IMPORTANCE Methamphetamine use is increasingly prevalent and associated with HIV transmission. A previous phase 2a study of mirtazapine demonstrated reductions in methamphetamine use and sexual risk behaviors among men who have sex with men.OBJECTIVE To determine the efficacy of mirtazapine for treatment of methamphetamine use disorder and reduction in HIV risk behaviors. DESIGN, SETTING, AND PARTICIPANTSThis double-blind randomized clinical trial of mirtazapine vs placebo took place from August 2013 to September 2017 in an outpatient research clinic in San Francisco, California. Participants were community-recruited adults who were sexually active; cisgender men, transgender men, and transgender women who (1) had sex with men, (2) had methamphetamine use disorder, and (3) were actively using methamphetamine were eligible. Participants were randomized to receive the study drug or placebo for 24 weeks, with 12 more weeks of follow-up. Data analysis took place from February to June 2018.EXPOSURES Mirtazapine, 30 mg, or matched placebo orally once daily for 24 weeks, with background counseling. MAIN OUTCOMES AND MEASURESPositive urine test results for methamphetamine over 12, 24, and 36 weeks (primary outcomes) and sexual risk behaviors (secondary outcomes). Sleep, methamphetamine craving, dependence severity, and adverse events were assessed. RESULTSOf 241 persons assessed, 120 were enrolled (5 transgender women and 115 cisgender men). The mean (SD) age was 43.3 (9.8) years; 61 (50.8%) were white, 31 (25.8%) were African American, and 15 (12.5%) were Latinx. A mean (SD) of 66% (47%) of visits were completed overall. By week 12, the rate of methamphetamine-positive urine test results significantly declined among participants randomized to mirtazapine vs placebo (risk ratio [RR], 0.67 [95% CI, 0.51-0.87]). Mirtazapine resulted in reductions in positive urine test results at 24 weeks (RR, 0.75 [95% CI, 0.56-1.00]) and 36 weeks (RR, 0.73 [95% CI, 0.57-0.96]) vs placebo. Mean (SD) medication adherence by WisePill dispenser was 38.5% (27.0%) in the mirtazapine group vs 39.5% (26.2%) in the placebo group (P = .77) over 2 to 12 weeks and 28.1% (23.4%) vs 38.5% (27.0%) (P = .59) over 13 to 24 weeks. Changes in sexual risk behaviors were not significantly different by study arm at 12 weeks, but those assigned to receive mirtazapine had fewer sexual partners (RR, 0.52 [95% CI, 0.27-0.97]; P = .04), fewer episodes of condomless anal sex with partners who were serodiscordant (RR, 0.47 [95% CI, 0.23-0.97]; P = .04), and fewer episodes of condomless receptive anal sex with partners who were serodiscordant (RR, 0.37 [95% CI, 0.14-0.93]; P = .04) at week 24. Participants assigned to mirtazapine had net reductions in depressive symptoms (Center for Epidemiologic Studies Depression Scale score, 6.2 [95% CI, 1.3-11.1] points lower; P = .01) and insomnia severity (Athens score, 1.4 [95% CI, 0.1-2.7] points lower; P = .04) at week 24. There were no serious adverse events associated with the study drug. CONCLUSIONS AND RELEVANCEIn this e...

Background Ecological momentary assessments (EMA) are data collection approaches that characterize behaviors in real-time. However, EMA is underutilized in alcohol and substance use research among men who have sex with men (MSM). The aim of this analysis is to explore the correlates of engagement in EMA text messages among substance-using MSM in San Francisco. Methods The present analysis uses data collected from the Project iN pilot study (n=30). Over a two-month period, participants received and responded to EMA daily text messages inquiring about their study medication, alcohol, and methamphetamine use. Baseline characteristics including demographics, alcohol use, and substance use were examined as potential correlates of engagement in EMA text messages in logistic regression and proportional hazards models. Results Participants had a 74% response rate to EMA text messages over the study period. MSM of color had significantly lower adjusted odds of responding to EMA texts 80% of the time or more, compared to white MSM (adjusted odds ratio=0.05, 95%CI=0.01-0.38). College-educated MSM had a lower adjusted hazard of week-long discontinuation in EMA texts (adjusted hazard ratio=0.12, 95%CI=0.02-0.63). Older MSM had a higher adjusted hazard of week-long discontinuation in EMA texts (adjusted hazard ratio=1.15, 95%CI=1.01-1.31). Conclusion Differences in engagement in EMA text prompts were discovered for MSM with different racial/ethnic backgrounds, ages, and education levels. Substance use variables were not correlated with engagement in text messages, suggesting that EMA may be a useful research tool among actively substance-using MSM in San Francisco.

Aims To test aripiprazole for efficacy in decreasing use in methamphetamine-dependent adults, compared to placebo. Design Participants were randomized to receive 12 weeks of aripiprazole or placebo, with a 3 month follow-up and a platform of weekly 30-minute substance abuse counseling. Setting The trial was conducted from January 2009 to March 2012 at the San Francisco Department of Public Health. Participants Ninety actively-using, methamphetamine-dependent, sexually active, adults were recruited from community venues. Measurements The primary outcome was regression estimated reductions in weekly methamphetamine-positive urines. Secondary outcomes were study medication adherence (by self-report and medication event monitoring systems [MEMS]), sexual risk behavior, and abstinence from methamphetamine. Findings Participant mean age was 38.7 years, 87.8% were male, 50.0% white, 18.9% African-American, and 16.7% Latino. Eighty-three percent of follow-up visits and final visits were completed. By intent-to-treat, participants assigned to aripiprazole had similar reductions in methamphetamine-positive urines as participants assigned to placebo (RR 0.88, 95% CI 0.66–1.19, P=0.41). Urine positivity declined from 73%(33/45 participants) to 45%(18/40) in the placebo arm, and from 77% (34/44) to 44% (20/35) in the aripiprazole arm. Adherence by MEMS and self-report was 42% and 74%, respectively, with no significant difference between arms (MEMS P=0.31; self-report P=0.17). Most sexual risk behaviors declined similarly among participants in both arms (all P>0.05). There were no serious adverse events related to study drug, although participants randomized to aripiprazole reported more akathisia, fatigue, and drowsiness (P<0.05). Conclusion Compared with placebo, aripiprazole did not significantly reduce methamphetamine use among actively-using, dependent adults.

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.

Objective To determine whether actively using, methamphetamine (meth)-dependent men who have sex with men (MSM) could be enrolled and retained in a pharmacologic intervention trial, and the degree to which participants would adhere to study procedures, including medication adherence. Study design Phase II randomized, double-blind trial of bupropion vs. placebo. Methods Thirty meth-dependent, sexually active MSM were randomized to receive daily bupropion XL 300 mg or placebo for 12 weeks. Participants received weekly substance use counseling, provided weekly urine specimens, and completed monthly audio-computer assisted self-interview (ACASI) behavioral risk assessments. Adherence was measured by medication event monitoring systems (MEMS) caps (the number of distinct MEMS cap openings divided by the number of expected doses) and self-report. Results Ninety percent completed the trial: 89% of monthly ACASIs were completed, 81% of study visits were attended, and 81% of urine samples were collected. Adherence by MEMS cap was 60% and by self-report was 81% and did not differ significantly by treatment assignment. The median number of positive urine samples was 5.5 out of a possible 11 (50%). Participants in both arms reported similar declines in the median number of sex partners (P = 0.52). No serious adverse events occurred and there were no significant differences in adverse events by treatment assignment (P = 0.11). Conclusions It is feasible to enroll and retain actively using, meth-dependent MSM in a pharmacologic intervention. Bupropion was well tolerated. Study participation and retention rates were high, however, study drug medication adherence was only moderate. Findings support a larger trial with improved adherence support to evaluate the efficacy of bupropion and other pharmacologic interventions for meth dependence in this population.