Mirtazapine for Methamphetamine Use Disorder: A Randomized Clinical Trial

By
Rebecca McKetin
Steven Shoptaw
Lucy Saunders
Long Nguyen
Philip J. Clare
Gregory J. Dore
Alyna Turner
Olivia M. Dean
Peter J. Kelly
Shalini Arunogiri
Juanita Koeijers
Tayla J. Degan
Louisa Degenhardt
Michael Farrell
David Goodman-Meza
Barbara Sinclair
David Reid
Frank Cordaro
Harry Hill
Robert Lundin
Jeremy Hayllar
Michael Christmass
Willy Liaw
Danica Liu
Amelia Woods
Blaire Brewerton
Ellie Holyoak
Brian Tid-Fung Wu
Hayley Maher
Noni O’Dea
Joel Keygan
Ava Kontogiannis
Lily Palmer
Caity Morrison
Anna Wrobel
Bec Hyland
Gift Kiden
Vanessa Romeo
Khine Wut Yee Kyaw
Marianne Byrne
Samantha Colledge-Frisby
Emma Zahra
Michael Berk
June 1, 2026
0 min

Jama Psychiatry

Overview

A phase 3 randomized clinical trial demonstrated that mirtazapine significantly reduces methamphetamine use in patients with moderate to severe methamphetamine use disorder. The study involved 339 participants and showed a decrease in methamphetamine use days compared to placebo over 12 weeks.

Background

Methamphetamine use disorder poses a significant public health challenge, with millions affected globally and associated risks including psychosis and increased mortality. Currently, no medications are FDA-approved for this disorder, highlighting the need for effective treatment options. Mirtazapine, a tetracyclic antidepressant, has shown promise in earlier trials, warranting further investigation in a broader population.

Data Highlights

Study	Participants	Duration	Findings
Phase 3 Trial	339	12 weeks	Reduced methamphetamine use days compared to placebo

Key Findings

Mirtazapine reduced methamphetamine use days compared to placebo in a phase 3 trial.
Participants reported a median of 24 methamphetamine use days at baseline.
By week 12, there was a mean difference of 2.2 fewer days of methamphetamine use in the mirtazapine group.
Common side effects included drowsiness and weight gain.
Secondary outcomes such as depression and insomnia did not show significant differences.

Clinical Implications

The findings suggest that mirtazapine may be a viable option for reducing methamphetamine use in patients with moderate to severe use disorder. Clinicians should consider this treatment in the context of ongoing psychosocial interventions.

Conclusion

Mirtazapine shows potential as a treatment for methamphetamine use disorder, with evidence supporting its efficacy in reducing use days. Further research may be warranted to explore its role in comprehensive treatment strategies.