assessing chronic HCV? A: mainly to exclude portal hypertension. Greg Dore often does not order this test. Newer methods for assessing fibrosis/cirrhosis by measuring the echo ‘stiffness’ of the liver may make ultrasound more useful.<br /><br /><br />Summary by Richard Hallinan, Greg Dore, Andrew Byrne.<br /><br /><a href="http://www.redfernclinic.com/">http://www.redfernclinic.com</a>Unknownnoreply@blogger.comtag:blogger.com,1999:blog-2135134153424193830.post-11871608862299371592007-09-25T18:44:00.000+10:002008-11-27T20:48:19.004+11:00Withdrawal management and detoxification-with a focus on complicated patients.Concord Seminar 25 September 2007<br /><br />Presenter: Dr Joanne Ferguson, FRANZCP, FAChAM, staff specialist psychiatrist, Rozelle Hospital. Medical Director, McKinnon Unit.<br /><br />Topic: Withdrawal management and detoxification-with a focus on complicated patients.<br /><br />Dr Ferguson stressed that the McKinnon Unit is not a “detoxification” ward but a medical unit which manages drug and alcohol withdrawals. The term detoxification is commonly used to refer to "chemicals, drugs, and food additives in the processed foods that we eat....", so that the general public, as well as our patients, may conceptualise drug withdrawal as a removal of such toxins: bringing to mind colonic irrigation, detox diets like Lemon Detox, herbal laxatives and high-fibre diets eliminating caffeine, meat and processed food, and associated treatments such as lymphatic drainage and massage.<br /><br />Dr Ferguson used clinical cases to illustrate principle and pitfalls of withdrawal management. Since detoxification is often undertaken in private with minimal problems and no interventions at all, she chose to deal with the more complicated cases such as those with dual diagnosis, dual or triple dependency and/or chronic infections. <br /><br />The first case was a 47 year old labourer who had relapsed after 3 years opioid abstinence. On presentation he was using MS Contin (slow-release morphine) 100mg to 500mg injected each day, to a maximum of up to 800mg in the 16 hrs before admission, with no withdrawal symptoms. He was also taking 10-15 x 5mg diazepam tabs daily (50-75mg daily). He was agitated and tremulous on arrival at the detox unit. <br /><br />The early symptoms and signs of enlarged pupils (possibly due to general sympathomimetic arousal), irritability, and anxiety were attributed to benzodiazepine withdrawal, where onset of symptoms is typically after 16 hours or so. Tremor is unusual as a symptom of opioid withdrawal, and might help point to benzodiazepine withdrawal.<br /><br />The benzodiazepine withdrawal regime at McKinnon Unit is to give 20mg diazepam 2nd hourly, to a maximum of 80mg in 24 hours, reducing to 60mg daily, then 35mg daily, 20mg daily then nil. Dr Ferguson told us that formal scoring of benzodiazepine withdrawal has not been shown to have any predictive value. <br /><br />Regarding opiate withdrawal there are usually early symptoms/signs such as enlarged pupils, sweating, pallor, agitation, goose flesh, lacrimation and runny nose. After that, nausea, melancholia and hyperalgesia can occur. At 36-48 hours, abdominal cramps, nausea, diarrhoea, mild leg aches are seen. By this stage, the enlarged pupils usually settle. Beyond this time, at 48-72 hours, there is more prominent aching of the leg and back muscles, abdominal pain and diarrhoea. <br /><br />For opiate withdrawals at McKinnon Unit the regimen is to give buprenorphine sub-lingual tablets 4mg +4mg+4mg in the first 24 hours. However, with a poor response to this drug initially, he needed a further 4mg making 16mg in the first day off heroin. (Buprenorphine qid dosing has more to do with service related issues than evidence base).<br /><br />In this case the patient suffered a protracted withdrawal syndrome, with the need to reintroduce buprenorphine on day 11. This was probably due to the mixed withdrawal syndrome, and possibly not adequately treating the opioid withdrawals early enough: it may be buprenorphine doesn't quite have the "grunt" to provide adequate symptom control in some cases.<br />The second case was a 24 year old methamphetamine-dependent man with schizophrenia, who lived with his family and was on disability support pension. He was taking Seroquel (quetiapine) 600mg bd, Solian (amisolpride) 800mg daily, Cipramil (citalopram) 40 mg daily, and had also been smoking a gram of “ice” daily for 8 months and taking Xanax (alprazolam) 2mg bd – prescribed by a GP. <br /><br />Withdrawal symptoms of agitation, hallucinations and religious preoccupation settled with diazepam 60mg in 24 hours. He then slept, was quiet and left at day 4 against medical advice, but clearly not happy with continuing treatment (and diazepam had been reduced by then). <br />Dr Ferguson posed the question of whether there is a withdrawal period from amphetamine use at all, or whether it is just a recovery period. Hence symptomatic treatment for agitation and sleeplessness may be provided with medications such as chlorpromazine, olanzapine and/or diazepam: there is some evidence of amphetamine users accessing olanzepine, as well as the more commonly available benzodiazepines, for self-medication of the amphetamine "come-down". The only thing that will help profound listlessness would be to extend the stimulant use. However, this is always self limited. <br /><br />The third case was a man aged 45 yrs with hep C, cirrhosis, diabetes and leg ulcers who had been drinking 90 to 120g alcohol daily with up to 15 x 5mg tabs diazepam daily. Single and on a pension, he was looking after his 13yo old daughter. He was a heavy tobacco smoker as well as using injected heroin every 2 weeks on pay days. <br /><br />The case illustrated how comorbid medical problems can have similar signs to alcohol withdrawal, including elevation of body temperature, and how to discriminate with a proper medical evaluation including blood counts and biochemical measures. Other issues were the need for nicotine replacement for tobacco withdrawal; whether agitation might be due to nicotine replacement or nicotine withdrawal; a possible preference for oxazepam over diazepam for severe liver failure with impaired hepatic drug metabolism (risk of over-sedation from accumulation of diazepam); a lower need for diazepam when unwell or drowsy.<br />A mild Alcohol Withdrawal Syndrome may not need any medication within the first 24 hours, after 2-3 days symptoms of anxiety, sweaty, headaches, insomnia, tremor, mild hypertension and tachycardia may be present. “Generally symptoms are mild and require little in way of medication” however medication eases withdrawal and improves outcome - diazepam and thiamine are the mainstay. There is no evidence of benefit from more than 100mg thiamine daily, however at least the first dose should be given intramuscularly, as after bouts of heavy alcohol use there may be chronic or acute diarrhoea, and oral absorption is often poor. For severe intoxication/withdrawal, for example for drinkers of methylated spirits, 100mg thiamine should be given intramuscularly for at least 3 days.<br /><br />More severe symptoms are dehydration, diarrhoea, anorexia, nausea, vomiting and weakness and very severe cases may have hypertension (diastolic of 120mmHg or greater can require antihypertensives) panic attacks, marked tremors, fever (however true fever is rare unless with an infectious cause). Seizures and delirium are a sign of treatment failure and should not occur when proper medical treatment available.<br /><br />Alcohol withdrawals can occur with relatively high blood alcohol levels in heavy drinkers, including those who have reduced their use - Dr Ferguson has seen a case of alcohol withdrawal with a BAL of 0.17, so one needs to assess baseline use and more recent use.<br />Alcohol Withdrawal Scales (AWS) are subjective, with infection/fever and other illnesses as potential confounders, and need to be used thoughtfully and in context. Further, AWS has poor correlation with BP/pulse. Providing diazepam only when AWS >5 means people can be significantly uncomfortable before can get treatment. A kinder alternative may be to treat as soon as the BP is elevated or at the first sign of tremor.<br /><br />The issue of using vigabantrin (Sabril) for alcohol withdrawal was raised as it may have fewer side effects but is currently only approved for resistant epilepsy. <br /><br />The fourth case was of recurrent withdrawal episodes in a 47 year old alcohol and opiate dependent man on pension living alone in a rental flat, a history of depression and hypothyroidism, and more than 10 admissions to hospitals in 12 months, usually through casualty distressed & unable to cope, out of medication in withdrawal, anxious, but also with several falls and injuries, complicated by MRSA infection, and recently shortness of breath with possible myocardial infarction.<br /><br />After prolonged withdrawals (80mgs diazepam for 3 days then reducing over 10 days) he was unable to go to rehabilitation as he was overwhelmed and unable to organise himself.<br />Issues raise by this case were: therapeutic nihilism - where feelings of despair, hopelessness in treatment providers augment the client's feelings of guilt, shame and hopelessness; and the ‘GOMER’ (get out of my emergency room) syndrome. The patient had some cognitive impairment but not so much to need involvement of the Guardianship Board to manage his affairs. Under the NSW Inebriates Act there has been a trial at Nepean Hospital of compulsory treatment for 2 weeks, with another 2 weeks following where necessary. Patients can also be sent to gazetted Psychiatric Hospital beds. This is not feasible for the great majority. <br />In general the patient needs to initiate treatment, and we need to recognise and accept the limits of what we can do, focus on symptom management not demand management and have a clear consensus of treatment aims, an agreed plan of treatment and a opt out phase.<br /><br />Dr Ferguson described protocols for withdrawal management at Rozelle Hospital. <br /><br />Opiate dependency: - buprenorphine 8-12 mg sublingual per day for 3-5 days, depending on opiate type and quantity. Reduce to 8/6/4/2/2 for last 2days. Symptomatic relief with metoclopramide (Maxalon), hyosine (Buscopan), diazepam (Valium).<br /><br />Alcohol: - diazepam (Valium), dose not set, related to dispensing and review issues, maybe 40mg/day and metoclopramide (Maxolon) and antihypertensive.<br /><br />Cannabis/THC: Symptoms of insomnia, agitation, irritable, appetite change, lasting 1-5 days, for which benzodiazepines - at lower doses than for alcohol withdrawal - , olanzapine (Zyprexa), mirtazapine (Avanza) may be used. There seems to be a consensus not to do inpatient withdrawal for THC, but McKinnon will do it for failed (and documented) outpatient withdrawal.<br />In order to access their services, there needs to be a phone assessment of demographics (do they live in the right area?); drug use and co morbidities; negotiation of a treatment plan (which MAY include withdrawal medication options) and then articulation of the plan: for admission (the person must phone daily at 7am until they can secure a place for admission); and/or outpatient appointments; documentation for MMT/BMT; mental health assessment; and/or other requirements eg plans for subsequent rehabilitation programmes.<br /><br />Some predictors of failure ambulatory treatment (as an outpatient) are (1) poor support of abstinence; (2) poor housing (or no housing); (3) multiple drug use, including withdrawal from one substance and use of others (except nicotine); (4) or severe symptoms of withdrawal.<br /><br />The question was raised why drug and alcohol practitioners in the community seldom have any joy "referring" their patients liaising directly with the staff of "detox" units, and do not receive discharge summaries as from most other hospital services. The answer may lie in the historical development of hospital drug and alcohol services using a psychiatric care model, with a primary client orientation and team based case, as well as possibly some resistance among nursing staff to perceived medical paternalism.<br /><br />In the second half there were a few case vignettes and selected scenarios:<br />"I went into hospital to come off alcohol and benzos, and they just gave me Normison and sent me home on the 3rd day ...". This was a 41yo woman with history of alcohol withdrawal fits, alcoholic hepatitis. Some questions raised were:<br /><br />1. If someone has a history of having fits while taking benzodiazepines, do they need admission for withdrawal management? A. not necessarily<br /><br />2. Why does anyone need to go into a detox unit to come off benzodiazepines? Surely you can just change them over to diazepam and reduce the dose, in the community. A: supervision issues.<br />Evidently this patient’s symptoms were assessed as mild in the first 48 hours, predicting little risk of complicated benzodiazepine withdrawal. However it appears to be an early discharge for alcohol withdrawal, depending on the alcohol use history given.<br /><br />"I get fits when I stop alcohol, but I'm not going back to that detox place - can't you just give me some Valium, Doc?" This was a 54 yo man on methadone, with hepatitis C, cirrhosis and ascites, presenting to a doctor in the community, with blood alcohol 0.06 and withdrawal symptoms of agitation and marked tremor. As alcohol withdrawal is dangerous, Dr Ferguson considered it medically strongly indicated to give some diazepam. However, some doctors may feels apprehensive about medico-legal consequences of giving diazepam to an intoxicated patient outside a supervised setting. It may be safest in small quantities, especially if supervised at the surgery, clinic or pharmacy. <br /><br />"I need to go somewhere to come off cannabis, but the rehab won't take me because I'm on methadone, and the detox unit say they don't do cannabis withdrawal...." - it was agreed that some people may need to remove themselves from a high exposure environment to stop cannabis use, and this may be difficult when the person in on MMT. Some "detox" units offer this service, while for others it is considered low priority.<br /><br />Andrew Byrne posed the question of when and why detoxification units started giving opiates to opiate addicts. Previously it was rather unusual, if not unheard of, rather like giving hospital brandy to alcoholics who were drying out. This changed the nature of the treatment from detoxification to ‘re-toxification’ in many or even most opiate admissions. This can even be the case in those intent on immediate abstinence. Especially with a very long acting drug such as buprenorphine, it ensures that detoxification does not even start until a few days after leaving the ward, quite the opposite of the traditional position. Was the decision to use buprenorphine in such situations taken to just to keep the patients quiet? Why not use methadone or morphine? Were there commercial considerations? The practice may offer patients a ‘taste’ of a possible maintenance treatments yet this they could just as easily obtain as out-patients, and most opiate addicts have tried such approaches. Dr Ferguson had no answer, nor did anyone else, it seems. This dramatic change in treatment policy seems to have happened without any discussion or most importantly, input from drug addicts themselves. The only justification we were told is that compliance and retention are now better, yet these were not tied to logical and practical patient goals, most notably opiate abstinence. <br /><br />Summary written by Richard Hallinan, Andrew Byrne, Judith Meldrum with help from Dr Joanne Ferguson’s power point presentation.Unknownnoreply@blogger.comtag:blogger.com,1999:blog-2135134153424193830.post-67294442227314376512007-07-31T18:30:00.000+10:002008-11-27T20:42:52.532+11:00Personality Disorders. 31 July 2007Concord Dependency Seminar 31 July 2007.<br /><br />PERSONALITY DISORDERS.<br /><br />Dr Glenys Dore, Senior Staff Specialist Psychiatrist, NSCCAHS<br /><br />In this seminar Dr Dore introduced us to what is sometimes a “no go zone” for health professionals involved in addiction treatment: Personality Disorders (PDs).<br /><br />People with Personality Disorders are “The Patients Psychiatrists Dislike” (Lewis & Appleby Br J Psych 1988), and workers in drug and alcohol will recognise these feelings: these patients are seen as difficult to manage, unlikely to arouse sympathy, annoying, not deserving of health resources, noncompliant, not accepting advice, having poor prognosis, their suicide attempts as “attention-seeking’ rather than genuine, their requests for admission as manipulative.<br /><br />Therefore, a Personality Disorder diagnosis may be seen as derogatory, pejorative and stigmatising. “What is conveyed…. is that the patient is difficult and probably unpleasant” (Gunn & Robertson Psychological Medicine 1976), with their symptoms seen as less genuine (Slavney & McHugh 1974; Thompson & Goldberg 1987).<br /><br />Before focusing on Antisocial PD and Borderline PD, the most common diagnoses in substance using populations, Dr Dore traced some of the development of ideas about what we now call personality.<br /><br />Hippocrates identified four elements in nature with four corresponding substances in human beings: Air, with Blood; Water, with Phlegm; Fire, with Yellow bile; Earth with Black bile. Galen later identified four corresponding “temperaments”: from blood, the Sanguine (confident, hopeful); from Phlegm, the phlegmatic (dull, sluggish); from bile, the Choleric (passionate) and from Black bile, Melancholic.<br /><br />Eysenck neatly resolved Galen’s four temperaments into two dimensions: introversion-extroversion along one axis and stable-unstable along the other. In this model, the “sanguine” person was extroverted and stable; the "phlegmatic" person stable but introverted; the "choleric" person extraverted and unstable; the "melancholic" person introverted and unstable (the psychotic person emerged out of this combination).<br /><br />Others have suggested a three or four dimensional approach. Cloninger’s model of personality, has four distinct “traits” of Temperament (Harm avoidance, Novelty seeking, Reward dependence and Persistence) and three “traits” of Character (Self-directedness, Cooperativeness, Self-transcendence). Temperament comprises basic emotions, the emotional core of personality, early emotional and behavioural dispositions whereas Character “mental self government”, “what a person makes of himself or herself intentionally”.<br /><br />For example, one of your correspondents is by temperament harm avoiding, novelty shy, aloof (not needing cuddles) and persistent……another almost the opposite. Both, of course, have Self-directed, Cooperative and Self-transcendent characters!<br /><br />DSM-IV is concerned less with theories and more with practical empirical descriptions. Thus, it uses a categorical rather than Dimensional approach, with 3 clusters - Cluster A, Odd or Eccentric; Cluster B, Dramatic, Erratic or Emotional and Cluster C, Anxious or Fearful - comprising a total of ten personality disorders (and a rag-bag category, as always in DSM, “not otherwise specified”).<br /><br />Personality Disorders are common in the general population (Antisocial PD = ASPD 4%, Borderline PD = BPD ~ 2%), and especially so in psychiatric populations and people with substance use disorders. Among people with a current alcohol use disorder:<br />30% have at least 1 PD; people with a current drug use disorder, 50% at least 1 PD. The ATOS study reported 80% of current heroin users with a PD, 33% Antisocial PD, 7% Borderline PD, 38% ASPD + BPD. In this study BPD was strongly related to suicide attempts, needle sharing, overdose risk, polydrug use, depression, psychological distress and poorer treatment outcomes (Darke et al. Drug & Alcohol Dependence 2004). Antisocial PD is associated with earlier onset drug use & IDU, more polydrug use, higher levels HIV risk-taking and poorer social functioning in patients on MMT (Henderson et al 2002 NDARC Monograph No. 49).<br /><br />Before labelling someone with a personality disorder (like "narcissistic" or "borderline") it is essential to be sure that they meet the general criteria of a personality disorder. Under the mnemonic PPAIIN, the pattern of inner experience & behaviour must be Persistent, Pervasive (with a broad range of personal & social impacts), from Adolescence onwards, causing Impairment, be Inflexible & maladaptive and Not due to mental disorder, medical condition, or substance use.<br /><br />Before concentrating on ASPD and BPD, Dr Dore introduced us to all the DSM PDs, for which ingenious psychiatry candidates have developed helpful mnemonics (listed in the Supplement to this summary on the Redfern Clinic Website, with some case examples).<br /><br />In Cluster A, the Odd or Eccentric group, are the Paranoid (Suspicious, Jealous, but not Psychotic or Unlawful); the Schizoid (Unemotional, Cold, Indifferent) and Schizotypal (Odd + Magical Beliefs, Behaviors, not Paranoid) types.<br /><br />Cluster A PDs have a higher incidence in families of schizophrenia patients, and are often antecedent for Psychotic disorders, including schizophrenia, delusional disorders and schizophreniform disorder. In these people, stress may trigger Brief Reactive Psychosis.<br /><br />Treatment options for cluster A include low dose antipsychotics and supportive psychotherapy, with openness, consistency, emphasising reality (paranoid), and social skills development (schizoid), and education on the interaction between substance use & psychiatric vulnerability.<br /><br />In Cluster C, the Anxious or Fearful group, are the Avoidant (Needs People But Fears Relationships); Dependent (Needs Relationships, Indecisive, Fears Abandonment) and Obsessive-Compulsive (Rigid, Perfectionist + Inefficient) types. The Passive-Aggressive PD (Negative Attitudes with Passive Resistance to Demands) was dropped from DSM-IV.<br /><br />Remember that Cluster-C PD are not the same as anxiety disorders, although these may co-exist. Anxiety disorders may respond to specific therapies.<br /><br />In Cluster B, the Dramatic, Erratic or Emotional group, are the ASPD (Aggressive, Unlawful, Impulsive); Borderline (Unstable, Chaotic, Impulsive, not Aggressive or Unlawful), Narcissistic (Self-Centered, Entitled, Lacks Empathy But Not Unlawful or Chaotic), and Histrionic (Dramatic, Seductive But not Chaotic) types.<br /><br />Many people will recognise the “narcissistic rage” of a person typically fragile at their core, the demands of specialness and entitlement belying a sense of inner inferiority. It was asked without irony how common Narcissistic PD is among CEOs. Sadly few people with Narcissistic PD go into psychotherapy, few improve over time. Histrionic PD might present as almost hypomanic.<br /><br />Briefly the DSM criteria for ASPD are: the individual is at least age 18 years, with evidence of Conduct Disorder with onset before age 15 years, and a pervasive pattern of disregard for and violation of the rights of others occurring since age 15 years, not exclusively during the course of Schizophrenia or a Manic Episode.<br /><br />As a general exclusion, the behaviours should not be better explained by another disorder, including a substance use disorder. ASPD may be over-diagnosed in SUD populations, because drug seeking behaviours, especially for illegal drugs, are likely to be considered “antisocial”.<br /><br />ASPD is more common in 1st-degree relatives of ASPD individuals, is associated with ADHD; the related Conduct Disorder is associated with erratic or inconsistent parenting and neglect. After 30 years of age there tends to be reduced antisocial behaviour (crime, promiscuity) and reduced substance use.<br /><br />Dr Dore gave the example of a man who had a history of fights, truancy, theft, near expulsion from school, drug use and dealing, addiction to heroin, benzodiazepines, cannabis, with alcohol use, and by age 19, three counts of murder. When seen at age 36 yrs, he was married, with a child, and much settled.<br /><br />Heroin users with ASPD respond as well as other heroin users to opioid pharmacotherapy (similar retention in treatment, methadone dosage, improvement in heroin use) however with poorer social functioning (Darke et al 1996; Darke et al 1994; Gill et al 1992; Rouser et al 1994)<br /><br />Spot the diagnosis: “On return from your last holiday, your patient informed you that she smashed up her goldfish bowl and flushed her much-loved goldfish down the toilet, killing them. She has since replaced them.”<br /><br />Marsha Linehan (1993), the guru of Dialectical Behavior Therapy, gives us an unforgettable image:<br /><br />“Borderline individuals are the psychological equivalent of the 3rd-degree burn patient. They simply have, so to speak, no emotional skin. Even the slightest touch or movement can create immense suffering….”<br /><br />Briefly the DSM criteria for Borderline PD are: A pervasive pattern of instability of interpersonal relationships, self-image and affects, and marked impulsivity beginning by early adulthood, which may include: frantic efforts to avoid real or imagined abandonment; unstable and intense interpersonal relationships alternating between extremes of idealization and devaluation; impulsiveness in spending, sex, substance abuse, shoplifting, reckless driving, binge eating ; recurrent suicidal threats, gestures, or behaviour, or self-mutilating behaviour; intense episodic dysphoria, irritability, or anxiety; chronic feelings of emptiness; inappropriate, intense anger or lack of control of anger; transient, stress-related severe dissociative symptoms or paranoid ideation. (see supplement for full criteria <a href="http://www.redfernclinic.com/c/2007/08/personality-disorders-supplement.php4">http://www.redfernclinic.com/c/2007/08/personality-disorders-supplement.php4</a>).<br /><br />People with BPD may suffer from an almost murderous rage. Does “cutting” serve as emotional release or self punishment? Their feelings may swing pendulum like between love and hate, the pedestal and resentment. There is a poor sense of identity, of who/what they are.<br /><br />BPD is characterised by recurrent suicidal threats, gestures, or behaviour, or self-mutilating behaviour, and although 90% improve despite multiple suicidal episodes, the stark reality is that 10% will complete suicide. Like ASPD, BPD tends to improve with age: by age 35 - 40 years: 75% have close to normal function, with less impulsivity (suicidality, self mutilation), better interpersonal relationships (less stormy relationships, less devaluation/sadism/manipulation) and people learn how to avoid emotional triggers. (Paris J. Canadian Medical Association Journal 2005)<br /><br />In managing patients with PDs, especially BPD, it is important to bear in mind the concept of Transference, whereby unresolved feelings about important figures from the patient’s past are revealed in the patient’s transference towards the therapist.<br /><br />Common defense mechanisms allow the person to defend against threatening or anxiety-provoking situations: splitting, idealisation, denigration, externalisation, projection, denial, acting out, repression.<br /><br />If this seems too high falutin, we can at least identify the tactics. The person may stone- wall (allows no choice other than his/her position), attack (“You’re not the caring doctor I thought”....“I’ll take you to HCCC”....“I’ll kill myself”) or trick (manipulating the facts, making surprise demands) (from Ury William. Getting Past No: Negotiating With Difficult People).<br /><br />The therapist's counterpart to transference is "Countertransference". They may themselves fall into the role of victim (feeling helpless, worthless, distant, withdrawn), of abuser (getting angry, retaliating, rejecting, cancelling appointments, "throw off program") or the role of rescuer ("only I understand"; unfair criticism of colleagues, extra appointments, late night calls, inappropriate prescribing, even sexual relationship).<br /><br />In balancing Countertransference, remember there is a "zone of helpfulness" between overinvolvement and underinvolvement.<br /><br />In managing your reactions, remember people are often trying to provoke reaction - they know your hot buttons. It is tempting to strike back, to break off the relationship, or to give in – the latter rewards bad behaviour, encourages same tactics in future, damages your reputation (weak, soft touch) and may compromise safety<br /><br />Some tips:<br /><br />• Try not to react, remain empathic and non-judgmental,<br />• “Go to the balcony”, either actually or mentally.<br />• “Step to their side” (you can't reason with a non-receptive patient, give a full respectful hearing<br />• Acknowledge (don’t dismiss patient as irrational, acknowledge his/her point & feelings, if appropriate offer an apology)<br />• Use active listening (eye contact, empathic, reflective listening, paraphrase, seek clarification<br />• Buy time to think (pause & say nothing, “rewind the tape, ask for clarification, take time out, delay the decision)<br />• Try to understand transference-countertransference issues.<br />• Debrief with colleagues<br /><br />Some rules for yourself:<br /><br />• Acknowledge their position, even if don’t agree with it (agree wherever you can)<br />• Express your views clearly without provoking (acknowledge negative impacts of your decision, acknowledge your differences, speak about your responsibilities, mention duty of care, Guidelines, Dept of Health etc)<br />• Negotiate a way forward (treatment contracts can help)<br /><br />The focus of treatment for BPD may be the BPD itself, or co-morbid Axis I, II disorders, and should include safety assessment and risk management.<br /><br />A suicide/violence risk assessment distinguishes between plan and intention. Watch out for a recent mental state change. Management includes a crisis plan in collaboration with other (clinicians and family), increasing patient responsibility (exploring alternatives to self harm, self soothing techniques), consulting with colleagues if high risk, with medication and/or hospitalisation if needed. It is crucial to document your assessment and plan: remember the pain of writing a "Dear Coroner" letter.<br /><br />Pharmacotherapies for BPD may be used with the aim of symptomatic relief: for affective dysregulation, impulsive-behavioural dyscontrol, or cognitive perceptual symptoms (suspiciousness, referential thinking, paranoid ideation, illusions, derealisation, depersonalisation, hallucinations). Treatments may include SSRIs or venlafaxine, low dose antipsychotics (higher doses if psychotic), Mood Stabilisers. ECT may be used if there is co-morbid severe axis I depression.<br /><br />Dialectical Behaviour Therapy is a three pronged approach<br /><br />• Accepting patients just as they are within a context of trying to teach them to change<br />• Supportive acceptance; validation<br />• Confrontation & change strategies (individual or group work towards emotion regulation, improved interpersonal effectiveness, distress tolerance, core mindfulness, self-management skills) (Linehan M. CBT of Borderline PD 1993)<br /><br />Principles of work with BPD (After Gabard 1994) are<br /><br />• Establish a stable framework/structure predictable (eg frequency, length sessions)<br />• Take an active stance: validate, affirm<br />• Contain the anger & self destructing behaviours (soothe, validate, risk assessment, limit behaviour; problem solve)<br />• Establish the connection between feeling & actions<br />• Set limits on problem behaviours<br />• Maintain a "here & now" focus<br />• Monitor countertransference feelings<br />• Risk Management<br /><br />Dr Dore highly recommended “Getting Past No: Negotiating With Difficult People”, a book by Ury William.<br /><br /><br />Summary by Richard Hallinan based on the Concord presentation by Dr Glenys Dore.<br />Supplement with helpful diagnostic mnemonics <a href="http://www.redfernclinic.com/c/2007/08/personality-disorders-supplement.php4">http://www.redfernclinic.com/c/2007/08/personality-disorders-supplement.php4</a>Unknownnoreply@blogger.comtag:blogger.com,1999:blog-2135134153424193830.post-46431815791233372432007-07-31T18:16:00.000+10:002008-11-27T20:40:29.356+11:00Personality disorders (by Dr Glenys Dore) supplementary notes.Concord Dependency Seminar 31 July 2007.<br /><br />PERSONALITY DISORDERS<br /><br />Dr Glenys Dore, Senior Staff Specialist Psychiatrist, NSCCAHS<br /><br /><br />Summary Supplement<br /><br />Paranoid personality disorder: SUSPECT (four criteria)<br /><br />S (1) Suspicious of others<br />U (5) Unforgiving (bears grudges)<br />S (7) Spouse fidelity suspected<br />P (6) Perceives attacks (and reacts quickly)<br />E (2) “Enemy or friend” (suspects associates & friends)<br />C (3) Confiding in others feared<br />T (4) Threats perceived in benign events<br /><br />Mrs F complained that people at work disliked her and she contemplated seeking legal advice as she thought they wanted her to leave. She had prolonged disagreements with the pay office about salary and conditions. When she requested a change of appointment with her doctor she “knew” it would be rejected despite it being offered, and complained bitterly about inflexible health professionals” Harari & Meares 2001<br /><br />Schizoid personality disorder: DISTANT (four criteria)<br /><br />D (7) Detached or (flattened) affect<br />I (6) Indifferent to criticism and praise<br />S (3) Sexual experiences of little interest<br />T (2) Tasks (activities) done solitary<br />A (5) Absence of close friends<br />N (1) Neither desires nor enjoys close relations<br />T (4) Takes pleasure in few activities<br /><br />Schizoid personality disorder<br /><br />Marjorie, a nurse, worked in the night shift in a small hospital. She lived alone with her 6 cats and saw her family only on Christmas Day, an event which she found most anxiety-provoking. Born of elderly parents, she had always been quiet and remote, a compliant child who seemed to need no company. In adult life she found it difficult to understand other people’s need for friends and believed that an emotional life was ‘unnecessary’. Harari & Meares 2001<br /><br />Schizotypal personality disorder: ME PECULIAR (five criteria)<br /><br />M (2) Magical thinking or odd beliefs<br />E (3) Experiences unusual perceptions<br />P (5) Paranoid ideation<br />E (7) Eccentric behaviour or appearance<br />C (6) Constricted (or inappropriate) affect<br />U (4) Unusual (odd) thinking and speech<br />L (8) Lacks close friends<br />I (1) Ideas of reference<br />A (9) Anxiety in social situations<br />R (10) Rule out psychotic disorders and pervasive developmental disorder<br /><br />Avoidant personality disorder: CRINGES (four criteria)<br /><br />C (2) Certainty (of being liked required before willing to get involved with others)<br />R (4) Rejection (or criticism) preoccupies one’s thoughts in social situations<br />I (3) Intimate r’ships (restraint in intimate relationships for fear of being shamed)<br />N (5) New interpersonal relationships (is inhibited in)<br />G (1) Gets around occupational activity (involving significant interpersonal contact)<br />E (7) Embarrassment (potential) prevents new activity or taking personal risks<br />S (6) Self viewed (as unappealing, inept or inferior)<br /><br />Dependent personality disorder: RELIANCE (five criteria)<br /><br />R (1) Reassurance (required for decisions)<br />E (3) Expressing disagreement difficult (due to fear of loss of support or approval)<br />L (2) Life responsibilities (needs to have these assumed by others)<br />I (4) Initiating projects difficult (due to lack pf self confidence)<br />A (6) Alone (feels helpless and discomfort when alone)<br />N (5) Nurturance (goes to excessive lengths to obtain nurturance and support)<br />C (7) Companionship (another relationship is sought urgently when close relationship ends)<br />E (8) Exaggerated fears of being left to care for self<br /><br />Obsessive-compulsive personality disorder: LAW FIRMS (four criteria)<br /><br />L (1) Loses point of activity (due to preoccupation with detail)<br />A (2) Ability to complete tasks (compromised by perfectionism)<br />W (5) Worthless objects (unable to discard)<br />F (3) Friendships (and leisure activities) excluded (due to a preoccupation with work)<br />I (4) Inflexible, scrupulous, overconscientious (on ethics, values, or morality, not accounted for by religion or culture)<br />R (6) Reluctant to delegate (unless others submit to exact guidelines)<br />M (7) Miserly towards self and others<br />S (8) Stubbornness (and rigidity)<br /><br />Histrionic personality disorder: PRAISE ME (five criteria)<br />P (2) Provocative (or sexually seductive) behaviour<br />R (8) Relationships (considered more intimate than they are)<br />A (1) Attention (uncomfortable when not the centre of attention)<br />I (7) Influenced easily<br />S (5) Style of speech (impressionistic, lacks detail)<br />E (3) Emotions (rapidly shifting and shallow)<br />M (4) Made up (physical appearance used to draw attention to self)<br />E (6) Emotions exaggerated (theatrical)<br /><br />Narcissistic personality disorder: SPEEECIAL (five criteria)<br /><br />S (3) Special (believes he or she is special and unique)<br />P (2) Preoccupied with fantasies (of unlimited success, power, brilliance, beauty or ideal love)<br />E (8) Envious (of others, or believes others are envious of him/her)<br />E (5) Entitlement<br />E (4) Excess admiration required<br />C (2) Conceited (grandiose sense of self importance)<br />I (6) Interpersonal exploitation<br />A (9) Arrogant (haughty)<br />L (7) Lacks empathy<br /><br />Antisocial personality disorder: CORRUPT (Three criteria)<br /><br />C (1) Conformity to law lacking<br />O (6) Obligations ignored<br />R (5) Reckless disregard for safety of self or others<br />R (7) Remorse lacking<br />U (2) Underhanded (deceitful, lies, cons others)<br />P (3) Planning insufficient (impulsive)<br />T (4) Temper (irritable and aggressive)<br /><br /><br /><br />A Quick Guide to the Personality Disorders (adapted from "DSM Made Easy", an excellent reference tool for the busy clinician!)<br /><br />"DSM-IV lists 10 personality disorders.... divided into three clusters, A, B, and C........ Five of the 10 have been studied reasonably well and therefore have greater validity than the rest: antisocial, borderline, obsessive-compulsive, schizoid, schizotypal."<br /><br />Cluster A: "withdrawn, cold, suspicious, or irrational."<br /><br />Paranoid Personality Disorder:....."distrustful and suspicious of others, whose motives are seen as malevolent."<br /><br />Schizoid Personality Disorder:..... "isolated from social relationships and shows a restricted emotional range in interpersonal settings."<br /><br />Schizotypal Personality Disorder:....... "isolation and discomfort with social relationships, as well as perceptual or cognitive distortions and peculiar behaviour."<br /><br />Cluster B: "dramatic, emotional, and attention-seeking.....moods are labile and often shallow.......often have intense interpersonal conflicts."<br /><br />Antisocial Personality Disorder:..... "Before age 15, for 12 months or more the patient [satisfied criteria for Conduct Disorder]...repeatedly violated rules, age appropriate societal norms, or the rights of others.... Since age 15, the patient has shown disregard for the rights of others in a variety of situations."<br /><br />Borderline Personality Disorder: ......"unstable impulse control, interpersonal relationships, moods, and self-image."<br /><br />Histrionic Personality Disorder: ...... "emotional excess and attention-seeking behaviors are present in a variety of situations"<br /><br />Cluster C: "anxious and tense, ......... often overcontrolled."<br /><br />Narcissistic Personality Disorder:...... "grandiosity (fantasized or actual), lack of empathy, and need for admiration"<br /><br />Avoidant Personality Disorder:........."social inhibition, hypersensitivity to criticism, and feelings of inadequacy are present in a variety of situations"<br /><br />Dependent Personality Disorder:..... "a need to be taken care of leads to clinging, submissive behaviour and fears of separation that are present in a variety of situations"<br /><br />Obsessive-Compulsive Personality Disorder:....... "a preoccupation with control, orderliness, and perfection overshadow qualities of efficiency, flexibility, and candour."<br /><br />Generic Criteria for Personality Disorders<br /><br />1. A lasting pattern of behaviour and inner experience that markedly deviates from norms of the patient's culture..... evident in at least two of these areas:<br /><br />• Affect<br />• Cognition<br />• Impulse control<br />• Interpersonal functioning<br /><br />2. This pattern is fixed and affects many personal and social situations ....[and] causes clinically important distress or impairs work, social, or personal functioning.<br /><br />3. This pattern has lasted a long time.......with roots in adolescence or young adulthood.<br /><br />4. It isn't better explained by another mental disorder ......[and] isn't directly caused by a general medical condition or by the use of substances, including medications.<br /><br /><br /><br /><br />Full Diagnostic Criteria for Borderline Personality Disorder<br /><br />A pervasive pattern of instability of interpersonal relationships, self-image and affects, and marked impulsivity beginning by early adulthood and present in a variety of contexts, as indicated by 5 (or more) of the following:<br /><br />• Frantic efforts to avoid real or imagined abandonment (do not include suicidal or self-mutilating behaviour covered in criterion 5).<br /><br />• A pattern of unstable and intense interpersonal relationships characterized by alternating between extremes of idealization and evaluation.<br /><br />• Identify disturbance: persistent and markedly disturbed, distorted, or unstable self-image or sense of self (eg. feeling like one does not exist or embodies evil).<br /><br />• Impulsiveness in at least two areas that are potentially self damaging (eg. Spending, sex, substance abuse, shoplifting, reckless driving, binge eating – do not include suicide or self –mutilating behaviour covered in criterion 5).<br /><br />• Recurrent suicidal threats, gestures, or behaviour, or self-mutilating behaviour.<br /><br />• Affective instability: marked reactivity of mood (eg. intense episodic dysphoria, irritability, or anxiety) usually lasting a few hours and only rarely more than a few days.<br /><br />• Chronic feelings of emptiness.<br /><br />• Inappropriate, intense anger or lack of control of anger (eg. Frequent displays of temper, constant anger, recurrent physical fights).<br /><br />• Transient, stress-related severe dissociative symptoms or paranoid ideation.<br /><br />Full Diagnostic criteria for 301.7 Antisocial Personality Disorder<br /><br />A. There is a pervasive pattern of disregard for and violation of the rights of others occurring since age 15 years, as indicated by three (or more) of the following:<br /><br />• failure to conform to social norms with respect to lawful behaviours as indicated by repeatedly performing acts that are grounds for arrest<br />• deceitfulness, as indicated by repeated lying, use of aliases, or conning others for personal profit or pleasure<br />• impulsivity or failure to plan ahead<br />• irritability and aggressiveness, as indicated by repeated physical fights or assaults<br />• reckless disregard for safety of self or others<br />• consistent irresponsibility, as indicated by repeated failure to sustain consistent work behaviour or honour financial obligations<br />• lack of remorse, as indicated by being indifferent to or rationalizing having hurt, mistreated, or stolen from another<br /><br />B. The individual is at least age 18 years.<br /><br />C. There is evidence of Conduct Disorder with onset before age 15 years.<br /><br />D. The occurrence of antisocial behaviour is not exclusively during the course of Schizophrenia or a Manic Episode.Unknownnoreply@blogger.comtag:blogger.com,1999:blog-2135134153424193830.post-2456967071323800572007-05-22T18:33:00.000+10:002008-11-27T20:37:15.603+11:00The Interpretation of Urine Toxicology in Dependency Treatment. Principals and Pitfalls.Concord Seminar 22 May 2007<br /><br />The Interpretation of Urine Toxicology in Dependency Treatment. Principals and Pitfalls<br /><br />Speaker: Dr John Lewis, Toxicology Unit, Pacific Laboratory Medicine Services<br /><br />Dear Colleagues,<br /><br />Dr Lewis is one of the world’s leading experts in drug testing. His speaking manner combines what T. S. Eliot might have termed a lugubrious drollery with a profound grasp on his subject. It is easy to be light-hearted about ‘piss tests’ but it is also deadly serious if your own job, drivers licence or liberty depend upon such a result. <br /><br />We were reminded first up what urine testing can NEVER determine with any accuracy: (1) the dose, (2) the time it was taken or (3) the pharmacological effect of any substance being tested. <br /><br />The most common drug assays they perform are for methadone and metabolites, cannabinoids, opiates, cocaine, benzodiazepines and amphetamines. Barbiturates often omitted these days since their illicit use seems to have ceased for all practical purposes. The term ‘amphetamine type substances’ (ATS) is now superseding ‘sympathomimetic amines’. This group includes dexamphetamine, methylamphetamine, ecstasy (MDMA), methylenedioxyamphetamine (MDA), and other ‘designer’ drugs such as paramethoxyamphetamine (PMA) and their metabolites, but also ephedrine, pseudoephedrine. One needs to know the particular immunoassay ‘kit’ being used to be sure what exactly is detected and at what level. <br /><br />Laboratories are asked to perform tests both in a clinical setting as well as for forensic, workplace or medico-legal reasons. For clinical purposes a cost effective and fast turn-around time approach is used. This starts with an inexpensive immunoassay which is very sensitive for most of the drugs being tested for, but generally not specific. Hence a negative batch of tests can yield a fast, efficient response to the clinician. Positive immunoassay results for any of the drug groups (or negative for methadone) may indicate further testing, typically using GCMS (gas chromatography/mass spectrometry), which is considered the ‘gold standard’. Although thin layer chromatography (TLC) is not commonly used nowadays, Dr Lewis says it still has a place: it presents information on a large range of drugs to view at a single glance, and is inexpensive. Because the TLC depends upon the human factor of recognising patterns, it is subjective and unless the spot patterns correspond to known medication, confirmatory testing by mass spectrometry is usually conducted. Although it is not used for medico legal work, it still has a place in clinical settings, as an adjunct to mass spectrometry in presumptively identifying a wide range of therapeutic substances not amenable to immunoassay.<br /><br />In particular cases there will need to be specific tests done, especially for suspected drug use which may not be detected by the usual immunoassays. These include tests for doctors, nurses or other health care workers on conditional registration due to drug use. Such drugs include pethidine, tramadol and the short acting anaesthetic propofol. Abuse of these drugs outside the medical setting is exceptional. <br /><br />Note that buprenorphine is also hard to detect by simple methods. Although there is an immunoassay for the drug, toxicologists must be aware of possible false positives from a number of unrelated therapeutic substances. However, like methadone, when the dose is taken under supervision such testing is less important than, say, in England where much treatment is unsupervised and testing for the prescribed medication can be crucial in determining compliance and overall stability. <br /><br />Dr Lewis then detailed the limitations and strengths of modern immunoassays in determining a class of drug but only in two cases can they detect specific metabolites, EDDP (for methadone) and 6-mono acetyl morphine (heroin). The value of a negative test was pointed out. We were reminded that testing was almost pointless in hospital casualty cases: for overdoses, the results are usually not available until either the patient is dead or else recovered. Also, medications are used so routinely and such patients may have injuries necessitating local anaesthetics, dressings, iodine, etc in the course of their treatment in the casualty ward that results are close to meaningless. <br /><br />Specifically, Dr Lewis said that positive opiate and ATS immunoassays should be taken with caution as there are many causes of false positives. These include poppy seeds, cough mixtures, decongestants and common analgesics. Dr Lewis told us that his own urine remained positive for ‘opiates’ for nine days after a dose of the cough suppressant pholcodine. The main value of these screening tests is when the result is negative. Note that ‘opiate’ immunoassays do not detect the ‘opioids’ methadone, buprenorphine, pethidine and others. Oxycodone has only a very weak response to “opiate” immunoassays.<br /><br />We were then shown the plates used for thin layer chromatography and a list of 20 common drugs which can be definitively determined using this method (eg. morphine, codeine, oxazepam, pseudo-ephedrine, paracetamol and nicotine). GCMS was then described in response to a question from the floor. In essence it appears that there are two properties of each substance which are identified in the method, causing a unique fingerprint from the two derived figures. It is more expensive than other methods, but more accurate and specific, being able to detect both the original base compound as well as ‘derivatised’ products. <br /><br />Then we had a brief tutorial on the use of testing for alcohol consumption. Everyone knows about breath testing, but 5% of alcohol is excreted in the urine and there is a direct correlation between plasma and urine alcohol concentration of 1.3:1. However, due to the short half life of alcohol, such testing is only of any use within hours of the drug use. And, as with other drugs, a certain level could be associated with a small amount of drug used very recently, or equally, a large amount used quite some time before.<br /><br />There are also unexpected false positives, including a case Dr Lewis described where urine from a diabetic in a rehabilitation facility had undergone fermentation (probably by yeasts) before being tested; the calculated blood alcohol concentration (0.34) would have been lethal. A less ‘gross’ error might not have been discovered, and this would have led to the automatic expulsion of the person from the rehab facility. <br /><br />Tests for cannabis are of limited value since, for most, its use is not relevant to the treatment or supervision being given. Hence Dr Lewis only performs cannabis tests when specifically requested, such as in patients being treated for cannabis dependence, to assess progress. <br /><br />We were then taken through some metabolic pathways. Heroin breaks down within minutes into 6-acetyl morphine, then to morphine. This then is broken down into morphine-6 or -3 glucuronide which are excreted. Codeine is largely conjugated into codeine-6 glucuronide, but importantly, a small proportion is transformed into morphine. A positive test for morphine can therefore sometimes occur due to codeine use (but not the other way around). A warning: most tests underestimate the amount of codeine in urine, as the metabolite codeine-6 glucuronide is hard to "bust" into codeine, which can be detected. It is important to know the relative amounts of morphine and codeine in a urine sample as the ratios affect correct interpretation as to what may or may not have been ingested.<br /><br />Diazepam is broken down into another active metabolite, oxazepam. This can occur via two intermediaries, nordiazepam and temazepam. Most of the common sedatives and related drugs such as clobazam will show up as benzos on the initial immunoassay. However, specific confirmatory testing must be done when clobazam is used in therapeutic trials to test against ‘street’ benzos. <br /><br />Stimulants were then covered including the new definition of ice in an age of global warming (ice-bergs and all!). Amphetamine was first synthesised by the Germans in 1887. It was heavily marketed in the US in the 1930s as ‘Benzedrine’. Methylamphetamine is easier to manufacture, especially if one has the base product pseudoephedrine. We were then told that the latest ‘craze’ for stimulants is purely based on stronger, highly purified drug being available in the form of ‘crystal meth’ or ‘ice’. Methylamphetamine powder is a salt, "crystal" a highly purified salt, and "base" is an oil. Urine testing cannot distinguish between them as these are the same drug. While Dr Lewis’ lab has found 2005 was the year with highest mean amphetamine levels, in 2006 the maximum levels found each week continued to climb to being 5 fold the 2003 levels. While these are dramatic findings, it is hard to know their significance overall except to imply that some users are taking very large amounts of methylamphetamine, viz, “ice”.<br /><br />Cannabis has many metabolites which are detected on screening, and confirmed with carboxy –THC on GCMS. It is very lipophilic, and gets stored in the fat cells of the body. Cannabinoid urine tests may be negative within a few hours of a single smoke; daily use may take many days, and heavy use a month or more. If a high level is found then it is easy to know that there is continuous use. Carboxy-THC: creatinine ratios can indicate increasing or decreasing use (see case vignettes below).<br /><br />Then there was a discussion about laboratory ‘cut-offs’ which are essential for legal purposes, but less meaningful for clinical purposes, except to reduce the numbers of false positives. Cut-offs are also necessarily somewhat arbitrary, like the drink driving limits - and can vary from place to place or from time to time. Currently 50ng/ml is used for immunoassays of cannabinoids, and 15 ng/ml for the specific GCMS for carboxy-THC (plus or minus a figure for lab uncertainty; this means an actual cut off of around 18-19 ng/ml). Dr Lewis believes there is a case for higher cut-offs to be used for cannabinoids, to identify substantial cannabis use, rather than low level or more importantly residual drug from previous heavy use.<br /><br />Some case vignettes in the second half illustrated common problems. Three patients with positive immunoassay for opiates claimed only to have taken codeine-based analgesics. One had codeine and morphine on GCMS, and this could be explained by metabolism of codeine to morphine, or other sources or morphine such as poppy seeds, morphine sulphate etc. Another had urine positive for morphine, and negative for codeine: this could occur if there was extensive metabolism of codeine to morphine (for example by cytochrome CYP2D6 ultrarapid metabolisers) and especially if the laboratory test underestimated the amount of codeine (see above). In the last case, urine was positive for morphine and monoacetyl-morphine: the latter can only come from heroin use.<br /><br />In a case of roadside drug testing, a woman justified her positive salivary cannabis test by saying "I never smoke pot, but my partner smokes it all the time". Dr Lewis explained that this test does not pick up metabolites of THC, only the parent drug, and is not very sensitive, missing a large proportion of cannabis users (as reported by the European ROSITA study). Thus passive smoking could not cause a positive test. A man on methadone, who had not had a positive urine test for many years, blamed his positive urine cannabinoid test on his partner, who ‘smoked 30 cones each day’. A positive immunoassay test result is unlikely to be a result of passive inhalation. It is more likely be a false positive due to other medication, cross contamination or else laboratory error. <br /><br />Dr Lewis described the benefits of using carboxy-THC:creatinine levels to help allow for variation in urine concentrations due to level of hydration. Cases were shown from the Drug Court, where declining THC:creatinine ratios were consistent with ongoing abstinence; in another case a spike in ration of THC:creatinine led to punitive action, but might have been explained by the person going to the gym, and mobilising cannabinoids stored in fat cells.<br /><br />Another case from the Drug Court showed how the sequence of appearance or disappearance of diazepam metabolites (nordiazepam, oxazepam and temazepam) could be used to make inferences about recent diazepam use. In this case, as in almost every example discussed, Dr Lewis was able to give examples of exceptions, where other causes than the most obvious might account for the result. So urine tests should never be interpreted uncritically by untrained people.<br /><br />In another case, a worker was suspended for producing "dilute urine" (wrongly described as a "false negative urine test") because of low creatinine urine (1.4 mmol/L), and allegedly told he would need to produce two urine tests with creatinine higher than 5 mmol/L. However, this worker's serum creatinine was low owing to lean body build, while urea, electrolytes, specific gravity, osmolality were consistent with physiological urine. THC:creatinine ratios might help adjust for hydration (some people deliberately drink lots of water to dilute their urine) but could also discriminate against people with naturally low creatinine. A urine creatinine level as low as 0.9 mmol/L is physiologically achievable. Below this suggests the likelihood, and below 0.5 mmol/L the near certainty, of external interference with the sample, usually meaning dilution after urination. <br /><br />Laboratories and clinicians need to be careful with the information they give as employers may misinterpret loose terminology. <br /><br /><br />Comments by Andrew Byrne, Richard Hallinan and Judith Meldrum, from Dr Lewis’ talk and power point presentation.Unknownnoreply@blogger.comtag:blogger.com,1999:blog-2135134153424193830.post-11821826544564496892007-03-20T19:06:00.000+11:002008-11-27T20:12:59.716+11:00Methadone side effects, separating fact and fiction.Concord Dependency Seminar, Tuesday 20 March, 2007<br /><br />"Methadone side effects, separating fact and fiction".<br /><br />The evening began with Dr Adam Winstock's overview of a recent study of about 1000 patients on methadone and buprenorphine, suggesting high rates of side effects: sweating, sexual dysfunction, sedation and constipation. Patients wanted help with these issues but many had not discussed them with their opioid prescriber. The biggest problem regarded as a consequence of methadone / buprenorphine was dental difficulties. Surprisingly there were few differences in side effect profiles between either medication, and other than sedation there was no clear dose relationship with any side effects, nor a relationship with the duration of treatment.<br /><br />Since side effects are problematic and can be reduced with appropriate treatment in some cases, and since many patients’ attributions are incorrect, managing side effects should be more frequently addressed in consultations according to Dr Winstock. Fewer side effects may lead to better retention and improved health generally in the drug dependent population.<br /><br />Dr Richard Hallinan then looked at hormonal, sexual and dental problems in methadone maintenance treatment (MMT), starting with some quite early studies. In 1970, over 200 MMT patients retrospectively compared their current complaints with their time before MMT (Bloom and Butcher 1970). 80% on MMT (versus 3% before MMT) complained of weight gain; 40% (versus 15%) of increased use of alcohol; 70% (versus 58%) constipation; 32% (versus 12%) numbness of hands and feet; and 60% (versus 49%) had difficulty with ejaculation.<br /><br />However, a prospective study of 180 men and women before and during MMT (Garbutt and Goldstein, 1972) showed improvements in most physical symptoms during MMT, including aches and pains in muscles, bones and joints, craving, sweating, anorexia and nausea, headaches and insomnia, with little change in constipation, impotence and climax problems.<br /><br />What are addicts like before MMT? Wilczek et al (2002) reported test results on over 100 men and women before they started MMT, finding low haemoglobin (24%), elevated CRP (25%), low testosterone levels (in males, 63%). Imaging methods revealed hepatomegaly in 28% and splenomegaly in 27% with liver steatosis in 15%.<br /><br />Does methadone cause obesity? Szpanowska-Wohn et al (2004) reported statistically significant growth of body weight, in 48 men and women during 9 months of MMT, with fewer underweight and more overweight or obese people. Given the prevalence of overweight and obesity in the general community, it is however not clear whether this is a return to "societal norms" or a direct causal effect.<br /><br />Do people on MMT have sexual dysfunction? Compared with 41 normal controls, Teusch et al 1995 found 37 MMT men and women differed significantly in sexual interest, emotional arousal, physiological arousal, performance and orgasm satisfaction. However as noted above, they may be better or little different from their time on heroin.<br /><br />A number of studies have shown that plasma testosterone is lower in male heroin addicts than controls. Many studies in animals and humans have shown that opioids suppress testosterone, acting at the level of the hypothalamus to reduce secretion of gonadotrophins: "hypogonadotrophic hypogonadism". Amenorrhoea is common in women using heroin, and menstrual cycles tend to normalise during MMT (Schmittner et al 2005).<br /><br />However, studies of men on prescribed opioids have given contradictory results. Only 10% of 92 MMT men reported by Brown et al (2005) had low testosterone, but low mean testosterone was reported in 54 men taking oral sustained-action opioids for chronic pain (Daniell, 2002); and also in 37 men on methadone maintenance (Bliesener et al 1995) while the mean testosterone level of buprenorphine-treated patients did not differ from that of healthy controls. Bliesener et al suggest buprenorphine might be preferred over methadone for this reason. Daniell has called for androgen replacement for men taking opioids who have low testosterone, citing low energy, muscle weakness, sexual dysfunction and higher risk of osteoporosis.<br /><br />Wilczek and Stepan (2003) reported on bone mineral density (BMD) and metabolism before and during MMT, finding that heroin addicts had low average BMD; after one year of MMT, BMD remained unchanged, although osteo-resorption and -formation markers normalised. Recently Kim et al 2006 have reported osteoporosis in 35% and osteopenia in 48% of 92 patients in MMT, with male gender, lower weight and heavy alcohol as risk factors. However this study group may have been at higher risk (eg high rates of HIV medication and the possibility of self-selection in the study recruitment).<br /><br />On the available evidence, screening for osteoporosis probably should be targeted, rather than universal, in men and women on MMT: heavy alcohol smoking, poor diet, history of low stress fractures, and hypogonadism are risk factors to consider.<br /><br />Two studies have reported reduced sperm quality in men on MMT and in heroin addicts: Cicero et al in 1975, but in these studies controls were lacking or poorly matched and alcohol may have been a confounder.<br /><br />Several studies have shown high caries rate and severe periodontal disease in heroin addicts, and excessive intake of food with a high sugar content is common (Scheutz 1995, Zador et al 1996). Although drug addicts often only realized how poor their dental health had become during periods of abstinence (Scheutz, 1995), caries increments were higher among people on methadone maintenance than current heroin abusers, but not statistically significant (Scheutz, 1984).<br /><br />Opioids, like antidepressants, anti-cholinergics and HIV medications, may cause xerostomia (dry mouth) and this is considered a risk factor for dental disease (see Concord Seminar 20 May 2003. Dental problems in addiction treatment subjects: does methadone rot teeth? Can we prevent dental decay? Dr Peter Foltyn).<br /><br />Gingivitis is a reversible inflammatory disease of the periodontal tissues, and periodontitis, in addition, involves destruction of the supporting structures of teeth. Smokers are more susceptible to periodontal diseases, and alcoholics compared with 100 non-addicts exhibited intensive dental caries (Gerlach and Wolters 1977). Poor periodontal health with reduced salivary flow has also been reported in people with chronic HCV, and use of cannabinoids has been associated with increased xerostomia (dry mouth) and severe gingivitis (Fazzi et al 1999).<br /><br />Despite all of these potential confounders to a relationship between opioids (prescribed or illicit) and dental and peridontal disease, a detailed epidemiological study with control for confounders is still lacking. In the meantime, it is reasonable to give the following oral health advice to people on opioid replacement treatment:<br /><br />"Give up smoking. Brush your gums, not just the teeth. Make sure your diet is balanced and avoid excessive high sugar foods. If dry mouth is a problem, try oral lubricants (like 'Oral Balance') especially at night, and dry mouth toothpaste and mouthwash (eg 'Biotene' toothpaste + mouthwash). Avoid alcohol-based mouthwashes, which dry the mouth."<br /><br />Dr Andrew Byrne then spoke on constipation, sweating and prolonged QT in methadone maintenance.<br /><br />Constipation and sweating are common in patients on methadone, probably more commonly at high doses but also at quite low doses such as 30mg daily. The symptoms are usually of a minor nature and require no more than sympathy, explanation and reassurance. Occasionally these may be severe enough to need further attention. If they are ignored, some patients may even drop out of treatment.<br /><br />Constipation can mean different things to different people so clarification is needed about frequency, consistency, bleeding, haemorrhoids, bloating, diet, etc. There is no single approach but we should always address exercise, fluids, diet and consider laxatives or suppositories/enemas if other measures fail. Specialists advise avoiding bowel irritants such as senna and related compounds since these can cause colitis in long-term use. Luminal agents such as Magnesium sulphate, mannitol, lactulose, etc can be used while there are combination products which some patients find acceptable (Movacol, Microlax, Coloxyl with danthron).<br /><br />Sweating likewise can occasionally be so troublesome that patients need help. There may be saturated clothing in the daytime while at night, sheets and pyjamas may need changing due to excessive sweating from methadone. The precise cause is unknown: candidates include hypothalamic and autonomic mechanisms, and histamine release. There may be multiple aetiologies since some get it after the dose, others when in withdrawal and other still at unpredictable times. It may also be seasonal and can respond to reassurance and slight dose reductions.<br /><br />Two medications may be worth trying. The drug loratadine (‘Claratyne’) is an over-the-counter ‘non-drowsy’ antihistamine. A stronger and more specific medication is the anticholinergic drug propantheline (‘Pro-banthine’). The latter may cause dry mouth, dizziness and other autonomic side effects so patients may wish to cut it in two (which needs a pill cutter as the tablet is not scored).<br /><br />Dr Byrne then pointed out that purported methadone related cardiac conduction problems were like a Miss Marple mystery without a body. After 40 years of successful use across the world it would be unlikely that a serious side effect would suddenly be recognised. And, despite the initial report in 2002 by Krantz and colleagues of 17 non-fatal cases on high doses (average 400mg daily), there has still been no series of cases reported in regular maintenance patients.<br /><br />Prolonged QT and ventricular fibrillation remain rare complications of many common medications, often also involving serious concurrent metabolic and structural disturbances. Krantz, who has written about the possible dangers of prolonged QT interval in Lancet, does not recommend ECG in new MMT patients. The NSW Health Department has advised performing a cardiac assessment including electrocardiogram for patients who are being considered for high dose methadone (>200mg daily). This would seem to be a reasonable precaution.<br /><br />In the second half, several case "vignettes" were presented, including three cases of low testosterone in opioid-treated men.<br /><br />Gert, 41 yo, on MMT with a current dose 70 mg, was found on screening to have low total testosterone: 5.5 nmol/L; his testosterone dropped to 3.7 nmol/L despite methadone dose reductions to 55mg. Luteinising hormone (LH) was low. His BMI was 29. Abdominal ultrasound showed fatty liver. His dual energy X-ray densitometry (DEXA) scan showed osteoporosis, with lumbar T-score -2.6.<br /><br />He was seen by an endocrinologist, and on questioning admitted to low energy, low libido, increasing erectile dysfunction, hot flushes, weight gain in last 12 months. Prostate examination and specific antigen (PSA) were normal. He was started on androgen replacement with "Androderm" patches, with resolution of his hot flushes, low energy, low libido, and erectile dysfunction. However patches caused skin irritation, and he much preferred "Sustanon" injections, and later testosterone transdermal gel. At follow up DEXA a year later, lumbar T-score had improved to -1.9.<br /><br />This brief presentation was filled in after questions from the audience: Gert's testicular volumes were normal. Liver function tests, full blood count, thyroid function tests and prolactin were normal. Visual fields were normal (cerebral CT was not done). The main reason for treatment in this case was osteoporosis (not sexual dysfunction, which the patient had not actually complained about). Testosterone assays were performed in the morning, as recommended.<br /><br />We were reminded of the Australian Endocrine Society for androgen replacement treatment: for persistent hypogonadism (at least two morning testosterone levels below 8.0 nmol/L); if there are symptoms of low energy, mood, muscle strength, sexual dysfunction, especially if there is osteopenia, osteoporosis. Prefer testosterone and its esters to synthetic androgens, check the prostate and PSA in men >40yo. Beware the marked placebo effect that often occurs with androgen replacement, which may lead to subsequent disappointment.<br /><br />It was pointed out that haemochromatosis should have been considered in the differential diagnosis (the endocrinologist in this case notes that haemochromatosis and pituitary tumour are the 2 classic exclusions for the diagnosis of hypogonadotrophic hypogonadism. In this case no other clinical features of haemochromatosis were present, but hypogonadism caused by iron deposits in the pituitary can present in isolation from other features of haemochromatosis. Iron studies were normal in this patient).<br /><br />The second case was Ben, a 31 year old labourer from regional NSW, who had been on buprenorphine maintenance the last 2 years, after previous MMT. His alcohol use was very heavy from his late teens, he injected amphetamines from age 21 and heroin from age 23. He was HIV, HBV and HCV seronegative and liver function tests were normal.<br /><br />With his buprenorphine dose 8-12mg daily, he was prescribed sildenafil as he had formed a new relationship and complained of erectile problems. His total testosterone was low at 7.3 nmol/L with low LH, and he was referred to sexual health physician. Penile Doppler was normal, and there was a poor erectile response to a prostaglandin challenge. Follow up testosterone was 8.7 nmol/L. He was advised that his erectile dysfunction was psychogenic.<br /><br />Ben continued to have erectile dysfunction, and resented needing PDE-5 inhibitors. He reduced his buprenorphine dose precipitously, then returned needing dose supplements. Continuing reductions were accompanied by a rise in testosterone in to the high normal range, but erectile dysfunction remained intermittently a problem.<br /><br />A year later his wife blamed buprenorphine for their failure to conceive, insisting he come off treatment, despite by now normal testosterone. Ben was was worried about his sperm count. After counseling, they attended a fertility clinic. Ben's sperm count was normal, his wife's ovarian cyst was removed, and ‘they’ become pregnant 8 weeks later.<br /><br />After reducing his dose to 0.4 mg, Ben came off buprenorphine with protracted symptoms requiring mirtazepine, clonidine, and eventually temazepam. He was off BMT for the birth of his son, but relapsed into heroin use 8 months later.<br /><br />This case illustrated the risk that sexual dysfunction may destabilise opioid replacement treatment; that buprenorphine can be associated with low testosterone and sexual dysfunction; that androgen replacement is not necessarily needed whenever testosterone is low.<br /><br />Bill was a 56 yo man, on MMT continuously since 1991, his current dose 65mg. He had injected heroin since age 22. His current alcohol use was 70-140g/day, and he smoked 10 cigarettes/day. He had chronic back pain after a minor injury in 1999, and fractured his right humerus after slipping in a puddle 2002. He was admitted to hospital with (?aspiration) pneumonia in 2000.<br /><br />Bill had Dupuytrens contractures, spiders, palmar erythema. His blood tests showed elevated GGT and AST, normal ALT, low platelets (130), normal haemoglobin but macrocytosis. He was HCV seropositive and repeatedly HCV-RNA negative.<br /><br />His morning total testosterone was 10.0 nmol/L and 7.2 nmol/L on two occasions (normal 12-36). With his worsening kyphosis, X rays showed wedge fractures of the thoracic spine, and loss of height in lumbar spine. DEXA showed osteoporosis (T score -4.1 spine and -3.0 at hip). Serum folate was low at 3.7 (>7.0).<br /><br />Bill was referred to an endocrinologist, who noted his low BMI (18.8). Coeliac screen, and 25-OH Vitamin D were normal. A repeat total testosterone was 12.1 nmol/L.<br />After dental review, bisphosphonate was prescribed, with calcium supplements and folate.<br /><br />Among the ‘messages’ of this case: the likely importance of alcohol, smoking and dietary factors in the genesis of osteoporosis in this man; the need to check other causes of macrocytosis in an alcoholic; and again, the need not to rush in with androgen replacement.<br /><br />Finally there was a case vignette, to put things in perspective: “I've been on a hundred mils of methadone a day for 25 years and I'm as fit as a fiddle! Most of the people who I started using with are long since dead. I consider methadone has kept me alive, and is the best tonic ever invented.”<br /><br /><br />Summary written by R. Hallinan, A. Winstock and A Byrne.Unknownnoreply@blogger.comtag:blogger.com,1999:blog-2135134153424193830.post-73371902141299762462007-01-31T03:23:00.001+11:002008-11-27T20:16:13.058+11:00Amphetamine/Stimulant Use: Presentations, complications, interventions.Concord Seminar Tuesday 30 January 2007<br /><br />Amphetamine/Stimulant Use: Presentations, complications, interventions.<br /><br />Speakers: Dr Alex Wodak, Director of the Alcohol and Drug Service, and Ms Tarra Adam, Stimulant Treatment Program, Clinical Program Manager, St Vincent’s Hospital, Darlinghurst. Chaired by Dr Bob Batey.<br /><br />Dear Colleagues,<br /><br />Dr Wodak gave an overview of increasing amphetamine use around the world. In 2002, of 91 countries, 56 showed increasing "abuse" of amphetamines, and 11 showed a decrease. There was an increase in amphetamine labs in the years from 1998 to 2004 of 300 to 18,000, with production of Amphetamine Type Substances (ATS) rising from 312 tons to 480 (UNODCCP Global Illicit Drug Trends 2002). Among 15-64 year olds in 2006 there was a prevalence of ATS use in Asia of 0.6%, Oceania of 3%, and Global 0.6% (UNDCP 2006 World Drug Report).<br /><br />Australian Institute of Health and Welfare statistics show an increase in admissions for amphetamine-related psychosis, from approximately 1000 in 1999/2000 to approximately 1600 in 2003/2004. There has probably been a further increase since then, however the increases have been patchy across the country, with increases in NSW and Victoria being less than other states (a large increase in the year 1999 can be attributed to the change from ICD 9 to ICD 10 definitions).<br /><br />Recently there has been a trend away from plant based substances to chemical based drugs due to efforts to avoid both the vagaries of weather, and improved surveillance by air and satellite.<br /><br />To get an idea of the size of the problem in economic terms Dr Wodak pointed out that the size of the illicit "drug industry" in the UK was about the same as British Airways.<br /><br />Regarding the cost effectiveness of treatment, there have not been any studies specifically looking at amphetamines but it is more cost effective to spend money on cocaine drug treatment than on drug law enforcement (Rydell, Everingham. Controlling Cocaine: Supply Versus Demand Programs, RAND, 1994.) Because of similarities to cocaine, these conclusions may be also relevant to amphetamines.<br /><br />In the words of the economist Milton Friedman: "So long as large sums of money are involved - and they are bound to be if drugs are illegal - it is literally hopeless to expect to end the traffic or even to reduce seriously its scope. In drugs, as in other areas, persuasion and example are likely to be far more effective than the use of force to shape others in our image."<br /><br />Dr Wodak described typical presentations of amphetamine use: a psychosis that looks like schizophrenia; severe, even suicidal, depression; aggressive behaviour; strokes, hypertension, and arrhythmias; possibly risky sex including HIV risk; infections from injecting drug use including HCV, septicaemia, bacterial endocarditis; and general "social catastrophes" - financial problems, lost jobs and broken relationships, and gambling problems.<br /><br />No specific regimen has been found to be better or worse than any other for withdrawal management, as amphetamine withdrawal is not well understood.<br /><br />Cochrane reviews have found evidence about the treatment for amphetamine psychosis is limited: medications of interest are conventional antipsychotics, newer antipsychotics and benzodiazepines. An injection of "anti-psychotic drugs can help relieve the symptoms of amphetamine psychosis within an hour, but there is not enough evidence to show what can help after that".<br /><br />Among psychosocial interventions for amphetamine dependence, motivational interviewing and cognitive behavioural therapy show promise. Most in the audience had not used the excellent recommended handbook by Baker, Kay-Lambkin, Lee, Claire and Jenner. “A Brief Cognitive Behavioural Intervention for Regular Amphetamine Users” Department of Health and Ageing 2003 - downloadable from the web: <a href="http://www.health.gov.au/internet/wcms/publishing.nsf/Content/health-pubhlth-publicat-document-cognitive_intervention-cnt.htm/$FILE/cognitive_intervention.pdf">http://www.health.gov.au/internet/wcms/publishing.nsf/Content/health-pubhlth-publicat-document-cognitive_intervention-cnt.htm/$FILE/cognitive_intervention.pdf</a><br />Among non-agonist pharmacological treatments for amphetamine dependence, 30-40 different drugs have been evaluated but none really found to be helpful (see Cochrane Review).<br /><br />Setting the context for agonist pharmacological treatments, Dr Wodak gave the following overview: some amphetamine, especially methamphetamine, users become very chaotic, very volatile, and some become violent. As they may develop paranoia or psychosis, so engaging patients often takes longer, and may be much harder than with other substance dependent patients. They need access to prompt, effective mental health support, and most respond very positively to psychosocial interventions. However a few people with severe intractable use may need Amphetamine Substitution Treatment (AST) in combination with psychosocial interventions.<br /><br />We were pointed to two reviews of the numerous studies of Amphetamine Substitution Treatment (dating from Griffith Edward’s first study in the 1960s, which gave negative results).<br />· Shearer J, Sherman J, Wodak A, van Beek I. Substitution therapy for amphetamine users. Drug and Alcohol Review 2002; 21 (2), 179-185.<br />· Grabowski J, Shearer J, Merrill J, Negus S. Agonist-like replacement pharmacotherapy for stimulant abuse and dependence. Addictive Behaviors. 29 (2004); 1439-1464.<br />These reviews show that, comparable to the situation for methadone in the 1970s, there is reasonable evidence for the effectiveness and safety of AST. It may be not needed for as high a percentage, nor as long, as for heroin dependent people who need methadone.<br /><br />Dr Wodak reminded us of the principles of drug substitution treatment:<br /><br />1. to replace: a short acting drug with a longer action one; an illegal drug with a legal drug; an injectable drug with an oral drug; and<br />2. to stabilise, counsel, and then where ever possible wean off, as in nicotine replacement, and opioid substitution treatment.<br /><br />The NSW Department of Health established Stimulant Treatment Programmes in November 2006 at St Vincent’s Hospital, Darlinghurst and in the Hunter New England region. These programmes offer psychosocial interventions but for severe and refractory cases which meet strict criteria, trials are using immediate release dexamphetamine, as slow release amphetamine (which would be preferable) is not yet licensed for use in Australia. There will be daily supervised dosing of 60mg maximum, only for people with severe intractable problems, with small numbers of about 30 per year in each centre. The programmes are being independently evaluated.<br /><br />The selection criteria are very strict, as Dr Wodak believes it is wiser to start such a treatment with strict limits and later liberalise it if appropriate, rather than "let the genie out of the bottle" too soon.<br /><br />The power of substitution treatment has been shown in Zurich, where there has been saturation treatment with methadone and other opioids (including prescribed heroin), accompanied by a marked decrease in heroin use, drug overdose, crime and heroin seizures by police, and an 82% reduction in new heroin users from 850 in 1990 to only 150 in 2002. (Nordt, Stohler. Lancet 2006 367 1830-34).<br /><br />Another benefit may be if ATS acts like a carrot, getting people with problems to ask for help. A number of people on the waiting list for ATS at St Vincent’s Hospital have improved just with psychosocial interventions while being considered for pharmacotherapy.<br /><br />Tarra Adam then spoke on her work with amphetamine users at Sydney’s St Vincent’s Hospital. She sees those that present at the hospital with problems related to amphetamine use, or who refer themselves.<br /><br />Some present with aggression or violence which is out of character and worries them. Many have learnt to manage their use reasonably well, before seeking any treatment.<br /><br />There is a perception that Alcohol and Drug Services are not for them, and historically these services may have had little to offer. ATS users are often suspicious of the service and whether the service can meet their needs, and may appear to be testing out the therapists, having a strong sense of what they want. Often they wish to be seen in a different area or using a separate entrance, because they are "not like the others".<br /><br />Amphetamine users do tend to show a different profile, being less impoverished and more educated, motivated but hard to engage, often successful at work with a wide range of social contacts, and in better social circumstances than heroin users. Most are daily users, some injecting 3 times a day, some up to 9 times. The majority of people seen at the St Vincent’s Hospital Stimulant Treatment Program are smoking "crystal". Not many switch between amphetamines and cocaine.<br /><br />A range of therapies is offered, including Motivational Interviewing, Cognitive Behavioural Therapy, and people may be referred to a “SMART Recovery” group. However CBT may be just too difficult for a person who is chaotic or paranoid, and often experience cognitive impairment during periods of use or whilst in withdrawal. In the early stages of treatment, some people find it difficult to concentrate and connect with how their thoughts and feelings influence their behaviour. In addition, talking about triggers and motivations to change with stimulant users has in our experience, increased people’s craving for the drug and can contribute to ongoing use and/ or relapse. Therefore we concentrate on addressing the wider impact of stimulant use on their sense of self, the impact of use on their relationships, rather than concentrating on the drug use itself.<br />Therefore, other approaches may be needed, with the aim of trying to engage the person.<br /><br />Narrative Therapy is an example: here the emphasis is centred on people as the experts in their own lives. It views problems as separate from the person and holds that people come with many skills, beliefs, values and abilities that will assist them to reduce the influence of problems such as stimulants in their lives. People often present to therapy with a problem saturated story that dominates beliefs about themselves and influences the choices they make. Narrative conversations seek out the alternative/ preferred stories –stories that are identified by the person about how they would like to live their lives, what it would mean to them to make these changes and supports them to perform this meaning. The therapist seeks out examples of such stories in their lives which support people to break from the influence of the problems they are facing and create new possibilities for their future by increasing awareness of their skills, beliefs, values, and abilities to reduce the influence of stimulants in their lives. A reference for those interested to know more is "What is Narrative Therapy?" by Alice Morgan (can be ordered from the Dulwich Centre - the link for a summary of her book is: <a href="http://www.dulwichcentre.com.au/alicearticle.html">http://www.dulwichcentre.com.au/alicearticle.html</a>)<br /><br />In the second half, chaired by Dr Bob Batey, a range of case vignettes was discussed.<br /><br />The first case was a woman who declared "I always shoot speed on my pension day, Doc. It is the only time I ever clean the house … but now all my veins are gone!"<br /><br />Among the points raised were: possible causes of the exhaustion include following a binge, chronic hepatitis C, and depression. A question was raised about the safety of using antidepressants, including SSRIs, in people who use stimulants, including MDMA. Although this was a theoretical risk, given that these medications and drugs raise monoamine levels in synapses, the expected "epidemic of Serotonin Syndrome has not materialised", as one participant put it. It may be worth suggesting safer ways of administration, as a harm reduction measure, and may be appropriate to refer her for financial management assistance through Centrelink, which offers the Centrepay service for regular payments. It was generally agreed that she was not suitable for AST, given the intermittent nature of her use.<br /><br />In the second case, a man announced "After I use crystal meth I turn into somebody else. I thought I knew how to fly and jumped off the balcony two storeys up to save using the stairs. Now I’m in plaster with two fractured heels and I can’t even get up those stairs".<br /><br />Problems like this occur especially with use of other substances as well, such as benzodiazepines, and often end up in jail, or hospital. Once the person settles they may be able to look at their substance use, especially if they are laid up in hospital. An important question is how worried friends or family can help decrease the risk of harms like this: one response is that health professionals need to help "significant others" who seek help in the first instance by helping them look after themselves.<br /><br />This was also true for the following case, where flatmates sought advice about a young man who had moved in recently from Darlinghurst where "it was too easy to go out every night". He regularly used "ecstasy", took Ritalin for ADD, also selegiline which he read on a web site was good for ADD. He was often up all night, constantly reorganising his room with his things strewn all over the yard. One day he declared angrily "I know you’ve been in my room snooping around. You let things slip that show that you did it. I wish I had video surveillance up there".<br /><br />Tarra Adam said this was a typical presentation to the Alcohol and Drug Service at St. Vincent's Hospital, except that usually the person absolutely believes that others were doing the video surveillance.<br /><br />A comment was that nothing could be taken at face value in this case: neither the ADD diagnosis, the precise substances used, nor any other psychiatric diagnosis.<br /><br />In the next case, a 32 yo man, injecting ATS for 2 years, said: "I'm using ice every day and I can't pull up. Can you give me something to help me detox? Or can I go to a detox somewhere?" Even though the evidence about the amphetamine withdrawal syndrome is limited and there seems to be little benefit from medications, many "detox" facilities will admit amphetamine users. One rehab allows the person to sleep and then clean up, maintaining good hydrations being very important. As many ATS users prefer benzodiazepines to manage their withdrawal, a case could be made in community practice for dispensing a small amount of diazepam to encourage engagement with treatment in future.<br /><br />The final case was a 34 yo man on MMT for 7 years, 11 years injecting, probably 10 years chronic HCV with fluctuating elevated ALT. His methadone dose was 110 mg and his total testosterone was 5.0 -7.2 mmol/L on repeated (morning) testing. He continued to inject ATS several times a week throughout MMT, saying otherwise he has no energy. He was little motivated to change his ATS use.<br /><br />The reasons for this man's lack of energy could include hypogonadism (probably from opioids), chronic hepatitis C, depression, or the effect of amphetamines themselves. Among the approaches could be a trial of methadone reductions or androgen replacement (chronic viral hepatitis is not a contraindication for use of testosterone and its esters, which should be used in preference to synthetic androgens). One could offer antiviral treatment for hepatitis C, which may be a motivation to stop injecting drug use (injecting should not be a contraindication for hepatitis C treatment). a trial of antidepressants may be indicated. These strategies should probably be tried serially rather than simultaneously, to avoid diagnostic confusion in the event of an improvement in energy.<br /><br />Written by Judith Meldrum and Richard Hallinan based on Dr Wodak’s talk.<br /><br /><a href="http://www.redfernclinic.com/">http://www.redfernclinic.com/</a>Unknownnoreply@blogger.comtag:blogger.com,1999:blog-2135134153424193830.post-26208781037417111192006-01-31T03:31:00.001+11:002011-05-23T03:32:46.026+10:00Adam Winstock and Richard Hallinan on driving safety.Dr Adam Winstock, having chaired and presented at a session dedicated to this subject at the recent APSAD conference in November, gave the Concord Dependency Seminar Drugs, Alcohol and Driving on Tuesday 31st January 2006.<br /><br />A whistlestop tour through the epidemiology of self-reported recent substance-affected driving in Australia showed prevalence to range from 3-9%, varying depending on such factors as substance availability, availability of other transport, and the age group and cultural mores. Preferred substances vary greatly, MDMA, cannabis and alcohol being most commonly used by clubbers, and stimulants by truck drivers. Illicit opioids are generally the least commonly used by drivers. Not surprisingly, young men are the group most likely to engage in substance-affected driving. <br /><br />The risk of substance affected driving is not only due to intoxication, but also to more subtle effects such as altered judgement and risk perception, and post-use effects such as the alcohol 'hangover'. Other important factors include the behaviour of passengers (even when the designated driver is not substance affected), driver inexperience, road and vehicle conditions. Such factors tend to aggregate, as in ......a group of drunken teenage males in a rickety car hooning on a dirt road on a dark and stormy night..... <br /><br />The legal concept of the 'culpability' of certain substances was defined: "If drugs contribute to road accidents then drivers found culpable for crashes will be more likely to have drugs in their bodies than drivers deemed non culpable". Culpability is clearly demonstrated with benzodiazepines and alcohol, but not for cannabis, opioids and stimulants.<br /><br />The 'culpability' of alcohol is striking, with a dose-related risk of accidents with rising blood alcohol level (BAL). Permissible blood alcohol concentrations vary from zero (Bulgaria, Turkey), 0.02 = 20 mg/L (Sweden) and 0.08 = 80mg/L (UK, Austria, Spain). Dr Winstock deplored this high permitted level in the UK. <br /><br />Driving under the influence of alcohol is strongly associated with other alcohol related problems, particularly dependence with rate of accidents being 0.5/year for all drivers, 2.5 for binge drinkers and over 3/year for those with alcohol dependence. Further, there is an overrepresentation of alcohol dependent drivers who are caught with very high BAL . <br /><br />Driving simulator studies show impairment of driving skills by cannabis, however there is a wide variation between individuals. The impairment appears to be less in true on-road conditions, possibly because cannabis affected drivers are capable of adapting by driving more carefully. There is some evidence that chronic use of cannabis causes impairment of driving unrelated to current intoxication. <br /><br />Gamma hydroxybutyrate (GHB), like alcohol, produces dose-related psychomotor impairment. It is especially prone to cause gross impairment (including vomiting and amnesia) owing to the narrow 'therapeutic window' of its desired effects. Testing for this drug is difficult as it may be detected in small amounts in the body as a normal metabolic product. We were told that it is used therapeutically in some countries for alcohol withdrawal management. <br /><br />Stimulants such as amphetamines may possibly improve some aspects of driving by increasing vigilance and stamina, and reducing fatigue. However judgement may be impaired at higher doses, with over-confidence, risky or reckless behaviour. Depending on the dose and a person's reaction to the substance, stimulants may have other risks, including altered vision from dilated pupils, the possibility of perceptual disturbance or paranoia. MDMA has been shown to increase the rate of accidents on a driving simulator (De Waard 2002).<br /><br />Given that Attention Deficit Disorder (ADD) is itself a risk for driving accidents, it is an interesting question whether people with this condition ought to be provided with stimulant drugs that might in some cases improve their safety on the road. <br /><br />With prescription medicines, both the underlying condition as well as the effects of the medicine need to be considered, as well as interactions with other substances. An example is opioids, where the stabilised opioid-tolerant person will generally show no signs of psychomotor impairment from their medication. However there may be increased impairment when combined with alcohol or other sedative-hypnotics, and one needs also to consider any associated personality or other psychiatric disorders. <br /><br />In Germany, it was reported, a patient on opioid replacement is considered impaired until proven otherwise and facilities exist for formal testing. In New South Wales, the situation is rather complicated, and Dr Winstock took us step by step through his experience of trying to achieve clarity about legal and professional responsibilities of the health professionals. A useful website for understanding these is www.austroads.com<br /><br />In general it is, in the first instance, a driver's responsibility to report to the relevant Drivers Licensing Authority (DLA) any medical condition which may impair their ability to drive. In NSW, for example, the DLA is the Roads and Traffic Authority. <br /><br />If a patient is "unable to appreciate the impact of their condition, or to take notice of the health professional's recommendations due to cognitive impairment or if driving continues despite appropriate counselling and is likely to endanger the public, the health professional should consider reporting directly to the Driver Licensing Authority" and "in the Australian Capital Territory, New South Wales, Queensland, Tasmania and Victoria ..... health professionals who make such ....without the patients consent but in good faith that a patient is unfit to drive, are protected from civil and criminal liability ". <br /><br />This leaves the health professional with flexibility and at the same time a grey area of legal responsibility. It was pointed out that a family doctor may have very detailed knowledge of a person's psychosocial situation which may help making differentiated judgements but might also involve a conflict between the interests of their patient and society at large. <br /><br />In general situations involving imminent risk and involving commercial drivers call for more decisive action from health professionals.<br /><br />In determining whether to report someone to the Driver Licensing Authority, Dr Winstock advised considering:<br /><br />· the risks associated with disclosure without the individual's consent or knowledge, balanced against the implications of non-disclosure; <br /><br />· whether the circumstances indicate a serious and imminent treat to the health, life or safety of any person.<br /><br /><br />He reminded us of the formula: Risk = (likelihood of the event) x (the severity of consequences).<br /><br />Unfortunately, anomalies do arise. Dr Winstock was advised by a NSW Roads and Traffic Authority spokesperson that a driver need only self-report a medical condition that was chronic, therefore the commencement of methadone treatment need not automatically be notified. However, if a person stayed on methadone treatment for over 12 months, notification would be appropriate. This is exactly the opposite of what an experienced clinician would advise - a patient early in methadone treatment should be advised not to drive until the dose is stabilised, a person stable on methadone maintenance can be expected to be perfectly fit to drive. In cases where illicit use compromises driving safety (regardless of the treatment status of the patient) notification by the patient should be recommended. <br /><br />Dr Winstock's algorithm "What should do we do in practice ?" is based on the need to protect ourselves, the patient and the community where a driver has an impairment to driving. <br /><br />1. Give feedback to the patient on the legal and financial obligations and implications for them, as well as your own legal/professional responsibility. <br /><br />2. Invite the patient to notify the DLA, or inform them of your intention before you do so yourself. <br /><br />3. Document your advice, including that you have told patient what they should do. <br /><br />4. Request feedback and document patient's reported action/inaction re-driving at next appointment. <br /><br />5. Assess immediate risk if patients continue to drive. <br /><br />6. Document and seek second opinion from colleague/DLA. <br /><br />7. Advise patient that unless they notify the DLA you will.<br /><br /><br />The case studies illustrated how these principles might be applied in practice.<br /><br />In the first case, a patient on methadone maintenance developed psychotic depression and was commenced on risperidone and citalopram. The patient was notified to the DLA, and a subsequent medical report was that her akathisia did not affect her psychomotor skills and she was fit to drive. However, another doctor started her on large doses of diazepam for the akathisia. Interest centred on the inappropriateness of using diazepam for akathisia, but also the question of how a doctor best determine whether there was any impairment from this combination of medications. Suggestions included examination 3-4 hours after supervised methadone and diazepam dosing. <br /><br />A second case study dealt with a patient on methadone maintenance known to use benzodiazepines who was observed to stop on the wrong side of the road then reverse across double lines to park on the correct side. He claimed that he did not usually drive as he was unlicensed and his car unregistered. Although the patient showed no signs of benzodiazepine intoxication, the behaviour could reasonably be described as disinhibited, and the responsible doctor chose to deal with this by giving very firm warnings, including a future possible notification of police or the Department of Community Services (responsible for the safety of children in NSW). Debate centred on whether the doctor should have confiscated the car keys, immediately informed the police, notified the DLA (even though it has no powers over unlicensed drivers) and the question of how best to follow up the patient for compliance with acceptable standards.<br /><br />In another case a patient using a cocktail of medications including sedative hypnotics, tricyclic antidepressants, opioids and a major tranquilliser, was offered inpatient management of her problems. She agreed to be admitted but insisted she had first to drive home to cook dinner. In the face of this woman's signs of current intoxication, the doctor acted firmly to take her car keys (which the patient accepted in good spirit), justified by the immediate and serious risk to her and the public. <br /><br />This led to discussion of possible protocols such as requiring anyone entering an alcohol detoxification treatment to agree to notify the DLA of their impairment. It was pointed out that draconian measures by health professionals could push a person out of the therapeutic relationship, losing the opportunity for constructive engagement.<br /><br />Finally, some public health challenges including road side drug testing were discussed: <br /><br />· Legal status of drugs is unrelated to driving risk. <br /><br />· Nor does the mere presence of drugs imply impairment. <br /><br />· Limitations of road side testing, including the number of false negatives <br /><br />· Visible, frequent, random testing may maximise exposure to enforcement and testing may alter perception of risk and lead to a positive impact on people's decision whether to drive.<br /><br /><br />Office tests such as heel-toe, past-pointing, Rombergs and examination for lateral gaze nystagmus are good for alcohol but much less good for other causes of impairment (the latter is a good party trick as well). Dr Winstock briefly described other more sensitive measures of impairment such as head sway measures that may become more widely used in the future.<br /><br />A telling note was struck when Dr Winstock asked how many participants at the seminar routinely asked about driving in every clinical drug and alcohol assessment. At the end of the seminar participants were left with a heightened awareness of this need and a practical framework for acting to protect themselves, the patient and the public. <br /><br />Summary by Richard Hallinan, with contributions from Adam Winstock and Andrew Byrne.Unknownnoreply@blogger.comtag:blogger.com,1999:blog-2135134153424193830.post-73668684344057258772004-04-06T02:32:00.000+10:002009-07-24T02:34:42.382+10:00Cocaine deaths/Take-away doses. 6th April 2004Concord Dependency Seminar. Tues 6th April. Cocaine; take-away doses.<br /><br />Session 1 "At their peril: Cocaine-related deaths in NSW."<br /><br />Prof Shane Darke, National Drug and Alcohol Research Centre<br /><br />Session 2 "Forum on takeaway doses."<br /><br />Prof James Bell, The Langton Centre.<br /><br />Chair Dr Gary Swift<br /><br />Shane Darke spoke on his findings from coroner's records in NSW from 1993 to 2002 of nearly 150 deaths in which cocaine was a cause of death (86%) or a contributing factor. He contrasted the use of cocaine in Australia and America. Ours is very Sydney-based and mostly injected. In the US, cocaine is ubiquitous and it is usually smoked as ‘crack’ or ‘freebase’. He told us that of all sudden deaths in New York, 25% had cocaine in the body. This may make it a contributing factor in some cases, but it may equally be that it reflects the widespread use of cocaine in those dying from other causes.<br /><br />We were told of the different ‘cliques’ of users: snorting, non-dependent ‘middle class’ users to injecting addicts who may swap from one drug to another (speed, coke, heroin, pills, etc). The mixing of drugs and alcohol was the major risk factor in 146 deaths reported from NSW, 96% being poly-drug overdoses. Heroin was the most common accompanying drug (79% as morphine), with alcohol coming second (36%). The medium alcohol level was 0.07%. Others had a variety of other drugs such as cannabis, etc. The actual cause of death appears more complex than with opioids where respiratory depression and hypoxia kill victims, usually within an hour or two. Stimulants are more varied in their effects on the nervous and cardiovascular systems with cardiac and cerebrovascular accidents (stroke) most common reported causes of death.<br />The time of death found weekends over-represented but there was no strong ‘payday peak’ as with heroin deaths. The place of death was a home in 53% of cases with a higher proportion of inner city deaths occurring in hotels. Over a third of all cocaine related deaths in NSW occurred in Kings Cross or Surry Hills postal areas (2010, 2011). Only three deaths occurred outside of Sydney. This does not accord at all with heroin deaths which were much more widespread in suburban Sydney as well as in nearly all rural areas. [It does, however, fit well with a common manner of drug spread early in an epidemic as described by Frischer and others.]<br /><br />Half of the overdose victims in Darke’s study were in paid employment with half of them in professional positions. This is in contrast to heroin deaths which mostly occur in the unskilled and unemployed. Nearly all cocaine deaths occurred in males. The mean age was almost 35 which we were told may reflect an on-going pathogenic process such as arteriosclerosis in some cases or in a lack of resistance as drug users approach middle age.<br /><br />Despite giving some very helpful pointers, Professor Darke said that as a researcher, regarding clinical matters he would defer to his audience. Questions from the large audience centred around just what we as clinicians can do. Education of our patients was the most obvious answer amongst the many other less obvious manoeuvres. Should we advise our own patients to use the Kings Cross injecting room? Should we recommend non-injecting routes of administration? It would seem that basic therapeutic tenets should be strengthened - ‘engagement’ with the drug user, specific drug ‘education‘, sympathetic enquiry into coexisting psychosocial disorders, etc, etc. For those on methadone or other dependency treatment, these need to be optimised in the usual ways and if necessary, a second opinion sought.<br /><br />In the second half of the Concord Seminar, Associate Professor James Bell gave a talk on the issues surrounding take-away provision for methadone and buprenorphine in New South Wales. He discussed the 'anguish' in delicate decisions regarding how we all entrust take-away doses to patients. <br /><br />We were reminded about the clinical methadone audit performed in 2001. Dr Bell said that such information was not likely to be released by the current authorities but that he personally understood that those who provided the data (pharmacists, doctors, nurses, patients, etc) were entitled to expect some feedback on the audit. Some doctors have apparently received critical feed-back, but no averages, ranges or recommended figures have been released. Dr Bell said that one figure from his own research showed 12 month retention rates which were 37% and were the same in private and public sectors.<br /><br />During some discussion with the audience it was agreed that official Guidelines had numerous benefits in dependency practice. (1) They assist doctor say ‘no’ when patients may be unfairly demanding. (2) They save time in preventing undue and lengthy arguments over numbers and timing of such doses, so that, as Dr Bell pointed out, we can spend more time on ‘caring’. (3) They demarcate unambiguous boundaries or limits. (4) They assist busy GPs who may be inexperienced in dependency matters by providing a simple ‘recipe’ for governing take away provisions based on times in treatment, defined stability and in some cases, dose levels (exceptions may be tolerated at 40mg daily or less according to the current methadone take-away guidelines which were promulgated in November 2004).<br /><br />It was agreed by the speaker and the audience that buprenorphine was a safer drug for take-home doses and that the new guidelines should reflect that fact. This was also a finding of the buprenorphine forum held in October 2002.<br /><br />Dr Bell pointed out that to free up places for new patients, there needs to be regular movement of patients from the public to the private sector. Currently, one of the few incentives would seem to be the provision of more take-away doses. It is still not clear if this ‘works’ as many public patients are long term. However, NSW is unique in looking after such folk who are often indigent or homeless, sometimes indefinitely, in the public sector without cost to the individual. One wonders what happens to such folk in other states when money for pharmacies and/or the exigencies of private practice, appointments etc may preclude continued maintenance pharmacotherapy.<br /><br />Andrew Byrne pointed out that most long-term stable patients in the NSW private sector are currently treated perfectly adequately with four take-away doses weekly (eg. Mon, Wed, Fri attendance). Such patients need to clearly document their stability on a regular basis and it is always the prescriber’s responsibility to elicit and record such details. This includes attendance history, work record, family responsibilities, vein condition, urine testing, etc. For experienced doctors, this should involve no anguish, just good clinical acumen and routine practices which most doctors are used to.<br /><br />Finally, it was pointed out that regular buprenorphine take-away doses are currently permitted for certain stable patients in NSW under certain conditions… as well as for emergencies and pregnancy. Despite this, most doctors in the room had not authorised such doses, possibly due to a lack of communication, hence the utility of seminars such as this … and thanks go to Professor Bell for his participation.<br /><br />summaries by Richard Hallinan and Andrew Byrne.<br /><br />contact: 75 Redfern St, Redfern, 2016. (02) 9319 5524Unknownnoreply@blogger.com