"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.
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