Mirtazapine Reduces Methamphetamine Use Among Cisgender Men and Transgender Women Who Have Sex With Men

Methamphetamine use disorder is increasing in prevalence in the US, but unfortunately there are no FDA-approved medications for treating it. Mirtazapine, a mixed monoamine agonist-antagonist that increases norepinephrine, serotonin, and dopamine, showed promise in a prior 12-week trial among men who have sex with men. This study was a double-blind, placebo-controlled randomized trial of 24 weeks of mirtazapine (30 mg once daily), or placebo, among 120 cisgender men and transgender women with methamphetamine use disorder who have sex with men.

  • Compared with those receiving placebo, participants receiving mirtazapine had 25% fewer methamphetamine-positive urine samples at 24 weeks, an effect that persisted at 36 weeks (risk ratio, 0.73).
  • 18% of participants receiving mirtazapine and 8% receiving placebo achieved abstinence over the final 2 weeks of treatment, but the difference between groups was non-significant.
  • Adherence to study medication was low; at week 24, participants took 28% of mirtazapine doses and 39% of placebo doses.

Comments: This is the second RCT to demonstrate benefit of mirtazapine in reducing methamphetamine use among cisgender men or transgender women who have sex with men. Many individuals with methamphetamine use disorder have comorbid sleep or mood disorders, and mirtazapine is effective for these indications. Given the dearth of treatment options and the overall safety profile of mirtazapine, it may be reasonable to consider off-label use of mirtazapine in patients with methamphetamine use disorder, especially for those with comorbid sleep disturbance or mood disorder, while we await additional studies in other populations.

Marc R. Larochelle, MD, MPH

Reference: Coffin PO, Santos GM, Hern J, et al. Effects of mirtazapine for methamphetamine use disorder among cisgender men and transgender women who have sex with men: a placebo-controlled randomized clinical trial. JAMA Psychiatry. 2020;77(3):246–255.

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