ResearchPod Summary
Methamphetamine use disorder is a major public health crisis with no universally approved pharmacological treatments. While previous small-scale, phase 2 trials suggested that mirtazapine—a common tetracyclic antidepressant—might help reduce stimulant use by modulating serotonin and dopamine pathways, its effectiveness in real-world clinical settings remained unproven. This study aimed to fill that gap by testing the drug across a diverse group of patients in standard outpatient substance use clinics.
Researchers conducted a multi-site, double-blind, placebo-controlled, phase 3 randomized clinical trial in Australia. They recruited 344 adults with moderate to severe methamphetamine use disorder. Participants were randomized to receive either 30 mg of mirtazapine daily or an equivalent placebo for 12 weeks. The primary measure of success was the reduction in the number of days the participants used methamphetamine in the 28-day period leading up to the 12-week mark, as recorded by the Timeline Follow-back method. The researchers also monitored secondary outcomes, including depression, insomnia, and HIV risk behaviors.
By the end of the 12-week study, participants in the mirtazapine group showed a greater reduction in days of methamphetamine use compared to those in the placebo group. Specifically, the mirtazapine group reported an average reduction of 7 days of use, compared to 4.8 days in the placebo group—a net benefit of 2.2 days. While mirtazapine did not significantly improve secondary measures like depression or overall quality of life, the drug was found to be safe for use in routine clinical practice. However, it was associated with more side effects than the placebo, most notably increased drowsiness (47% vs 33%) and weight gain (10% vs 3%).
This trial provides the first phase 3 evidence that mirtazapine can be a viable, safe, and accessible pharmacological tool for managing methamphetamine use disorder. Because mirtazapine is an inexpensive, commonly available generic medication, it can be easily prescribed in outpatient settings without the intensive supervision often required for other, more complex addiction treatments. This suggests a scalable path forward for addressing the global shortage of effective treatments for methamphetamine addiction.
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