Context: No approved pharmacologic treatments for methamphetamine dependence exist. Methamphetamine use is associated with high morbidity and is a major cofactor in the human immunodeficiency virus epidemic among men who have sex with men (MSM).
Objective: To determine whether mirtazapine would reduce methamphetamine use among MSM who are actively using methamphetamine.
Design: Double-blind, randomized, controlled, 12-week trial of mirtazapine vs placebo conducted from September 5, 2007, to March 4, 2010.
Setting: San Francisco Department of Public Health.
Participants: Participants were actively using, methamphetamine-dependent, sexually active MSM seen weekly for urine sample collection and substance use counseling.
Interventions: Random assignment to daily oral mirtazapine (30 mg) or placebo; both arms included 30-minute weekly substance use counseling.
Main outcome measures: The primary study outcome was reduction in methamphetamine-positive urine test results. Secondary outcomes were study medication adherence (by self-report and medication event monitoring systems) and sexual risk behavior.
Results: Sixty MSM were randomized, 85% of follow-up visits were completed, and 56 participants (93%) completed the final visit. In the primary intent-to-treat analysis, participants assigned to the mirtazapine group had fewer methamphetamine-positive urine test results compared with participants assigned to the placebo group (relative risk, 0.57; 95% CI, 0.35-0.93, P = .02). Urine positivity decreased from 67% (20 of 30 participants) to 63% (17 of 27) in the placebo arm and from 73% (22 of 30) to 44% (12 of 27) in the mirtazapine arm. The number needed to treat to achieve a negative weekly urine test result was 3.1. Adherence was 48.5% by medication event monitoring systems and 74.7% by self-report; adherence measures were not significantly different between arms (medication event monitoring systems, P = .82; self-report, P = .92). Most sexual risk behaviors decreased significantly more among participants taking mirtazapine compared with those taking placebo (number of male partners with whom methamphetamine was used, P = .009; number of male partners, P = .04; episodes of anal sex with serodiscordant partners, P = .003; episodes of unprotected anal sex with serodiscordant partners, P = .003; episodes of insertive anal sex with serodiscordant partners, P = .001). There were no serious adverse events related to study drug or significant differences in adverse events by arm (P ≥ .99).
Conclusion: The addition of mirtazapine to substance use counseling decreased methamphetamine use among active users and was associated with decreases in sexual risk despite low to moderate medication adherence. Trial Registration clinicalTrials.gov Identifier NCT00497081.