Literature Collection

Introduction: Drug use related deaths are increasing and the lack of effective treatment for psychostimulants can be largely held responsible. Particularly, no pharmacotherapy is approved for methamphetamine (METH) use disorder despite decades of research. Only psychosocial interventions are clinically used, with limited long-term recovery and relapse.Areas covered: This review aims to select and describe the most relevant findings to date. Selected clinical trials were found in PubMed using the following keywords ('methamphetamine') and ('addiction' OR 'withdrawal' OR 'treatment' OR 'pharmacotherapy'). Randomized placebo-controlled trials enrolling treatment-seeking METH-dependent subjects and inherent secondary analysis were included.Expert opinion: Overall, end-of-treatment abstinence, reduced METH use or lower relapse rates were seen on METH dependent subgroups or attained significance only following post hoc analysis, irrespective of the medication tested. For example, light and heavy METH users seem to respond differently to pharmacotherapy. This together with the heterogeneous nature of the METH dependent population strongly suggests that some drugs herein described (e.g. mirtazapine, methylphenidate) should be further tested in clinical trials focused on subgroups. Lastly, objective measures, such as urinalysis, are mandatory to include in clinical trials and early treatment response and/or medication compliance should be carefully monitored and considered as predictors of success/failure.

BACKGROUND: Currently, there are no accepted FDA-approved pharmacotherapies for cocaine use disorder, though numerous medications have been tested in clinical trials. We conducted a systematic review and meta-analysis to better understand the effectiveness of pharmacotherapy for cocaine use disorder. METHODS: We searched multiple data sources (MEDLINE, PsycINFO, and Cochrane Library) through November 2017 for systematic reviews and randomized controlled trials (RCTs) of pharmacological interventions in adults with cocaine use disorder. When possible, we combined the findings of trials with comparable interventions and outcome measures in random-effects meta-analyses. We assessed the risk of bias of individual trials and the strength of evidence for each outcome using standardized criteria. Outcomes included continuous abstinence (3+ consecutive weeks); cocaine use; harms; and study retention. For relapse prevention studies (participants abstinent at baseline), we examined lapse (first cocaine positive or missing UDS) and relapse (two consecutive cocaine positive or missed UDS'). RESULTS: Sixty-six different drugs or drug combinations were studied in seven systematic reviews and 48 RCTs that met inclusion criteria. Antidepressants were the most widely studied drug class (38 RCTs) but appear to have no effect on cocaine use or treatment retention. Increased abstinence was found with bupropion (2 RCTs: RR 1.63, 95% CI 1.02 to 2.59), topiramate (2 RCTs: RR 2.56, 95% CI 1.39 to 4.73), and psychostimulants (14 RCTs: RR 1.36, 95% CI 1.05 to 1.77), though the strength of evidence for these findings was low. We found moderate strength of evidence that antipsychotics improved treatment retention (8 RCTs: RR 1.33, 95% CI 1.03 to 1.75). DISCUSSION: Most of the pharmacotherapies studied were not effective for treating cocaine use disorder. Bupropion, psychostimulants, and topiramate may improve abstinence, and antipsychotics may improve retention. Contingency management and behavioral interventions along with pharmacotherapy should continue to be explored. SR REGISTRATION: Prospero CRD42018085667.