Efficacy of Psychostimulant Drugs for Cocaine Dependence
Abstract
Background
Cocaine dependence is an increasingly prevalent disorder for which no medication is approved yet. Likewise opioid for heroin dependence, replacement therapy with psychostimulant could be efficacious for cocaine dependence.
Objectives
To ascertain the efficacy of psychostimulants for cocaine dependence on cocaine use, sustained cocaine abstinence and retention in treatment. The influence of type of drug, comorbid disorders and clinical trial reporting quality over psychostimulants efficacy has also been studied.
Search methods
MEDLINE, EMBASE, PsycINFO, CENTRAL, references of obtained articles and experts in the field.
Selection criteria
Randomized parallel group controlled clinical trials comparing the efficacy of a psychostimulant against placebo have been included.
Data collection and analysis
Two authors evaluated and extracted data. The Relative Risk (RR) was used to assess dichotomous outcomes except for adverse event (AE) induced dropouts for which the risk difference (RD) was preferred. The Standardized Mean Difference (SMD) was used to assess continuous outcomes. To determine the influence of moderating variables, a stratified analysis was conducted. Funnel plots were drawn to investigate the possibility of publication bias.
Main results
Sixteen studies have been included, which have enrolled 1,345 patients. Seven drugs with psychostimulant effect or metabolized to a psychostimulant have been investigated: bupropion, dexamphetamine, methylphenidate, modafinil, mazindol, methamphetamine and selegiline. Psychostimulants did not reduce cocaine use (SMD 0.11, 95%CI: ‐0.07 to 0.29), showed a statistical trend over improving sustained cocaine abstinence (RR 1.41, 95%CI: 0.98 to 2.02, p=0.07) and did not improve retention in treatment (RR 0.97, 95%CI: 0.89 to 1.05). The proportion of AE induced dropouts was similar for psychostimulants and placebo (RD 0.01, 95%CI: ‐0.02 to 0.03). When the type of drug was included as a moderating variable, it was shown that the proportion of patients achieving sustained cocaine abstinence was higher with bupropion and dextroamphetamine, and also with modafinil, at a statistical trend of significance, than with placebo. Nevertheless, no studied drug was efficacious on any of the remaining outcomes. Besides, psychostimulants appeared to increase the proportion of patients achieving sustained cocaine and heroin abstinence amongst methadone maintained dual heroin‐cocaine addicts. The main findings did not seem to be influenced by clinical trial reporting quality. No evidence of publication bias was found.
Authors' conclusions
This review found mixed results, therefore evidence of the efficacy of psychostimulants for cocaine dependence is inconclusive. Nevertheless promising results exist for methadone maintained dual heroin‐cocaine addicts and for some specific drugs such as dexamphetamine and bupropion.
PICOs
Plain language summary
Efficacy of Psychostimulant Drugs for Cocaine Dependence
Cocaine dependence is a frequent disorder for which no medication has clearly proved to be efficacious. Substitution therapy involves the replacement of abused drug, which is often illegal, used several times a day, by a legal, orally administered one. A substitutive drug has similar effects to the abused one, but with a lower addictive potential therefore leading to drug abstinence and involving patients to follow medical and psychological assistance. This strategy has proved to be efficacious for heroin and nicotine dependence. In this review we investigated if psychostimulant substitution was efficacious for cocaine dependence. We found that sixteen studies that had enrolled 1,345 patients investigated the efficacy of psychostimulants against placebo for cocaine dependence. Seven drugs with psychostimulant effect or metabolized to a psychostimulant have been investigated: bupropion, dexamphetamine, methylphenidate, modafinil, mazindol, methamphetamine and selegiline. Psychotherapy was provided in all clinical trials. Study length ranged from 6 to 24 weeks. Psychostimulants did not improve cocaine use, had an unclear beneficial effect over sustained cocaine abstinence and were not associated with higher retention in treatment. Psychostimulants did not increase risk of serious adverse events. It was found that psychostimulants could be efficacious for some groups of patients, such as methadone maintained dual heroin‐cocaine addicts. Therefore, psychostimulants, though have not proved yet their efficacy for cocaine dependence, deserve further investigation.
