Mirtazapine for the treatment of amphetamine and methamphetamine use disorder: A systematic review and meta-analysis

Leen Naji, Brittany Dennis, Tea Rosic, Wojtek Wiercioch, James Paul, Andrew Worster, Lehana Thabane, Zainab Samaan

Research output: Contribution to journalReview articlepeer-review

7 Scopus citations


Background: Amphetamine-type stimulants continue to dominate the global drug markets. Despite this, no pharmacotherapy has been approved for treatment of amphetamine and methamphetamine use disorder (AMD). We evaluate the efficacy of mirtazapine in the treatment of AMD, given emerging evidence that it may alleviate methamphetamine and amphetamine (MA/A) cravings and withdrawals. Methods: We searched five databases from inception until January 28, 2021 for studies with a comparator group evaluating mirtazapine for treatment of AMD. We collected data on reduction in MA/A use, treatment retention, sexual behaviors, depression symptoms, cravings and adverse events. We assessed certainty of evidence using GRADE. Where appropriate, we conducted fixed-effect meta-analyses weighted by inverse variance and calculated the absolute risk reduction. Results: Among the 206 studies screened, we included two parallel-arm placebo-controlled RCTs conducted among cis-gender men and transgender women (n = 180). We found that mirtazapine use likely results in a small reduction of methamphetamine use compared to placebo after 12-weeks (relative risk [RR]=0.81, 95% confidence interval [CI]: 0.63, 1.03; n = 133; moderate certainty evidence due to imprecision). We also found that the use of mirtazapine probably does not improve retention in treatment (RR=1.01, 95% CI: 0.91, 1.12; n = 180; moderate certainty evidence) or depression symptom severity (mean difference [MD]=0.45, 95% CI: −2.88, 3.78; n = 53; moderate certainty evidence). There were no serious adverse events. Conclusions and relevance: Mirtazapine probably results in a small reduction in continued methamphetamine use among cisgender men and transgender women with AMD, but probably does not improve patients’ retention in treatment or depression symptom severity. Study registration: PROSPERO ID: CRD42021236806.

Original languageEnglish (US)
Article number109295
JournalDrug and Alcohol Dependence
StatePublished - Mar 1 2022
Externally publishedYes


  • Amphetamine use disorder
  • GRADE Approach
  • Meta-analysis
  • Methamphetamine use disorder
  • Mirtazapine
  • Stimulant use disorder

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology
  • Psychiatry and Mental health
  • Pharmacology (medical)


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