Dopamine agonists for cocaine dependence.
BACKGROUND
Cocaine is a major drug of abuse. Cocaine dependence is a common and serious condition, which has become nowadays a substantial public health problem. There is a wide and well documented range of consequences associated to chronic use of this drug, such as medical, psychological and social problems, including the spread of infectious diseases (e.g. AIDS, hepatitis and tuberculosis), crime, violence and neonatal drug exposure. Therapeutic management of the cocaine addicts includes an initial period of abstinence from the drug. During this phase the subjects may experience, besides the intense craving for cocaine, symptoms such as depression, fatigue, irritability, anorexia, and sleep disturbances. It was demonstrated that the acute use of cocaine may enhance dopamine transmission and chronically it decreases dopamine concentrations in the brain. Pharmacological treatment that affects dopamine could theoretically reduce these symptoms and contribute to a more successful therapeutic approach.


OBJECTIVE
To evaluate the efficacy and acceptability of dopamine agonists for treating cocaine dependence.


METHODS
We searched: The Cochrane Controlled Trials Register (Cochrane Library, issue 4, 2000), MEDLINE (from 1966 - 2000), EMBASE (from 1980 - 2000), LILACS (from 1982 - 2000), PsycLIT (from 1974 - 2000), Biological Abstracts (1982 to 2000). Reference searching; personal communication; conference abstracts; unpublished trials from pharmaceutical industry; book chapters on treatment of cocaine dependence.


METHODS
The inclusion criteria for all randomised controlled trials were that they should focus on the use of dopamine agonists on the treatment of cocaine dependence. Trials including patients with additional diagnosis such as opiate dependence were also eligible.


METHODS
The reviewers extracted the data independently and Relative Risks, weighted mean difference and number needed to treat were estimated. The reviewers assumed that people who died or dropped out had no improvement and tested the sensitivity of the final results to this assumption.


RESULTS
Twelve studies were included, with 587 participants randomised. Amantadine and Bromocriptine were compared to placebo in most of trials. In two studies amantadine was directly compared to bromocriptine, while amantadine was compared to desipramine, an antidepressant in three. The main efficacy outcome presented was positive urine sample for cocaine metabolites, with no significant differences between interventions. When retention in treatment was assessed as an acceptability measure, it was found a similar rate of patients remaining in treatment in both placebo and active drugs. There were no significant differences in trials where participants had primary cocaine dependence or had additional diagnosis of opioid dependence and/or were in methadone maintenance treatment.


CONCLUSIONS
Current evidence does not support the clinical use of dopamine agonists in the treatment of cocaine dependence. Given the high rate of dropouts in this population, clinicians may consider adding psychotherapeutic supportive measures aiming to keep patients in treatment.
Soares
B G
BG
Centro Cochrane do Brasil, Escola Paulista de Medicina UNIFESP, Av. Dr. Altino Arantes, 1132, São Paulo, SP, Brazil, 96100. bgos@zaz.com.br
Lima
M S
MS
Reisser
A A
AA
Farrell
M
M
D000547:Amantadine / Q000627:therapeutic use; D001971:Bromocriptine / Q000627:therapeutic use; D019970:Cocaine-Related Disorders / Q000188:drug therapy*; D004298:Dopamine / Q000627:therapeutic use*; D006801:Humans; D016032:Randomized Controlled Trials as Topic
D001971:Bromocriptine; D000547:Amantadine; D004298:Dopamine