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Randomized Controlled Trial
. 2020 Mar 1;77(3):246-255.
doi: 10.1001/jamapsychiatry.2019.3655.

Effects of Mirtazapine for Methamphetamine Use Disorder Among Cisgender Men and Transgender Women Who Have Sex With Men: A Placebo-Controlled Randomized Clinical Trial

Phillip O Coffin  1   2 , Glenn-Milo Santos  1   3 , Jaclyn Hern  1 , Eric Vittinghoff  4 , John E Walker  1 , Tim Matheson  1 , Deirdre Santos  1 , Grant Colfax  1 , Steven L Batki  5
Affiliations
Randomized Controlled Trial

Effects of Mirtazapine for Methamphetamine Use Disorder Among Cisgender Men and Transgender Women Who Have Sex With Men: A Placebo-Controlled Randomized Clinical Trial

Phillip O Coffin et al. JAMA Psychiatry. .

Abstract

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 participants: This 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 measures: Positive 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.

Results: Of 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 relevance: In this expanded replication trial, adding mirtazapine to substance use counseling reduced methamphetamine use and some HIV risk behaviors among cisgender men and transgender women who have sex with men, with benefits extending after treatment despite suboptimal medication adherence.

Trial registration: ClinicalTrials.gov identifier: NCT01888835.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Coffin has led National Institutes of Health–funded studies receiving donated ledipasvir-sofosbuvir from Gilead Sciences (2016-2017) outside the submitted work and has received grant or contract support from the National Institutes of Health, Centers for Disease Control and Prevention, Substance Abuse and Mental Health Services Administration, Agency for Healthcare Research and Quality, and University of California, San Francisco. Dr Santos received grant or contract funds from National Institutes of Health, Centers for Disease Control and Prevention, HIV Prevention Trials Network, and MPact Global Action. Ms Hern has received grant or contract support from the National Institutes of Health and Defense Advanced Research Projects Agency. Dr Vittinghoff has received grant or contract support from National Institutes of Health, Centers for Disease Control and Prevention, Patient-Centered Outcomes in Research Institute, Alzheimer’s Foundation, American Cancer Society, and Buffett Foundation. Mr Walker has received grant or contract support from the National Institutes of Health. Dr Matheson has received grant or contract support from the National Institutes of Health and the Centers for Disease Control and Prevention. Ms Santos reported grants from the National Institute on Drug Abuse during the conduct of the study. Dr Batki has received grant or contract support from the National Institutes of Health, Department of Defense, Department of Veterans Affairs, and University of California San Francisco. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Consolidated Standards of Reporting Trials (CONSORT) Diagram for a Trial of Mirtazapine for Methamphetamine Use Disorder
Figure 2.
Figure 2.. Proportion of Participants With Positive Urine Test Results for Methamphetamine During Follow-up, by Arm
See this image and copyright information in PMC

References

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