WITHDRAWN: Antidepressants for cocaine dependence.

BACKGROUND: The past decade has witnessed a sustained search for an effective pharmacotherapeutic agent for the treatment of cocaine dependence. While administration of cocaine acutely increases intercellular dopamine, serotonin, and norepinephrine levels by blocking their presynaptic reuptake, chronic cocaine abuse leads to down-regulation of monoamine systems. Post-cocaine use depression and cocaine craving may be linked to this down-regulation. Antidepressant pharmacotherapy, by augmenting monoamine levels, may alleviate cocaine abstinence symptomatology, as well as relieving dysphoria and associated craving by general antidepressant action. OBJECTIVES: To evaluate the efficacy and the acceptability of antidepressants for cocaine dependence SEARCH STRATEGY: We searched Cochrane Drug and Alcohol Group Specialised Register (July 2007), MEDLINE (1966 to July 2007), CINAHL (1982 to July 2007), SCOPUS (July 2007); reference searching; personal communication; conference abstracts; unpublished trials, ongoing trials, relevant web-sites. SELECTION CRITERIA: All randomised controlled trials and controlled clinical trials which focus on the use of any antidepressants for cocaine dependence DATA COLLECTION AND ANALYSIS: The authors independently evaluated the papers, extracted data, rated methodological quality. Doubts were solved throug discussion between all the authors. MAIN RESULTS: 18 studies were included in the review (1177 participants). Positive urine sample for cocaine metabolites was the main efficacy outcome, with no significant results obtained regardless of the type of antidepressant. Compared to other drugs, desipramine performed better but showing just a non significant trend with heterogeneity present as revealed by the chi-square test (8.6, df=3; p=0.04). One single trial showed imipramine performed better than placebo in terms of clinical response according to patient's self-report. A similar rate of patients remaining in treatment was found for both patients taking desipramine or placebo. Results from one single trial suggest fluoxetine patients on SSRIs are less likely to dropout. Similar results were obtained for trials where patients had additional diagnosis of opioid dependence and/or were in methadone maintenance treatment. AUTHORS' CONCLUSIONS: There is no current evidence supporting the clinical use of antidepressants 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.

WITHDRAWN: Dopamine agonists for cocaine dependence.

BACKGROUND: Cocaine dependence is a common and serious condition, which has become a substantial public health problem. There is a wide and well documented range of consequences associated to chronic use of cocaine, such as medical, psychological and social problems.. 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. OBJECTIVES: To evaluate the efficacy and acceptability of dopamine agonists for treating cocaine dependence. SEARCH STRATEGY: Electronic searches of Cochrane Library, EMBASE, MEDLINE, PsycLIT, Biological Abstracts and LILACS; reference searching; personal communication; conference abstracts; unpublished trials from pharmaceutical industry; book chapters on treatment of cocaine dependence, was performed for the primary version of this review in 2001. Another search of the electronic databases was done in December of 2002 for this update. The specialised register of trials of the Cochrane Group on Drugs and Alcohol was searched until February 2003. SELECTION CRITERIA: 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. DATA COLLECTION AND ANALYSIS: 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. MAIN RESULTS: Seventeen studies were included, with 1224 participants randomised. Amantadine, bromocriptine, and pergolide were the drugs evaluated. The main outcomes evaluated were positive urine sample for cocaine metabolites, for efficacy, and retention in treatment, as an acceptability measure. There were no significant differences between interventions, and in trials where participants had primary cocaine dependence or had additional diagnosis of opioid dependence and/or were in methadone maintenance treatment. AUTHORS' 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 other supportive measures aiming to keep patients in treatment.