EFFECTIVENESS BANK BULLETIN 3 July 2009: reviews and meta-analyses
EFFECTIVENESS BANK BULLETIN 3 July 2009: reviews and meta-analysesThe entries below are our accounts of documents selected by Drug and Alcohol Findings as particularly relevant to improving outcomes from drug or alcohol interventions in the UK. Entries were drafted after consulting related research, study authors and other experts and are © Drug and Alcohol Findings. Permission is given to distribute these entries or incorporate passages in other documents as long as the source is acknowledged including the web address http://findings.org.uk. However, the original documents were not published by Findings; click on the Titles to obtain copies. Free reprints may also be available from the authors; if displayed, click Request reprint to send or adapt the pre-prepared e-mail message. Abstracts are intended to summarise the findings and views expressed in the study. Below are comments from Drug and Alcohol Findings. Links to source documents are in blue. Hover mouse over orange text for explanatory notes.
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NICE-recommended couples therapy endorsed by synthesis of findings ...
Brief alcohol advice in relatively normal primary care reduces drinking ...
Cochrane review confirms methadone maintenance prevents spread of HIV ...
Still no silver-bullet drug to treat stimulant dependence ...
Behavioral couples therapy (BCT) for alcohol and drug use disorders: a meta-analysis.Powers M.B., Vedel E., Emmelkamp P.M.G. Request reprint
Clinical Psychology Review: 2008, 28(6), p. 952–962.
For the minority of patients for whom it feasible, acceptable and safe, this meta-analytic review of behavioural couples therapy suggests it reduces substance use relative to other therapies, and the benefits are more likely to extend to the whole family.
Abstract Behavioural couples therapy assumes that substance use problems and intimate relationships are reciprocally related, such that substance use impairs relationship functioning, and severe relationship distress combined with attempts by partners to control substance use may prompt craving, reinforce substance use, or trigger relapse. To break this vicious circle and transform the relationship in to a positive force, the therapy aims to build support for abstinence and to improve relationship functioning. It features a 'recovery contract' which involves the couple in a daily ritual to reward abstinence, together with techniques for increasing positive activities and improving communication. A requirement for the therapy is that the partner of the problem substance user does not themselves have the same sort of problem.
Descriptive Also known as 'narrative' reviews, these do not attempt to combine findings to create an overall quantitative indicator of the strength of impact of a class or type of intervention. reviews (for example, 1 2) have concluded that behavioural couples therapy produces better outcomes than individual-based treatment for alcoholism and drug abuse problems. However, the strength and consistency of this effect has not been examined because a meta-analysis A study which uses recognised procedures to summarise quantitative results from several studies of the same or similar interventions to arrive at composite outcome scores. Usually undertaken to allow the intervention's effectiveness to be assessed with greater confidence than on the basis of the studies taken individually. of studies of the therapy has not been reported. This meta-analysis combines multiple, well controlled studies to help clarify the overall impact of behavioural couples therapy in the treatment of substance use disorders, and to determine whether this varies across different types of outcomes (such as relationship functioning and substance use) and/or with time after treatment.
A comprehensive search found 12 (eight dealing with drinking problems, four with other substances instead or as well) randomised controlled trials of behavioural couples therapy which could be included in the final analyses, involving altogether 754 couples in intimate relationships. In all but two, couples therapy supplemented other approaches. Eight of the studies compared couples therapy with cognitive-behavioural therapy.
Behavioural couples therapy manuals are available free of charge on request from the web site of the Addiction and Family Research Group. The same site offers a link to a free training program.
Across the studies and amalgamating all outcomes and lengths of follow-up, there was a clear advantage for treatment including behavioural couples therapy versus solely individual-based treatment. At 0.54, the effect size A standard way of expressing the magnitude of a difference (eg, between outcomes in control and experimental groups) applicable to most quantitative data. Enables different measures taken in different studies to be compared or (in meta-analyses) combined. Based on expressing the difference in the average outcomes between control and experimental groups as a proportion of the variability in the outcome across both groups. The most common statistic used to quantify this difference is called Cohen's d. Conventionally this is considered to indicate a small effect when no greater than 0.2, a medium effect when around 0.5, and a large effect when at least 0.8. indicated a medium-size impact. Effects were comparable for alcohol studies and for studies including other drugs, for studies which did or did not combine the therapy with medication, which featured more or less extended versions of the therapy, and (but slightly less strongly) when comparison treatments were limited to cognitive-behavioural therapy without a focus on relationships. Across all the studies, effects were slightly greater for measures of the adverse consequences of substance use and for satisfaction with the relationship (0.52 and 0.57 respectively), than for the frequency of substance use (0.36). However, this pattern varied with time. Immediately after treatment ended, couples therapy was superior to comparison treatments only in respect of satisfaction with the relationship. At later follow-ups, it was superior in respect of all three types of outcomes and to roughly the same medium degree of strength. Possibly substance use outcomes were so good immediately after treatment that it was difficult to improve on them, or perhaps relationship benefits from couples therapy took time to impact on substance use.
When the clients are married or cohabiting couples seeking help for substance dependence problems confined to one of the partners, the authors concluded that behavioural couples therapy results in better outcomes than more typical individual-based treatments. The benefits extend beyond substance use to related problems and the quality of the relationship. Immediate improvements in relationships seem to pave the way for later relative gains in substance use outcomes. Though these outcomes were not included in the analyses, studies have also shown that the therapy outperforms individual-based treatments in respect of child adjustment, cost-effectiveness, and reduced interpersonal violence.
Behavioural couples therapy was one of only
two
The other was contingency management.
psychosocial therapies recommended by Britain's National Institute for Health and Clinical Excellence (NICE) for the treatment of problems related to illicit drug use. In particular, NICE said it should be considered for problem users of stimulants or opioids who are in close contact with a non-drug-misusing partner. Experts reached a similar conclusion after reviewing the alcohol treatment literature for England's National Treatment Agency for Substance Misuse.
Both reviews noted the therapy's limited applicability: the patient must share an intact, live-in relationship with a relative or partner not also experiencing substance use problems, and the relationship must be sufficiently supportive for both to productively engage with the therapy. This will be the case for many (especially male) drinkers, but usually not for long-term dependent users of cocaine or heroin. Care will also be needed to exclude the risk that such therapies, particularly when they engage women in the treatment of male substance users, might perpetuate or aggravate victimisation by abusive partners. Another major limitation is the availability of family therapy of any kind. The dominant paradigm sees addiction as a disorder of the individual and treats it accordingly. Few drug misuse professionals have been trained in family approaches and in the UK there is no appreciable national drive to widen their perspective. The recent emphasis on addressing not just substance use but also other recovery-relevant issues may alter this situation.
The analysis shares the limitations of many meta-analyses. These mean that it is best seen not as an indication of the generalised impact of the therapy, but of how it performed in this set of studies. One assumption underlying the analysis – that the studies were entirely independent of each other – is certainly violated because eight of the 12 involved one or both of the developers of the therapy. Among the remaining four were the three with the least convincing results overall, raising the issue of whether outcomes depend on who is organising the study. Research conducted by teams linked in some way to the intervention they are testing has been found (1 2) to produce more positive findings than fully independent research. In relation to psychosocial therapies for drinking problems, an analysis of relevant studies concluded that therapies were generally equivalent, and that where they were not, the researcher's allegiance to the therapy accounted for However, this analysis restricted itself to drinking outcomes assessed immediately after therapy ended; the featured analysis suggests that the benefits of behavioural couples therapy go beyond drinking itself, and in respect of substance use, emerge only several months later. Nevertheless, allegiance may have played a part in the outcomes of at least eight of the 12 studies. a significant portion of the differences.
What all this means is that it cannot be assumed that fresh applications of the therapy will produce the average advantages over other therapies noted in the featured analysis. Still the analysis offers more support to this therapy than most others can muster, especially since the usual comparator (cognitive-behavioural therapy) was itself a generally effective approach and one relatively hard to better. For the minority of patients for whom it feasible, acceptable and safe, behavioural couples therapy seems a good option relative to other therapies, and one whose benefits are more likely to extend to the whole family.
Last revised 29 June 2009 Comment on this entry Give us your feedback on the site (one-minute survey) Back to contents list at top of page
Cognitive-behavioral treatment with adult alcohol and illicit drug users: a meta-analysis of randomized controlled trials REVIEW ABSTRACT 2009
A randomized trial of individual and couple behavioral alcohol treatment for women STUDY 2009
Aftercare calls suit less relapse-prone patients NUGGET 2005
Dual diagnosis add-on to mental health services improves outcomes NUGGET 2004
Continuing care research: what we have learned and where we are going REVIEW 2009
Initial preference for drinking goal in the treatment of alcohol problems: II. Treatment outcomes STUDY 2010
Antidepressants curb depression but add little to strong 'talking therapies' NUGGET 2006
Still hard to find reasons for matching patients to therapies NUGGET 2008
The effectiveness of brief alcohol interventions in primary care settings: a systematic review.Kaner E.F.S., Dickinson H.O., Beyer F. et al. Request reprint
Drug and Alcohol Review: 2009, 28, p. 301–323.
Combining findings from randomised trials confirmed that brief advice to risky drinking primary care patients can reduce drinking; now the issue is whether in normal practice those benefits will be realised on a grand enough scale to create public health gains.
Abstract The featured report is based on a Cochrane Collaboration systematic review. The account draws on both the featured report and the original review, focusing on general practice rather than the accident and emergency department studies also included in the review. See an earlier Findings analysis for accident and emergency department studies.
Many studies have reported that brief interventions delivered in primary care reduce excessive drinking, but much of this work has been criticised for not being relevant to normal clinical practice. This review aimed to assess the effectiveness of brief interventions in primary care and to determine if outcomes differed between the more tightly controlled 'efficacy' trials, Tests whether an intervention can work under relatively optimal or ideal conditions such as with expert, well trained staff, selected participants, and relatively complete implementation. and the more real-world tests characterised as 'effectiveness' trials. Tests whether an intervention does work under real-world conditions such as with usual staff and training, the usual mix of patients or other participants, and interventions which can feasibly be mounted in normal practice. To find the trials, all relevant electronic databases were searched up to 2006 and reference lists of key articles and reviews were hand-searched. The analysis included randomised controlled trials involving patients in primary care Most of the studies were from general/family practices, but some were conducted in accident and emergency departments. who though not seeking treatment for alcohol problems, received a brief intervention Defined for the purposes of the study as up to five sessions of time-limited engagement with a patient in primary care which involved the provision of information, advice and/or counselling designed to achieve a reduction in alcohol consumption or alcohol-related problems. In practice most trials evaluated a single brief intervention session and typical clinical contact time was around 25 minutes. intended to reduce drinking or alcohol-related problems. Generally, patients had been selected because of screening results or other indications of risky drinking falling short of dependence on alcohol. On average they drank 310g of alcohol a week, nearly 39 UK units, well above safer drinking limits. Most trials compared outcomes for these patients after brief intervention against a control group which was only assessed, treated as usual, and/or provided written information.
The primary meta-analysis A study which uses recognised procedures to summarise quantitative results from several studies of the same or similar interventions to arrive at composite outcome scores. Usually undertaken to allow the intervention's effectiveness to be assessed with greater confidence than on the basis of the studies taken individually. combined alcohol consumption outcomes from 22 trials and over 5800 patients. One year later, patients who had received a brief intervention drank significantly less than controls, amounting on average to an extra 38g of alcohol less a week, nearly five UK units. The analysts established that there was a less than 1 in 20 chance that the real reduction was outside the range from 23g to 54g. However, significant reductions were confined to male patients. All but two trials reported a reduction after brief intervention compared with controls, but estimates varied substantially, indicating that impacts depended on the features of each trial. Extended intervention was associated with a greater reduction in alcohol consumption compared with brief intervention, but the difference was not statistically significant. There was no significant difference in effect sizes A standard way of expressing the magnitude of a difference (eg, between outcomes in control and experimental groups) applicable to most quantitative data. Enables different measures taken in different studies to be compared or (in meta-analyses) combined. Based on expressing the difference in the average outcomes between control and experimental groups as a proportion of the variability in the outcome across both groups. for efficacy and effectiveness trials. Though their results could not be combined, all nine trials which assessed heavy drinking as an outcome found a significant decrease in brief intervention groups relative to control groups.
The authors concluded that brief interventions can reduce alcohol consumption in men, with benefits evident a year after intervention; they are unproven in women, for whom there is insufficient data. Since extended treatment had little extra benefit, primary care intervention for alcohol risk-reduction can be both brief and effective. The studies tended to include patients, clinicians and practices representative of primary care, and there was no significant difference in effectiveness between less and more real-world trials. This suggests that their combined results are applicable to routine clinical practice. Given these findings, the authors recommended that brief interventions should be delivered to hazardous and harmful drinkers in general practices and emergency departments.
The analysis carefully and convincingly showed that in this set of trials, brief intervention led to greater reductions in drinking among risky drinkers than just asking about drinking, or usual clinical care. It differed from other similar analyses in the attempt to answer a crucial question – whether such benefits emerge only in the unrealistic context of a tightly controlled research study with expert, well trained staff, selected participants, and relatively complete implementation, or whether they will survive transplantation to the less controlled context of routine primary care. The verdict that the research would generalise to routine practice rests largely on the finding that impacts in the more real-world trials did not significantly differ from those of the more tightly controlled trials. Certainly an advance in terms of assessing applicability to routine practice, still for several reasons this verdict may be too optimistic. Arguably there remains considerable doubt over whether the average drinking reduction seen in the trials will be replicated if intervention is 'scaled up' to practices in general, and applied by the general run of doctors to the general run of patients.
Prime among these concerns (more on all these issues in the background notes) is that the 'real-worldness' tested by the analysis applied only to the brief intervention phase of the trial. Before this came the selection of sites and of patients at those sites willing to participate in the trial, and the crucial screening process without which the brief interventions could not have targeted appropriate patients, which often supplied data for use in the interventions, and which was typically done by research staff. Putting the whole procedure in to the frame, few if any One of the nine studies could not be obtained and another was available only in full in Spanish. of those categorised as relatively real-world general practice trials can be considered to have been conducted in truly real-world conditions. For example, the most real-world trial recruited only a quarter of the practices it approached (many said they had no time) and just over 1 in 10 contributed data to the analysis. The results cannot be assumed to be representative of what would happen in a normal practice less motivated or less well placed to get involved in, and complete, a brief intervention trial.
Once patients were in the trials, further whittling usually did or may have happened, further reducing confidence in the applicability of the findings to patients overall. Additionally, there was substantial variation between the outcomes of the trials, and, due to the differences between them, the analytic strategy was forced to treat each as having its own characteristic impact rather than one which merely reflected chance variation from the general impact of brief interventions. Given that this was how the findings were generated, it cannot be assumed that any implementation of brief intervention will achieve similar results; each programme will have to demonstrate this for itself.
A related issue is that the studies and the featured analysis started at the point where patients were randomised to a brief intervention. However, the great majority of patients who might benefit never reach this point. In turn this means that even if brief intervention does work, it is unlikely to make the hoped-for health difference at the level of the population as a whole, the public health rationale behind the programmes. The most important reason is that in the studies to date, most practices refuse screening or fail to implement it, and when they do, it is rarely applied to more than a small minority of patients. To a degree this is due to the research context; without this added burden and set of restrictions, more practices would participate and more patients might get screened.
The concerns apply no less to Britain (more in background notes), where the two positive trials demonstrated brief intervention's potential, but not necessarily that it would work in typical practices which themselves identified patients for intervention, and with patients not subject to the multiple selection gateways applied by the studies. Other British studies were either not reflective of primary care or inconclusive about the benefits of intervention, and some have documented the inability or unwillingness of practices to implement widespread systematic screening and intervention.
The degree to which screening and brief intervention are systematically implemented depends on the requirements and incentives applied to primary care practices. Where these are strong, screening can be very widely implemented. Typically, the studies included in the featured report indiscriminately screened all attending adults. An alternative and possibly more feasible model now being implemented in the UK involves targeted/selective screening using AUDIT or shorter screens as part of overall health checks, or when the patient's complaint might be related to or aggravated by heavy drinking (either individually or routinely at clinics dealing with such complaints), and then offering brief advice to risky drinkers. For a low base, Britain is moving towards setting up the systems and training the staff needed to underpin systematic application of these strategies, but in England current plans requiring screening of all new primary care patients will bypass most of the general practice caseload, while Scotland's more robust plans still seem to lack ambition; more in background notes.
Thanks for their comments on this entry in draft to Eileen Kaner of Newcastle University. Commentators bear no responsibility for the text including the interpretations and any remaining errors.
Last revised 21 June 2009 Background notes Comment on this entry Give us your feedback on the site (one-minute survey) Back to contents list at top of page
Universal screening for alcohol problems in primary care fails in Denmark and no longer on UK agenda NUGGET 2008
Controversy over screening primary care patients for risky drinking OFFCUT 2004
Injury rate cut in heavy drinking accident and emergency patients NUGGET 2003
A meta-analysis of motivational interviewing: twenty-five years of empirical studies REVIEW 2010
Investing in alcohol treatment: brief interventions THEMATIC REVIEW 2002
Family doctors' alcohol advice plus follow up cuts long-term medical and social costs NUGGET 2003
Investing in alcohol treatment SERIES OF ARTICLES 2002
Substitution treatment of injecting opioid users for prevention of HIV infection.Gowing L., Farrell M., Bornemann R.
Cochrane Database of Systematic Reviews: 2008, Issue 2, Art. No.: CD004145.
Review conducted for the respected Cochrane collaboration finds that methadone maintenance and allied treatments for opioid dependence consistently and significantly reduce the risk of transmission of blood-borne viruses and curb the spread of HIV.
Abstract Drug injectors are vulnerable to infection with HIV and other blood borne viruses due to the collective use of injecting equipment as well as sexual behaviour. This review aimed to assess the degree to which this risk is affected by oral substitution treatment for opioid dependent injecting drug users by assessing impacts on rates of HIV infection and on behaviours which place people at high risk of viral transmission. Other than those which required participants to recall their past risk behaviour before and after starting treatment, it considered all sorts of studies, not just randomised trials, as long as the outcomes were relevant and participants included current or recently injecting drug users. Non-English language studies were included. The studies were expected largely to relate to methadone, but evidence relating to other oral preparations (buprenorphine, LAAM, codeine and slow release morphine) was also considered.
A comprehensive search strategy discovered 33 studies which could be included in the review, involving about 10,400 participants. Just two were randomised controlled studies; 25 did not include an adequate comparison condition. As a result findings were complicated by influences other than substitution treatment and by potential bias. All but three were solely concerned with methadone treatment, 24 with treatment in a service specialising in addiction treatment, and 25 were set in the USA. Due to differences between the studies, no attempt was made to combine their findings in to an overall quantitative assessment of the impacts of the treatments. Instead the reviewers assessed whether effects were consistent across the studies and across different types of studies.
The studies consistently showed that oral substitution treatment was associated with a significant decrease in the proportion of patients who continued to inject, and in the frequency of injection. These reductions occurred in the first one to three months of treatment and were sustained for at least the first year. However, they were not necessarily sustained after treatment ended, particularly if termination had been involuntary. Treatment was also usually associated with a significant decrease in the sharing of injecting equipment, possibly due to reduced injecting. These benefits were sometimes sustained after treatment ended. In some studies similar reductions in sharing were achieved by other treatment modalities. Overall drug-related risk behaviour assessed by composite scales was significantly reduced. Illicit opioid use (injected or not) also significantly decreased. The data on cocaine use was less consistent; most studies found a significant reduction, but some found no significant difference. Since there were few studies, it was difficult to be conclusive, but the data also suggested reduced sex-related risk of viral transmission, in the form of a lower incidence of multiple partners or exchanges of sex for drugs or money, though condom use was affected little if at all. All four studies which used specially designed surveys to assess overall risk related to drug use or sexual behaviour found significant reductions after entry in to substitution treatment. A different set of four studies assessed relationships between the proportions of people who became HIV positive and their participation in methadone treatment. All found that participation as such, or more extended or continuous participation, was associated with a lower rate of seroconversion.
The reviewers concluded that oral substitution treatment for injecting opioid users reduces drug-related behaviours with a high risk of HIV transmission, but has less effect on sex-related risk behaviours. On this basis, provision of this treatment should be supported in countries with emerging HIV and injecting opioid use problems as well as those with established populations of injecting opioid users. Lack of data from controlled studies limited the strength of the evidence, but these findings supplement stronger review evidence of the effectiveness of substitution treatment in retaining patients and on their drug use. It is currently not possible to say whether these benefits are particular to substitute prescribing, or shared equally with other types of treatment.
Any review is limited by the studies available to it. In this case substantial methodological limitations meant results could not be combined to assess their strength and statistical significance, taking in to account sample sizes and other features of the studies. In particular, the review was unable to offer guidance on how to optimise risk reduction. The consistency of the results is reassuring, but is no substitute for rigorous studies. Nevertheless, the key findings of reduced injecting and probably associated with this, reduced sharing of injecting equipment, is both the intended and logical result of substituting an oral drug for an injected one; it 'makes sense', lending credence to the interpretation that the consistency of the findings reflects a real and consistent impact of making substitute prescribing programmes available.
In fact there are reasons to believe that the findings may be an underestimate of overall benefits across a local population of opioid injectors. Much of the data derives from treatments provided in the previous century, so may underestimate the impacts of improved procedures. Also the review started at the point where injectors enter substitute prescribing programmes, and asked what the impact was on their risk of becoming infected. But there is another major feature of these programmes which might be crucial to risk reduction – their ability to engage large numbers of opioid users in treatment. The risk-reduction benefits identified by the analysis may or may not be greater than those associated with other treatments, but they are likely to be extended to far greater numbers in areas with widely accessible substitute prescribing programmes. Across an entire population of opioid injectors, the result (identified for example in Barcelona) is likely to be reduced HIV-related mortality.
In 2005 the World Health Organization added methadone (and buprenorphine) to its List of Essential Medicines, partly because "The accumulated data demonstrate that methadone maintenance treatment is a major public health tool in ... HIV/AIDS prevention" – the effectiveness issue dealt with in the featured review – but also because it is capable of widespread implementation and the engagement of a large proportion of the at-risk population in treatment. This conclusion was boosted by an analysis for the European Union which found methadone maintenance cost-effectively prolongs and improves the lives of a population of opioid injectors by averting HIV infections, and that the cost of doing so is typically below the cost of treating the infections, creating health service savings. Importantly, the mathematical model used in this analysis showed that as the proportion of local drug users engaged in treatment increases, costs per averted infection dramatically decrease, and benefits across all drug users in or out of treatment escalate. This is because the treatment is capable of removing a large proportion of drug users from networks of injecting equipment sharing, leading to a form of 'herd immunity'. This analysis and others find that benefits in respect of hepatitis C infection are much less convincing, and likely to be substantial at a population level only in very high quality programmes which reduce equipment sharing to very low levels and prevent relapse to injecting drug use.
To a lesser extent, these qualities have a similar influence on HIV prevention, spotlighting the importance of features of the programmes and the regulatory environment within which they operate which can undermine their infection-prevention potential. Among those described for a US think-tank are limited implementation, regulations restricting the import and supply of methadone, restrictions on the types of patients who can enter the programmes (eg, to those who have been failed by other treatments), under-dosing, and counterproductive rules and disciplinary procedures which deter patients and lead to high throw-out rates.
Another benefit not reflected in the analysis is the relatively stable platform substitute prescribing provides for engaging patients in the treatment of HIV or hepatitis C infection and for completing the therapy. By definition this cannot reduce infection among these already infected patients (so its impact will not be reflected in the featured analysis), but it should help prolong their lives and reduce the risk that they will infect others.
Thanks for their comments on this entry in draft to Linda Gowing of the University of Adelaide, Australia and Roy Robertson of Edinburgh University. Commentators bear no responsibility for the text including the interpretations and any remaining errors.
Last revised 25 June 2009 Comment on this entry Give us your feedback on the site (one-minute survey) Back to contents list at top of page
The Drug Treatment Outcomes Research Study (DTORS): final outcomes report STUDY 2009
Opioid substitution therapy in prisons: reviewing the evidence REVIEW 2008
The primary prevention of hepatitis C among injecting drug users REVIEW 2009
International review and UK guidance weigh merits of buprenorphine versus methadone maintenance NUGGET 2008
Opiate antagonist treatment risks overdose NUGGET 2004
Needle and syringe programmes: providing people who inject drugs with injecting equipment REVIEW 2009
The search for medications to treat stimulant dependence.Kampman K.M.
Addiction Science and Clinical Practice: 2008, 4(2), p. 28–35.
Expert and accessible review of the state of play in finding effective and (to the patients) acceptable medications to initiate or sustain abstinence from cocaine or methamphetamine. Though extensive, the results of this US-led search have so far been disappointing.
Abstract Progress in understanding the neurobiology of stimulant dependence has enabled researchers to identify medications whose pharmacological effects suggest they might help patients initiate abstinence or avoid relapse. Several of these medications and a vaccine have shown encouraging results in controlled clinical trials with cocaine-dependent patients, though none has yet been approved in the USA for treating stimulant dependence.
Patients who experience severe cocaine withdrawal symptoms are twice as likely to drop out of treatment and less likely to attain abstinence in outpatient programmes. The most promising medication for initiating abstinence is modafinil, currently approved for the treatment of narcolepsy and itself a mild stimulant. The latest trial involved 210 cocaine-dependent patients who took 200mg or 400mg modafinil daily, or a placebo. Among patients dependent only on cocaine, both dosages of modafinil were superior to placebo for promoting abstinence, but this was not the case among the 41% also dependent on alcohol. Propranolol has also shown promise. For sustaining (as opposed to initiating) abstinence, promising GABAergic medications Cocaine causes euphoria and reinforcement by raising dopamine levels in the mesocortical reward system. One potential way to counterbalance this effect is to elevate mesocortical levels of gamma-aminobutyric acid (GABA), a neurotransmitter that pushes dopamine levels downward by inhibiting the activity of dopaminergic (dopamine-releasing) neurones. Preclinical trials have suggested that GABAergic compounds promote GABA release or conservation. include gamma-vinyl GABA (GVG), tiagabine, and topiramate.
Disulfiram (Antabuse) is a promising cocaine relapse prevention medication with a unique mechanism of action. Its effects lead to extremely high cocaine and dopamine levels when cocaine is ingested, making the high less pleasant by increasing associated anxiety. Four published trials have demonstrated that disulfiram reduces cocaine use in cocaine-dependent patients. Another promising option being explored is the 'vaccine' TA-CD. It works by stimulating the production of cocaine-specific antibodies which bind to cocaine molecules and prevent them crossing the blood–brain barrier.
The search for a medical treatment for methamphetamine dependence started more recently. At least one candidate medication has shown promise in early clinical testing. Bupropion is an antidepressant which supports positive mood by inhibiting the reuptake of dopamine into cells, leaving more of the neurotransmitter circulating in the brain. The same mechanism may be helpful in easing the negative mood symptoms of methamphetamine withdrawal. In a recent trial involving 151 methamphetamine-dependent patients, bupropion recipients (especially those whose methamphetamine use at baseline was less intensive) had somewhat better abstinence outcomes compared with placebo.
Treatment approaches combining efficacious medications and proven behavioural interventions will almost certainly produce the best results. Among the latter is voucher-based reinforcement therapy, a form of contingency management which rewards patients who achieve predetermined therapeutic goals with vouchers redeemable for goods and services.
All the trials to date have been relatively small, so the efficacy and safety of these medications has not been definitively established. Also, most have primarily included men. Although no medications are currently proven to be effective, it is hoped that effective pharmacological treatments for stimulant dependence will soon become available.
Arguably this useful, accessible and well organised review leans towards a 'glass half full' (and soon may be fuller) interpretation of the evidence. As the author acknowledges, stopping stimulant use is much less of a problem (in fact, it occurs naturally even in dependent users) than staying stopped. The bind relapse-prevention medications are in, is that either they are not effective, or if they are, patients will simply stop taking them once they have recovered from the unpleasant consequences of overdoing stimulants to the point where they want to re-experience the highs. Hence the interest in long-acting solutions such as vaccines; the decision to take these can be made at a time when motivation (or coercive pressure) is high, and they remain a restraining influence when motivation wanes. The hope is that this period will embed the habit of non-use. But even these may require the motivation to repeat the procedure once the vaccine wears off. As has been remarked, if the patient has sufficient resolve to keep taking medications, they are probably also well on the way to succeeding in any sort of treatment, whether or not it involves medications. There is also the risk that other drugs not blocked by the vaccine will be substituted for cocaine.
The featured review argues that psychosocial therapies are inadequate due to high drop-out rates, but the same can be said of medication-based programmes. For the reasons given above, few trials have both retained patients in compliance with the medication regimen, and at the same time restrained their stimulant use. Combining medication with rewards for abstinence and/or complying with treatment can help initiate abstinence, but it is unclear whether these gains are typically sustained.
Another recent but more technical overall review of medications for cocaine dependence recently reached similar conclusions. Other recent reviews and meta-analyses A study which uses recognised procedures to summarise quantitative results from several studies of the same or similar interventions to arrive at composite outcome scores. Usually undertaken to allow the intervention's effectiveness to be assessed with greater confidence than on the basis of the studies taken individually. include one of antipsychotic medications in the treatment of cocaine dependence, which found no evidence to support their clinical use. A similar verdict was reached in respect of anticonvulsants and prescribing other stimulants (a variety of substitution treatment).
Prompted by decades of cocaine-dominated drug problems, development of medications to counter these has been a top priority for the US government, which has funded the testing of over 60 marketed medications. Though extensive and persistent, the results of this US-led search have so far been disappointing. However, hopes remain high in some quarters and the search continues. Caution is required because all medications have side-effects, and some of those currently being considered for treating stimulant dependence can have severe consequences. Until risks and costs are clearly balanced by benefits, doctors and patients cannot be advised to consider routine use of any of the candidate medications. In the meantime, European clinicians prefer to rely mostly on psychosocial interventions to reduce cocaine-related problems.
Last revised 10 July 2009 Comment on this entry Give us your feedback on the site (one-minute survey) Back to contents list at top of page
Review of treatment for cocaine dependence STUDY 2010
Traditional medicine in the treatment of drug addiction REVIEW 2009
The state of pharmacotherapy for the treatment of alcohol dependence REVIEW 2009
Take the network into treatment THEMATIC REVIEW 2004
Antabuse reduces cocaine and alcohol use among opiate maintenance patients NUGGET 2001
Pharmacotherapies which work with men do not help women NUGGETTE 2005
Anti-alcohol drug also reduces cocaine use NUGGET 2005
'Real-world' studies show that medications do suppress heavy drinking NUGGET 2005
