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Dopamine agonists for the treatment of cocaine dependence

Abstract

Background

Cocaine misuse is a disorder for which no pharmacological treatment of proven efficacy exists. Advances in neurobiology could guide future medication development.

Objectives

To investigate the efficacy and acceptability of dopamine agonists alone or in combination with any psychosocial intervention for the treatment of of people who misuse cocaine.

Search methods

We run the search on 12 January 2015. We searched the Cochrane Drugs and Alcohol Group (CDAG) Specialized Register, PubMed, EMBASE, CINAHL, PsycINFO, ICTRP, clinicaltrials.gov and screened reference lists.

Selection criteria

Randomised controlled trials (RCTs) and controlled clinical trials (CCTs) comparing dopamine agonists alone or associated with psychosocial intervention with placebo, no treatment or other pharmacological interventions.

Data collection and analysis

We used standard Cochrane methodological procedures.

Main results

Twenty four studies, including 2147 participants, met the inclusion criteria. Comparing any dopamine agonist versus placebo, we found no differences for any of the outcomes considered: dropout (moderate quality of evidence), abstinence (low quality of evidence), severity of dependence (low quality of evidence), adverse events (moderate quality of evidence). This was also observed when single dopamine agonists were compared against placebo. Comparing amantadine versus antidepressants, we found low quality of evidence that antidepressants performed better for abstinence (RR 0.25, 95% CI 0.12 to 0.53) based on two studies with 44 participants. No differences were found for dropout or adverse events, for both moderate quality of evidence.

The major flaws of the included studies concerned selection bias because most studies did not report information about sequence generation (80%) and allocation concealment methods (86%): half of the included studies were judged at unclear risk of performance bias and 62.5% at unclear risk of detection bias for what concerns subjective outcomes.

Authors’ conclusions

Current evidence from RCTs does not support the use of dopamine agonists for treating cocaine misuse. This absence of evidence may leave to clinicians the alternative of balancing the possible benefits against the potential adverse effects of the treatment. Even the potential benefit of combining a dopamine agonist with a more potent psychosocial intervention, which was suggested by the previous Cochrane Review (Soares 2003), is not supported by the results of this Cochrane Review update.

Plain language summary

Dopamine agonists for the treatment of people who misuse cocaine

Background

A pharmacological agent with proven efficacy does not exist for treatment of cocaine misuse. Cocaine is an alkaloid derived from the erythroxylon coca leaf that is used as powder for intranasal or intravenous use or as crack, a free-base form which is smoked. Cocaine misuse is a major public health problem because its use can be associated with medical and psychosocial complications including the spread of infectious diseases (such as AIDS, hepatitis and tuberculosis), crime, violence and neonatal drug exposure. In this Cochrane Review we looked at the evidence on the efficacy and acceptability of dopamine agonists as a treatment, used either alone or in combination with any psychosocial intervention, for people addicted to cocaine.

Study characteristics

We searched scientific databases and internet resources to identify randomised controlled trials (where participants are allocated at random to any dopamine agonist drug or placebo or another type of drug aimed to reduce use of cocaine. We also assessed dropout from treatment and frequency of side effects. We included adults of any gender, age or ethnicity.

Key results

We included 24 studies with 2147 participants, who were all addicted to cocaine. Most were men (82.%)with an average age of 37 years. The mean duration of the included trials was seven weeks (range 1.5 to 16 weeks) Twenty-two studies were conducted in USA, one in Brazil and one in Spain; all but four were outpatients.

The included trials studied the following drugs: amantadine, bromocriptine, L dopa/Carbidopa, pergolide, cabergoline hydergine, and pramipexole. All compared dopamine agonist versus placebo. Four studies compared amantidine versus antidepressants.

No differences were found between the drugs and placebo for any of the outcomes considered: dropout (moderate quality of evidence), abstinence (low quality of evidence), severity of dependence (low quality of evidence), adverse events (moderate quality of evidence). Antidepressants was found to be better than the dopamine agonist amantidine for abstinence, but this was based on two studies with very few participants and low quality of evidence. There is no current evidence supporting the clinical use of dopamine agonist medications in the treatment of cocaine misuse. The evidence is current to 12 January 2015.

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