"The Exit Strategy Part 2: Is there life after methadone?"
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.
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.
Key points:
People come off OST in numerous ways, the most common methods are simply jumping off, and gradual reductions.
The issue of exit from OST 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.
Abstinence from problematic substance use, and psychosocial stability are generally preconditions for coming off OST.
Psychoeducation is important to allay inappropriate fears about coming off treatment.
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”.
A flexible menu of options for coming of treatment should be offered, as well as after care.
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.
Summary:
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.
How should the health professionals respond to a request for reductions toward abstinence? Is there any evidence to guide professional practice?
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.
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.
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%.
Interestingly the 86% figure comes from Andrew Byrne's 9-year follow up published in 2000.
RH proposed some preconditions for sustainably coming off OST. There should be:
• 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);
• no "chemical coping" with life stresses;
• psychosocial stability, including stable mental health (no uncontrolled mood or anxiety disorders) and stable housing; and
• no uncontrolled chronic pain.
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.
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.
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.
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.
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.
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.
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).
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".
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.
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.
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.
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).
The bottom end reductions take most of the time.
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.
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.
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.
Is coming off buprenorphine maintenance any easier?
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).
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!
Nick Lintzeris advised us to take much of what RH had said with a grain of salt!
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.
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).
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).
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.
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.
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.
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.
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.
There were two cases presented:
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.
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.
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.
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.
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.
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.
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.
Selected references
Breen CL, Harris SJ, Lintzeris N, Mattick RP, Hawken L, Bell J, Ritter AJ, Lenné
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.
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.
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.
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.
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."
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.
Kornor H, Waal H. From opioid maintenance to abstinence: a literature review. Drug Alcohol Rev. 2005 May;24(3):267-74.
Lenné M, Lintzeris N, Breen C, Harris S, Hawken L, Mattick R, Ritter A. Withdrawal from methadone maintenance treatment: prognosis and participant
perspectives. Aust N Z J Public Health. 2001 Apr;25(2):121-5.
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.
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.
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]
http://dependencyseminars.blogspot.com/2010_10_01_archive.html
http://www.redfernclinic.com/c/2005/03/peer-support-for-dependency-problems-12_5218.php4
30 November 2011
17 November 2010
Concord 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’.
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.
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.
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.
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).
The DSM diagnosis of pathological gambling (PG) requires five or more of the following:
1. Preoccupation (psychological dependence & salience)
2. Increased amount gambled (tolerance)
3. Irritability/restlessness on cessation (withdrawal)
4. Escape from stress (negative reinforcement & motivation)
5. Chasing losses (erroneous & distorted cognitions)
6. Lying
7. Repeated failure to cease (impaired control)
8. Illegal acts
9. Risked significant relationships
10. ‘Bailout’ (relatives or friends paying gambling debts)
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.
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).
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”.
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.
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.
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.
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).
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.
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).
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.
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.
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.
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.
Self-help groups such as Gamblers Anonymous are effective for a significant minority of people. However, drop-out rates are very high.
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.
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.
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.
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.
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.
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.
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.
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.
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.
The longer you play the more you will lose.
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!
Summary by Richard Hallinan based on Alex Blaszczynski’s presentation and power point.
References:
Blaszczynski A, Walker M, Sharpe L and Nower L. 'Withdrawal and Tolerance Phenomenon in Problem Gambling', International Gambling Studies, 2008. 8 (2), 179-192
Slutske WS, Piasecki TM, Blaszczynski A, Martin NG. Pathological gambling recovery in the absence of abstinence. Addiction. 2010 Dec;105(12):2169-75
Blaszczynski A, Nower L. A pathways model of problem and pathological gambling. Addiction. 2002 May;97(5):487-99
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):179-203
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.
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.
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.
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).
The DSM diagnosis of pathological gambling (PG) requires five or more of the following:
1. Preoccupation (psychological dependence & salience)
2. Increased amount gambled (tolerance)
3. Irritability/restlessness on cessation (withdrawal)
4. Escape from stress (negative reinforcement & motivation)
5. Chasing losses (erroneous & distorted cognitions)
6. Lying
7. Repeated failure to cease (impaired control)
8. Illegal acts
9. Risked significant relationships
10. ‘Bailout’ (relatives or friends paying gambling debts)
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.
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).
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”.
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.
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.
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.
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).
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.
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).
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.
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.
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.
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.
Self-help groups such as Gamblers Anonymous are effective for a significant minority of people. However, drop-out rates are very high.
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.
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.
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.
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.
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.
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.
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.
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.
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.
The longer you play the more you will lose.
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!
Summary by Richard Hallinan based on Alex Blaszczynski’s presentation and power point.
References:
Blaszczynski A, Walker M, Sharpe L and Nower L. 'Withdrawal and Tolerance Phenomenon in Problem Gambling', International Gambling Studies, 2008. 8 (2), 179-192
Slutske WS, Piasecki TM, Blaszczynski A, Martin NG. Pathological gambling recovery in the absence of abstinence. Addiction. 2010 Dec;105(12):2169-75
Blaszczynski A, Nower L. A pathways model of problem and pathological gambling. Addiction. 2002 May;97(5):487-99
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):179-203
10 October 2010
The 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).
Ross Colquhoun described his own extensive experiences with ROD and naltrexone implants.
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
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.
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
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.
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
IF WANTED
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).
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
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.
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%.
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.
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.
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.
Comment RH: one would have to ask whether stable MMT patients are seriously ill.
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
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.
COMMENT RC: IN 10 YEARS THE TGA HAD NEVER QUERIED THE USE OF SAS PROVISIONS TO ENABLE US TO USE NTX IMLPANTS
In the second half of the seminar, two case studies were presented.
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.
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.
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.
This man died of a heroin overdose on 3rd day of MMT induction, having missed 2 days’ dosing.
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.
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:
1. previous failure to achieve abstinence on MMT or BMT and his lack of commitment to opioid abstinence
2. ongoing other drug use
3. impulsivity
4. his being under duress to have the treatment
5. his underlying anxiety disorder.
6. his constant seeking for a quick, preferably chemical, fix to his problems.
7. his previous failure to engage in counseling
This case highlights the need for better lines of communication between providers of opioid pharmacotherapies and the providers of ROD and naltrexone implants.
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.
HIS OUTCOME WAS VERY UNUSUAL IN OUR EXPERIENCE.
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.
Three happy endings:
1. Nelly’s lump went way by 26 months.
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.
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.
A less happy ending:
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.
http://www.dailytelegraph.com.au/news/ex-junkie-wins-6m-but-wont-get-a-cent/story-e6freuy9-1225707964425
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.
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”.
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.
References
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.
Ross Colquhoun described his own extensive experiences with ROD and naltrexone implants.
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
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.
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
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.
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
IF WANTED
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).
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
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.
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%.
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.
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.
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.
Comment RH: one would have to ask whether stable MMT patients are seriously ill.
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
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.
COMMENT RC: IN 10 YEARS THE TGA HAD NEVER QUERIED THE USE OF SAS PROVISIONS TO ENABLE US TO USE NTX IMLPANTS
In the second half of the seminar, two case studies were presented.
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.
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.
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.
This man died of a heroin overdose on 3rd day of MMT induction, having missed 2 days’ dosing.
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.
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:
1. previous failure to achieve abstinence on MMT or BMT and his lack of commitment to opioid abstinence
2. ongoing other drug use
3. impulsivity
4. his being under duress to have the treatment
5. his underlying anxiety disorder.
6. his constant seeking for a quick, preferably chemical, fix to his problems.
7. his previous failure to engage in counseling
This case highlights the need for better lines of communication between providers of opioid pharmacotherapies and the providers of ROD and naltrexone implants.
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.
HIS OUTCOME WAS VERY UNUSUAL IN OUR EXPERIENCE.
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.
Three happy endings:
1. Nelly’s lump went way by 26 months.
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.
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.
A less happy ending:
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.
http://www.dailytelegraph.com.au/news/ex-junkie-wins-6m-but-wont-get-a-cent/story-e6freuy9-1225707964425
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.
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”.
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.
References
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.
26 June 2010
NEW PROGRAM FOR 2010.
Concord Seminar sessions for 2010.
2/02/2010 The Exit Strategy Part 1: Naltrexone Implants: What does the evidence tell us? Ross Colquhoun
20/04/2010 Wet Brain: Alcohol and the Brain - delerium, confabulation, amnesia, and collapse. Prof Paul Haber
8/06/2010 The Other Hepatitis"- An Update on Hepatitis B Part 2 Dr Gail Matthews
Tues 3/08/2010 - Is pathological gambling an addiction? You bet it may or may not be! Prof Alex Blaszczynski
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.
Dr Glenys Dore & Dr Lisa Juckes
30/11/2010 The Exit Strategy Part 2: Is there life after methadone? Prof Nicholas Lintzeris
Organisation:
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.
This seminar series has been set up as a regular activity attracting 2 points/hours for RACGP QA&CPD (activity number 745701)
Objectives and prereading will be circulated prior to each seminar (some details below).
Sponsored by Reckitt Benckiser, manufacturers of buprenorphine products.
THE CONCORD DEPENDENCY SEMINARS 2010 CALENDAR AND PRE-READING:
2/02/2010 - The Exit Strategy Part 1: Naltrexone Implants: What does the evidence tell us?Ross Colquhoun & Richard Hallinan
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.
Pre-reading: http://www.redfernclinic.com/concord/2009/12/concord-seminar-series-tues-1st.php4
20/04/2010 - Wet Brain: Alcohol and the Brain - delirium, confabulation, amnesia, and collapse. Professor Paul Haber.
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.
8/06/2010 - The Other Hepatitis - An Update on Hepatitis B Part 2. Dr Gail Matthews, Infectious Diseases Physician, St Vincent’s Hospital, Darlinghurst
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.
For pre-reading:
http://www.redfernclinic.com/concord/2008/07/other-hepatitis-update-on-hepatitis-b.php4
3/08/2010 - Is pathological gambling an addiction? You bet it may or may not be! Prof Alex Blaszczynski
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. http://www.psych.usyd.edu.au/staff/alexb/
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.
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.
30/11/2010 - The Exit Strategy Part 2: Is there life after methadone? Dr Nick Lintzeris & Richard Hallinan
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.
2/02/2010 The Exit Strategy Part 1: Naltrexone Implants: What does the evidence tell us? Ross Colquhoun
20/04/2010 Wet Brain: Alcohol and the Brain - delerium, confabulation, amnesia, and collapse. Prof Paul Haber
8/06/2010 The Other Hepatitis"- An Update on Hepatitis B Part 2 Dr Gail Matthews
Tues 3/08/2010 - Is pathological gambling an addiction? You bet it may or may not be! Prof Alex Blaszczynski
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.
Dr Glenys Dore & Dr Lisa Juckes
30/11/2010 The Exit Strategy Part 2: Is there life after methadone? Prof Nicholas Lintzeris
Organisation:
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.
This seminar series has been set up as a regular activity attracting 2 points/hours for RACGP QA&CPD (activity number 745701)
Objectives and prereading will be circulated prior to each seminar (some details below).
Sponsored by Reckitt Benckiser, manufacturers of buprenorphine products.
THE CONCORD DEPENDENCY SEMINARS 2010 CALENDAR AND PRE-READING:
2/02/2010 - The Exit Strategy Part 1: Naltrexone Implants: What does the evidence tell us?Ross Colquhoun & Richard Hallinan
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.
Pre-reading: http://www.redfernclinic.com/concord/2009/12/concord-seminar-series-tues-1st.php4
20/04/2010 - Wet Brain: Alcohol and the Brain - delirium, confabulation, amnesia, and collapse. Professor Paul Haber.
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.
8/06/2010 - The Other Hepatitis - An Update on Hepatitis B Part 2. Dr Gail Matthews, Infectious Diseases Physician, St Vincent’s Hospital, Darlinghurst
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.
For pre-reading:
http://www.redfernclinic.com/concord/2008/07/other-hepatitis-update-on-hepatitis-b.php4
3/08/2010 - Is pathological gambling an addiction? You bet it may or may not be! Prof Alex Blaszczynski
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. http://www.psych.usyd.edu.au/staff/alexb/
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.
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.
30/11/2010 - The Exit Strategy Part 2: Is there life after methadone? Dr Nick Lintzeris & Richard Hallinan
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.
20 June 2010
Concord 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.
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?
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.
Learning objectives: at the end of this seminar the participant will be able to:
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.
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.
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
4. show understanding of the association of gambling with financial and interpersonal problems, with crime and depression, and of risk factors for suicide.
5. show understanding of the roles of psychotherapies, pharmacotherapies and harm reduction initiatives in promoting controlled gambling and gambling abstinence.
Pre-reading
International Gambling Studies, Vol. 8, No. 2, 179–192, August 2008
Withdrawal and Tolerance Phenomenon in Problem Gambling
ALEX BLASZCZYNSKI, MICHAEL WALKER, LOUISE SHARPE & LIA NOWER
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.
Addiction. 2002 May;97(5):487-99.
A pathways model of problem and pathological gambling.
Blaszczynski A, Nower L.
At the moment, there is no single conceptual theoretical model of gambling that
adequately accounts for the multiple biological, psychological and ecological
variables contributing to the development of pathological gambling. Advances in
this area are hampered by imprecise definitions of pathological gambling, failure
to distinguish between gambling problems and problem gamblers and a tendency to
assume that pathological gamblers form one, homogeneous population with similar
psychological principles applying equally to all members of the class. The
purpose of this paper is to advance a pathways model that integrates the complex
array of biological, personality, developmental, cognitive, learning theory and
ecological determinants of problem and pathological gambling. It is proposed that
three distinct subgroups of gamblers manifesting impaired control over their
behaviour can be identified. These groups include (a) behaviourally conditioned
problem gamblers, (b) emotionally vulnerable problem gamblers and (c) antisocial,
impulsivist problem gamblers. The implications for clinical management are
discussed.
Suicide Life Threat Behav. 2003 Spring;33(1):88-98.
Pathological gambling and suicidality: an analysis of severity and lethality.
Maccallum F, Blaszczynski A.
Pathological gambling represents a major public health issue. Risk factors for
suicide such as major depression, substance abuse, marital breakdown,
unemployment, financial crises, and legal difficulties are commonly found in
populations of pathological gamblers. The objective of this study was to
systematically investigate the nature of suicidal behavior among
treatment-seeking pathological gamblers and its relationship to gambling
characteristics and depression. Indices of suicidality were assessed in a sample
of 85 treatment-seeking diagnosed pathological gamblers. High rates of suicidal
ideation, suicidal plans, and attempts were found; however, no clear relationship
was observed between suicidality and indices of gambling behavior. Depression
rather than gambling specific characteristics, marital difficulties, or the
presence of illegal behaviors appear to be related to the risk of suicidality.
Aust N Z J Psychiatry. 2002 Jun;36(3):411-5.
Pathological gambling and comorbid substance use.
Maccallum F, Blaszczynski A.
OBJECTIVE: The objective of this study was to determine the rates of substance
use problems in a sample of diagnosed pathological gamblers seeking treatment in
a university teaching hospital cognitive behavioural outpatient clinic. METHODS:
A semistructured interview schedule and the composite international diagnostic
interview (CIDI-auto) were administered to assess substance dependence in a
sample of 75 poker-machine gamblers meeting DSM-IV and South Oaks gambling screen
(SOGS) criteria for pathological gambling. Both the self-reported rates and the
proportion meeting criteria for a psychiatric disorder were determined. RESULTS:
The rates for substance use disorder within a sample of treatment-seeking
pathological gamblers is higher as compared to general population figures. Gender
differences were found with more current alcohol-abuse problems reported among
male than female participants. Non-alcohol-related substance abuse was relatively
lower than rates reported by other studies in the literature. CONCLUSIONS:
Substance abuse is a common comorbid condition of pathological gambling and
therefore should be screened for in routine clinical assessments. Failure to
identify and treat comorbid substance-use disorders in gamblers may lead to
higher relapse rates.
Behav Cogn Psychother. 2009 Jan;37(1):49-59.
Consequences of winning: the role of gambling outcomes in the development of
irrational beliefs.
Monaghan S, Blaszczynski A, Nower L.
BACKGROUND: The development and maintenance of gambling and problem gambling
with its corresponding irrational beliefs may be fundamentally linked to patterns of
wins and losses during electronic gaming machine (EGM) play. METHOD: The current
study investigated the extent to which irrational thoughts and erroneous
perceptions of chance differed based on individual wins or losses. Undergraduate
students (n = 45) completed questionnaires assessing irrational beliefs and
perceptions of chance prior to and following EGM play with credits rather than
money. RESULTS: It was found that players who lost reported a significantly
greater decrease in irrational thoughts and erroneous perceptions of chance and
significantly fewer superstitious beliefs than winning players following play.
CONCLUSIONS: Future studies are needed to further investigate the relationship of
winning to cognitive distortions to guide education and interventions.
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?
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.
Learning objectives: at the end of this seminar the participant will be able to:
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.
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.
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
4. show understanding of the association of gambling with financial and interpersonal problems, with crime and depression, and of risk factors for suicide.
5. show understanding of the roles of psychotherapies, pharmacotherapies and harm reduction initiatives in promoting controlled gambling and gambling abstinence.
Pre-reading
International Gambling Studies, Vol. 8, No. 2, 179–192, August 2008
Withdrawal and Tolerance Phenomenon in Problem Gambling
ALEX BLASZCZYNSKI, MICHAEL WALKER, LOUISE SHARPE & LIA NOWER
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.
Addiction. 2002 May;97(5):487-99.
A pathways model of problem and pathological gambling.
Blaszczynski A, Nower L.
At the moment, there is no single conceptual theoretical model of gambling that
adequately accounts for the multiple biological, psychological and ecological
variables contributing to the development of pathological gambling. Advances in
this area are hampered by imprecise definitions of pathological gambling, failure
to distinguish between gambling problems and problem gamblers and a tendency to
assume that pathological gamblers form one, homogeneous population with similar
psychological principles applying equally to all members of the class. The
purpose of this paper is to advance a pathways model that integrates the complex
array of biological, personality, developmental, cognitive, learning theory and
ecological determinants of problem and pathological gambling. It is proposed that
three distinct subgroups of gamblers manifesting impaired control over their
behaviour can be identified. These groups include (a) behaviourally conditioned
problem gamblers, (b) emotionally vulnerable problem gamblers and (c) antisocial,
impulsivist problem gamblers. The implications for clinical management are
discussed.
Suicide Life Threat Behav. 2003 Spring;33(1):88-98.
Pathological gambling and suicidality: an analysis of severity and lethality.
Maccallum F, Blaszczynski A.
Pathological gambling represents a major public health issue. Risk factors for
suicide such as major depression, substance abuse, marital breakdown,
unemployment, financial crises, and legal difficulties are commonly found in
populations of pathological gamblers. The objective of this study was to
systematically investigate the nature of suicidal behavior among
treatment-seeking pathological gamblers and its relationship to gambling
characteristics and depression. Indices of suicidality were assessed in a sample
of 85 treatment-seeking diagnosed pathological gamblers. High rates of suicidal
ideation, suicidal plans, and attempts were found; however, no clear relationship
was observed between suicidality and indices of gambling behavior. Depression
rather than gambling specific characteristics, marital difficulties, or the
presence of illegal behaviors appear to be related to the risk of suicidality.
Aust N Z J Psychiatry. 2002 Jun;36(3):411-5.
Pathological gambling and comorbid substance use.
Maccallum F, Blaszczynski A.
OBJECTIVE: The objective of this study was to determine the rates of substance
use problems in a sample of diagnosed pathological gamblers seeking treatment in
a university teaching hospital cognitive behavioural outpatient clinic. METHODS:
A semistructured interview schedule and the composite international diagnostic
interview (CIDI-auto) were administered to assess substance dependence in a
sample of 75 poker-machine gamblers meeting DSM-IV and South Oaks gambling screen
(SOGS) criteria for pathological gambling. Both the self-reported rates and the
proportion meeting criteria for a psychiatric disorder were determined. RESULTS:
The rates for substance use disorder within a sample of treatment-seeking
pathological gamblers is higher as compared to general population figures. Gender
differences were found with more current alcohol-abuse problems reported among
male than female participants. Non-alcohol-related substance abuse was relatively
lower than rates reported by other studies in the literature. CONCLUSIONS:
Substance abuse is a common comorbid condition of pathological gambling and
therefore should be screened for in routine clinical assessments. Failure to
identify and treat comorbid substance-use disorders in gamblers may lead to
higher relapse rates.
Behav Cogn Psychother. 2009 Jan;37(1):49-59.
Consequences of winning: the role of gambling outcomes in the development of
irrational beliefs.
Monaghan S, Blaszczynski A, Nower L.
BACKGROUND: The development and maintenance of gambling and problem gambling
with its corresponding irrational beliefs may be fundamentally linked to patterns of
wins and losses during electronic gaming machine (EGM) play. METHOD: The current
study investigated the extent to which irrational thoughts and erroneous
perceptions of chance differed based on individual wins or losses. Undergraduate
students (n = 45) completed questionnaires assessing irrational beliefs and
perceptions of chance prior to and following EGM play with credits rather than
money. RESULTS: It was found that players who lost reported a significantly
greater decrease in irrational thoughts and erroneous perceptions of chance and
significantly fewer superstitious beliefs than winning players following play.
CONCLUSIONS: Future studies are needed to further investigate the relationship of
winning to cognitive distortions to guide education and interventions.
11 May 2010
Prof Paul Haber of alcoholic brain damage. Concord Seminar summary.
Wet Brain: Alcohol and the Brain - delirium, confabulation, amnesia, and collapse.
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.
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.
(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.)
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).
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.
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.
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.)
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.
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).
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.
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.
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).
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
deficiency states.
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 http://www.ncbi.nlm.nih.gov/pubmed/19147798
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.
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)
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.
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.
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.
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.
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.
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.
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.
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.
CASE STUDIES:
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.
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.
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.
Hypotheses for his collapse included alcohol intoxication, sepsis, myocardial infarction, gastrointestinal bleeding, head injury, seizure, other drug use ….
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.
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.
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.
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.
Hypotheses for his inability to walk included cerebellar disease, Wernicke’s and alcohol-and malnutrition-related muscle wasting.
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.
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.
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.
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.
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.
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.
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.
Hypotheses for her mental state included Wernicke’s, alcohol-related cerebrocortical damage, and the effects of continuing diazepam.
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.
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.
Nine weeks after admission, the patient was still awaiting suitable placement.
In each of these cases, Dr Haber suggested thiamine should ideally have been given parenterally in the emergency department, rather than orally.
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. http://dependencyseminars.blogspot.com/
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.
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.
(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.)
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).
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.
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.
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.)
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.
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).
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.
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.
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).
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
deficiency states.
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 http://www.ncbi.nlm.nih.gov/pubmed/19147798
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.
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)
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.
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.
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.
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.
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.
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.
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.
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.
CASE STUDIES:
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.
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.
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.
Hypotheses for his collapse included alcohol intoxication, sepsis, myocardial infarction, gastrointestinal bleeding, head injury, seizure, other drug use ….
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.
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.
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.
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.
Hypotheses for his inability to walk included cerebellar disease, Wernicke’s and alcohol-and malnutrition-related muscle wasting.
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.
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.
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.
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.
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.
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.
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.
Hypotheses for her mental state included Wernicke’s, alcohol-related cerebrocortical damage, and the effects of continuing diazepam.
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.
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.
Nine weeks after admission, the patient was still awaiting suitable placement.
In each of these cases, Dr Haber suggested thiamine should ideally have been given parenterally in the emergency department, rather than orally.
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. http://dependencyseminars.blogspot.com/
5 December 2009
The GREAT debate - what is the best drug for dependency?
Concord Seminar Series – Tues 1st December 2009.
Collegial debate: What is the drug of first choice for opioid dependence?
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.
Richard Hallinan first argued the case for buprenorphine.
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).
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.
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).
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)
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.
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.
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).
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? "
_________________________________________________
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.
Prof Nicholas Lintzeris gave the case for oxycodone based on:
# 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).
# Side effects (there may be less constipation and sweating than with methadone)
# 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).
# 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).
# Stigma (methadone has a stigma which discourages many people from entering maintenance treatments).
# Do-it-yourself injectables clinic.
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.
_____________________________________________________________
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.
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).
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.
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).
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.
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.
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.
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).
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.
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."
____________________________________________________
Andrew Byrne, Redfern Surgery.
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.
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.
However, patients make the choice about which drug much more often than doctors do (see below).
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.
Some references were detailed for the Concord audience.
RCT buprenorphine/methadone.
Ling W, Charuvastra C et al.
Mattick RP, Ali R, White JM et al.
Kristensen O, Espegren O et al.
Kakko J, Grönbladh L, Svanborg KD et al.
Pinto H, Rumball D et al.
Kamien JB, Branstetter SA, Amass L.
Petitjean S, Stohler R, Déglon JJ et al.
Cochrane Database of Systematic Reviews
Reasons for choosing MMT.
Cost (cheapest drug around)
Safe in pregnancy
Available most widely (Aussie pts travel!)
Highest retention rate
Lowest illicit drug use rates
Safety when used under supervision
Original and best known.
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.
English GP study
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.
Pinto H, Rumball D, et al. Journal of Substance Use 2008 13;2:73-82
World’s largest study on OTP.
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
Burns et al. abstract quotes:
“the hazard of leaving treatment was 1.9 times for those on buprenorphine relative to those on methadone”
“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).
Things go better with methadone!
Much lower diversion rates (anecdotally)
No substantial problems with contaminated drug being injected (unlike buprenorphine).
Less “revolving door” syndrome as with buprenorphine (see Burns’ latest study).
Best drug for addiction Rx.
Do you want your patient to have the best chances of getting their lives together, staying in treatment and avoiding illicit drugs?
Of course you do!
Then you should recommend methadone as a first option when there is a choice.
Is this debate “for real”?
Would we be having this debate about antibiotics, antidepressants or hypertension drugs?
Of course not!
**Treatment matching** is the way to go. [Which brings us to the case studies presented in the second half (see below)]
Dependency medicine has a way to go, too!
_______________________________________________________
Post Script
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.
There is no good evidence that naltrexone reduces opioid craving.
Evidence that sexual side effects are lower with buprenorphine is weak, and there is no research for women.
Second daily or thrice weekly buprenorphine dosing in clinical practice seems to suits only a minority.
Naltrexone alone, without bupropion, has small effectiveness for weight loss.
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).
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)
_________________________________________________
Concord Dependency Seminar November 2009, Treatment Matching - Case Studies
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).
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.
What treatment is first choice for Kyle?
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.
_______________________________________________
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.
On examination he is in classic opioid withdrawal, and has plenty of old scars and recent tracks.
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.
What treatment is first choice for Robbie?
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.
_______________________________________________
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.
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.
What treatment is first choice for Emma?
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.
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.
Ref 1.
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; 99:940-5
Collegial debate: What is the drug of first choice for opioid dependence?
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.
Richard Hallinan first argued the case for buprenorphine.
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).
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.
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).
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)
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.
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.
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).
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? "
_________________________________________________
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.
Prof Nicholas Lintzeris gave the case for oxycodone based on:
# 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).
# Side effects (there may be less constipation and sweating than with methadone)
# 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).
# 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).
# Stigma (methadone has a stigma which discourages many people from entering maintenance treatments).
# Do-it-yourself injectables clinic.
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.
_____________________________________________________________
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.
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).
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.
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).
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.
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.
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.
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).
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.
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."
____________________________________________________
Andrew Byrne, Redfern Surgery.
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.
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.
However, patients make the choice about which drug much more often than doctors do (see below).
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.
Some references were detailed for the Concord audience.
RCT buprenorphine/methadone.
Ling W, Charuvastra C et al.
Mattick RP, Ali R, White JM et al.
Kristensen O, Espegren O et al.
Kakko J, Grönbladh L, Svanborg KD et al.
Pinto H, Rumball D et al.
Kamien JB, Branstetter SA, Amass L.
Petitjean S, Stohler R, Déglon JJ et al.
Cochrane Database of Systematic Reviews
Reasons for choosing MMT.
Cost (cheapest drug around)
Safe in pregnancy
Available most widely (Aussie pts travel!)
Highest retention rate
Lowest illicit drug use rates
Safety when used under supervision
Original and best known.
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.
English GP study
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.
Pinto H, Rumball D, et al. Journal of Substance Use 2008 13;2:73-82
World’s largest study on OTP.
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
Burns et al. abstract quotes:
“the hazard of leaving treatment was 1.9 times for those on buprenorphine relative to those on methadone”
“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).
Things go better with methadone!
Much lower diversion rates (anecdotally)
No substantial problems with contaminated drug being injected (unlike buprenorphine).
Less “revolving door” syndrome as with buprenorphine (see Burns’ latest study).
Best drug for addiction Rx.
Do you want your patient to have the best chances of getting their lives together, staying in treatment and avoiding illicit drugs?
Of course you do!
Then you should recommend methadone as a first option when there is a choice.
Is this debate “for real”?
Would we be having this debate about antibiotics, antidepressants or hypertension drugs?
Of course not!
**Treatment matching** is the way to go. [Which brings us to the case studies presented in the second half (see below)]
Dependency medicine has a way to go, too!
_______________________________________________________
Post Script
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.
There is no good evidence that naltrexone reduces opioid craving.
Evidence that sexual side effects are lower with buprenorphine is weak, and there is no research for women.
Second daily or thrice weekly buprenorphine dosing in clinical practice seems to suits only a minority.
Naltrexone alone, without bupropion, has small effectiveness for weight loss.
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).
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)
_________________________________________________
Concord Dependency Seminar November 2009, Treatment Matching - Case Studies
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).
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.
What treatment is first choice for Kyle?
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.
_______________________________________________
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.
On examination he is in classic opioid withdrawal, and has plenty of old scars and recent tracks.
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.
What treatment is first choice for Robbie?
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.
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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.
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.
What treatment is first choice for Emma?
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.
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.
Ref 1.
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; 99:940-5
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