Extended-release naltrexone for methamphetamine dependence among men who have sex with men: a randomized placebo-controlled trial

Background and aims Methamphetamine use is increasingly prevalent and associated with HIV transmission. Early phase human studies suggested naltrexone reduced amphetamine use among dependent individuals. We tested if extended-release naltrexone (XRNTX) reduces methamphetamine use and associated sexual risk behaviors among high-risk methamphetamine-dependent men who have sex with men (MSM). Design Double-blind, placebo-controlled, randomized trial of XRTNX versus placebo over 12 weeks from 2012-2015. Setting San Francisco Department of Public Health, California, USA. Participants 100 community-recruited, sexually-active, actively-using methamphetamine-dependent MSM. Mean age was 43 years, 98% were born male, 55% white, 19% African-American, and 18% Latino. Interventions XRNTX 380mg (N=50) or matched placebo (N=50) administered in 3 gluteal injections at 4-week intervals. Measurements Regression estimated average level and change in level of positive urines over the period 2 -12 weeks (primary outcomes) and sexual risk behaviors (secondary outcome). Findings Ninety percent of visits were completed. By intent-to-treat, participants assigned to XRNTX had similar differences over 2-12 weeks in methamphetamine-positive urines as participants assigned to placebo [IRR 0.95, 95%CI = 0.76 – 1.20; Bayes Factor 0.05). There were no serious adverse events related to study drug, and no differences in frequency of adverse events by treatment arm. Conclusions Notwithstanding very high medication adherence for this study, extended-release naltrexone does not appear to reduce methamphetamine use or sexual risk behaviors among methamphetamine-dependent men who have sex with men compared with placebo.