The Antidepressant, Mirtazapine, Help Manage Methamphetamine Use Disorder
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Reviewed & Translated by Dat Tien Nguyen, B.A, ScM.
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Posted on May 8th, 2026
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Methamphetamine addiction imposes a major burden on both healthcare systems and society. Chronic methamphetamine use has been associated with increased risks of psychosis, cardiovascular disease, and a range of psychiatric disorders. Given the limited pharmacologic options available for methamphetamine use disorder, a recent study published in the Journal of the American Medical Association evaluated the potential role of mirtazapine in reducing methamphetamine use.
Funding Source(s): Australian Government’s Medical Research Future Fund
The phase 3 clinical trial was conducted in Australia and New Zealand and enrolled 339 participants with a mean age of 42 years who had moderate to severe methamphetamine use disorder. On average, participants reported methamphetamine use on approximately 24 of the previous 28 days. Nearly 45% administered the drug by injection, and some participants also reported concurrent use of other substances, although these were not further characterized in the study.
Participants were randomly assigned to receive either placebo or oral mirtazapine at a daily dose of 30 mg. Mirtazapine is a tetracyclic antidepressant commonly used to treat major depressive disorder. Its pharmacologic effects include antagonism of adrenergic and serotonergic receptors, which can increase dopaminergic signaling in the prefrontal cortex. Researchers hypothesized that this mechanism might help counteract the dopaminergic dysregulation associated with methamphetamine dependence. In addition, mirtazapine blocks histamine H1 receptors, which may improve associated symptoms such as insomnia and anxiety.
After 12 weeks of treatment, patients receiving mirtazapine reduced methamphetamine use by an average of seven days per month, compared with a reduction of 4.8 days in the placebo group. However, mirtazapine did not significantly improve depressive symptoms, insomnia, or overall quality of life measures. Treatment discontinuation due to adverse effects was also more common in the mirtazapine group. Despite this limitation, the investigators noted that the relatively low cost, established safety profile, and modest clinical benefit of mirtazapine make it a potentially useful adjunctive treatment option for methamphetamine use disorder.
Funding Source(s): Australian Government’s Medical Research Future Fund
The phase 3 clinical trial was conducted in Australia and New Zealand and enrolled 339 participants with a mean age of 42 years who had moderate to severe methamphetamine use disorder. On average, participants reported methamphetamine use on approximately 24 of the previous 28 days. Nearly 45% administered the drug by injection, and some participants also reported concurrent use of other substances, although these were not further characterized in the study.
Participants were randomly assigned to receive either placebo or oral mirtazapine at a daily dose of 30 mg. Mirtazapine is a tetracyclic antidepressant commonly used to treat major depressive disorder. Its pharmacologic effects include antagonism of adrenergic and serotonergic receptors, which can increase dopaminergic signaling in the prefrontal cortex. Researchers hypothesized that this mechanism might help counteract the dopaminergic dysregulation associated with methamphetamine dependence. In addition, mirtazapine blocks histamine H1 receptors, which may improve associated symptoms such as insomnia and anxiety.
After 12 weeks of treatment, patients receiving mirtazapine reduced methamphetamine use by an average of seven days per month, compared with a reduction of 4.8 days in the placebo group. However, mirtazapine did not significantly improve depressive symptoms, insomnia, or overall quality of life measures. Treatment discontinuation due to adverse effects was also more common in the mirtazapine group. Despite this limitation, the investigators noted that the relatively low cost, established safety profile, and modest clinical benefit of mirtazapine make it a potentially useful adjunctive treatment option for methamphetamine use disorder.