Updated Review of the Treatment of Psychostimulant Dependence for CERGA May 2008

Review of the Evidence

for Clinical Management of Psychostimulant Dependence

CERGA[1] May 2008

1 Aim: To identify reviews of randomised controlled trials (RCTs) of psychostimulant treatment and summarise the findings for CERGA.

2 Methods: Search of the Cochrane database for review articles covering at least the last 10 years. The Cochrane database is a reputable source of systematically reviewed international evidence of RCTs. It uses validated methodology to bring rigour to analyses of evidence in the areas of medical and psychosocial trials to inform work within healthcare systems and academic settings. A Medline-based search from 2007- to May 2008 for new papers supplemented the work available through Cochrane.

The evidence for this review will be re-visited in 3 years, or sooner, if required.

3 Results:

Searching through the Cochrane Database provided reviews covering pharmacological and psychosocial treatments. The Medline-based search identified few other relevant studies from 2007 to May 2008.

Pharmacological management of cocaine misuse:

Four Cochrane systematic reviews found no conclusive evidence of effectiveness in the management of cocaine dependence with medical therapies such as anti-depressants (including tricyclics, monoamine oxidase inhibitors (MAOIs) and selective seratonin reuptake inhibitors (SSRIs)), dopamine agonists (amantadine, bromocriptine and peregolide) and carbamazepine, nor for the use of auricular acupuncture.

A further meta-analysis comparing five stimulant substances (mazindol, dextroamphetamine, methylphenidate, modafinil and bupropion) with placebo[1] concluded that the use of such stimulants as substitution therapy for cocaine dependence did not improve retention in treatment nor cocaine consumption.

Pharmacological management of amphetamine misuse:

One Cochrane Review on the treatment of amphetamine dependence and abuse[2] was identified which included only 4 studies on an SSRI antidepressant (fluoxetine), a calcium channel blocker (amlodipine) and 2 tricyclic antidepressants (imipramine and desipramine). Overall limited benefits were found for the use of these, although fluoxetine significantly reduced cravings and imipramine significantly increased adherence to treatment. The low volume of identified literature weakened the strength of this evidence.

Psychosocial management of psychostimulant misuse:

A large Cochrane Review of a range of psychosocial treatments[3] included 27 RCT studies which had to have assessed reduction of drug use and/or treatment acceptability as one of their main outcomes. The psychosocial treatments covered included:

-  cognitive-behavioural therapy (CBT) including relapse prevention (RP), coping skills training (CST), cognitive therapy (CT), behavioural treatment (BT), community reinforcement approach (CRA), reinforcement-based therapy (RBT), matrix neurobehavioural treatment, and motivationally enhanced group counselling

-  clinical management i.e. non-specific supportive doctor-patient relationship.

-  interpersonal therapy (IPT)

-  supportive-expressive (SE) psychodynamic therapy

-  drug counselling

-  multi-modal/eclectic treatments

(Descriptions of each of these therapies are available in the review)

The two most studied interventions were relapse prevention and contingence reinforcement, followed by drug counselling. Overall significant differences in outcomes were few and where present, effects were modest. However, there was some evidence that CBT approaches were better in some outcomes e.g. reducing drop outs and lowering cocaine use. The most consistently significant improvements in outcome across studies were in those of contingent reinforcement.

Several studies found no differences in outcomes between group or individually delivered interventions; where this was found it was not a consistent effect either way. The number of sessions and length of treatment varied considerably in the 27 studies included. Again results were conflicting and therefore non-conclusive on this point.

To conclude, a number of psychosocial interventions showed some improvements in outcome in the management of cocaine and amphetamine use, but there was no clear pattern of one model of psychosocial treatment being better than others. No evidence was found to support clinical management over CBT approaches, nor professional psychotherapist-delivered therapy over drug counselling. Generally, studies compared treatments between them rather than against no treatment.

Another more recent review of 43 RCTs[4] concludes that psychosocial interventions are moderately effective in reducing psychostimulant use and related harm in dependent individuals. The authors suggest that since the outcomes of behavioural and cognitive approaches are of a similar magnitude, cost-effectiveness should be considered. On this basis briefer interventions would have an advantage over comprehensive interventions. However on several points this review appears to have been incomplete and therefore of limited value.

Non-systematic reports:

The European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) report on cocaine and crack[5] presents the European picture of cocaine prevalence and treatment. The research referred to is not specifically identified, nor reviewed in a systematic way. Promising findings for topiramate and cocaine vaccination are noted but psychosocial interventions are recognised as being the most effective treatment at present.

The RCGP guidelines[6] do not clearly state there is little evidence for pharmacological interventions and indeed give guidance on using some pharmacological interventions. These guidelines are not evidence-based and in light of the above most recent Cochrane Review, findings their relevance and use should be reviewed.

Generalisability of Findings:

One important caveat when considering these reviewed findings is that the bulk of research undertaken has been from the United States, where the demographic profile of cocaine/crack users is quite different from the UK. In the USA crack use in particular is associated with urban deprivation in predominately black and Hispanic communities. How findings translate to the UK context, where the demographic pattern of psychostimulant and cocaine used seems to be very mixed and includes young experimental drug users, professionals and poly-drug users using a mixture of opiates and cocaine is difficult to assess. Crack users in the UK have generally better welfare and health support systems and thus may have improved chances of treatment success[7],[8].

4 Overall Conclusions:

Pharmacological treatment and acupuncture of psychostimulant misuse, in particular cocaine dependence are not justified based on the evidence available, with the possible exception of some antidepressants for amphetamine dependence. This corroborates the National Treatment Agency’s review of research findings in their briefing paper on treating and commissioning services for cocaine/crack.

The evidence for psychosocial interventions is more positive although still very limited. CBT models are the most widely tested (particularly relapse prevention and contingent reinforcement) and have shown modest improvements in selected outcomes, as has drug counselling. However, being in some form of treatment seemed beneficial regardless of the model of care. This tentatively implies it is not necessarily cost-effective to have lots of different, complex interventions available. It again corroborates the NTA summary on commissioning services for crack/cocaine and Orange Book guidance[9], where drug-free interventions such as counselling on a non-residential basis are advised to be the most cost-effective option for psychostimulant misuse.

[1] (Clinical Effectiveness and Reference Group for Addictions)

[1] Castells X et al. (2008) Efficacy of central nervous system stimulant treatment for cocaine dependence: a systematic review and meta-analysis of randomized controlled clinical trials. Addiction 102,1871-1887.

[2] Srisurapanont M, Jarusuraisin N, Kittirattanapaiboon P. Treatment for amphetamine dependence and abuse. Cochrane Database of Systematic Reviews 2001, Issue 4. Art. No.: CD003022. DOI: 10.1002/14651858.CD003022

[3] Knapp WP, Soares B, Farrel M, Lima MS. Psychosocial interventions for cocaine and psychostimulant amphetamines related disorders. Cochrane Database of Systematic Reviews 2007, Issue 3. Art. No.: CD003023. DOI: 10.1002/14651858.CD003023.pub2

[4] Shearer J 2007 Psychosocial approaches to psychostimulant dependence: A systematic review. Journal of Substance Abuse Treatment;32:41-52.

[5] European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) Cocaine and Crack Cocaine: A Growing Public Health Issue.2007, European Union’s Publication Office.

[6] RCGP Guidelines (2004) Ford C. Guidance for working with cocaine and crack users in primary care.

[7] National Treatment Agency briefing papers (2002) Treating cocaine/crack dependence.

[8] National Treatment Agency briefing (2002) Commissioning cocaine/crack treatment.

[9] Department of Health (England) and the devolved administrations (2007). Drug Misuse and Dependence: UK Guidelines on Clinical Management. London: Department of Health (England), the Scottish Government, Welsh Assembly Government and Northern Ireland Executive.