Efficacy and safety of psychostimulants for amphetamine and methamphetamine use disorders: a systematic review and meta-analysis
BACKGROUND Amphetamine dependence is a public health problem with medical, psychiatric, cognitive, legal and socioeconomic consequences. To date, no pharmacological treatment has been approved for this disorder, and psychotherapy remains the mainstay of treatment. In recent years, psychostimulants have been investigated as a possible replacement therapy. OBJECTIVES To evaluate the efficacy and safety of psychostimulant medications for amphetamine abuse or dependence. The influences of type of drug, type of dependence, comorbid disorders, clinical trial risk of bias and publication of data were also studied. SEARCH METHODS Relevant trials were searched in the following sources: PubMed (January 1966 to 6 June 2012), EMBASE (January 1988 to 6 June 2012), CENTRAL (The Cochrane Library, Issue 5 of 12, May 2012), PsycINFO (January 1985 to 6 June 2012) and the Specialised Register of the Cochrane Drug and Alcohol Group (June 2012). We also searched the reference lists of retrieved trials, the list of studies citing the included trials and the main electronic registers of ongoing trials (ClinicalTrials.gov, International Clinical Trials Registry Platform and EU Clinical Trials Register). Finally, we contacted investigators to request information about unpublished trials. Searches included non-English language literature. SELECTION CRITERIA All randomised, placebo-controlled, parallel-group clinical trials investigating the efficacy or safety of psychostimulants for amphetamine dependence or abuse conducted in an outpatient setting. DATA COLLECTION AND ANALYSIS We used standard methodological procedures expected by The Cochrane Collaboration. MAIN RESULTS Eleven studies were included in the review (791 participants). Studied psychostimulants included dexamphetamine, bupropion, methylphenidate and modafinil. No significant differences were found between psychostimulants and placebo for any of the studied efficacy outcomes. Overall retention in studies was low (50.4%). Psychostimulants did not reduce amphetamine use (mean difference (MD) -0.26, 95% confidence interval (CI) -0.85 to 0.33) or amphetamine craving (MD 0.07, 95% CI -0.44 to 0.59) and did not increase sustained abstinence (relative risk (RR) 1.12, 95% CI 0.84 to 1.49). The proportion of adverse events inducing dropout was similar for psychostimulants and placebo (risk difference (RD) 0.01, 95% CI -0.03 to 0.04). The main findings did not change in any subgroup analysis. AUTHORS' CONCLUSIONS Results of this review do not support the use of psychostimulant medications at the tested doses as a replacement therapy for amphetamine abuse or dependence. Future research could change this conclusion, as the numbers of included studies and participants are limited and information on relevant outcomes, such as efficacy according to the severity of dependence or craving, is still missing.