Antidepressant Shows Promise in Reducing Methamphetamine Use

Apr 6, 2026

The Tina Trial, published in JAMA Psychiatry, found that the antidepressant mirtazapine helped 339 methamphetamine-dependent Australians reduce their use by an average of 7 days per month compared to 4.8 days for placebo recipients, representing a 2.2-day advantage. The finding is significant because an estimated 7.4 million people worldwide depend on methamphetamine, yet no medications are approved anywhere to treat this condition, and Australia has one of the highest per capita dependence rates globally. Mirtazapine offers practical advantages as a take-home, off-patent medication that doctors already know from depression treatment, and it worked regardless of whether patients had depression. The results build on two smaller San Francisco trials and could lead to the first approved pharmacological treatment for methamphetamine dependence, addressing high dropout and relapse rates in current counseling and rehabilitation programs.

Mirtazapine trial results and effectiveness

▪The Tina Trial recruited 339 people dependent on methamphetamine from six outpatient clinics in Australia.
▪Both previous San Francisco mirtazapine trials found mirtazapine reduced methamphetamine use.
▪Previous San Francisco mirtazapine trials excluded women and people with depression.
▪Tina Trial participants had used methamphetamine an average of 22 days out of the previous 28 days at the start of the trial.
▪Previous San Francisco mirtazapine trials recruited patients at risk of HIV who were men and transgender women who had sex with men.
▪People who received mirtazapine in the Tina Trial reduced their methamphetamine use by an average of 7 days out of 28 days.
▪Mirtazapine showed a comparative advantage over placebo of 2.2 days reduction in methamphetamine use out of 28 days in the Tina Trial.
▪Tina Trial participants received either 30 milligrams of mirtazapine daily or a placebo for 12 weeks.
▪Two previous mirtazapine trials were conducted in an outpatient research clinic in San Francisco, California with 60 and 120 patients respectively.
▪Mirtazapine's benefit in reducing methamphetamine use was apparent regardless of whether people had depression at the start of the Tina Trial.

Current treatment landscape for methamphetamine dependence

▪An estimated 7.4 million people in the world are dependent on methamphetamine.
▪There are no medications approved anywhere in the world to treat methamphetamine dependence.

Safety profile and practical implementation considerations

▪Guidelines on off label prescribing of medications are available from the Royal Australian New Zealand College of Psychiatrists.
▪The most common side effects of mirtazapine in the Tina Trial were drowsiness and weight gain.
▪The Tina Trial found no unexpected safety issues when using mirtazapine to treat methamphetamine dependence.

Perspective of Methamphetamine treatment researchers

▪Mirtazapine represents a potential first approved medication for methamphetamine dependence globally.
▪The Tina Trial's larger scale and more diverse participant pool strengthens the evidence base compared to previous San Francisco trials.

Perspective of Australian public health officials

▪The Tina Trial's Australian setting provides locally relevant evidence for potential policy decisions on mirtazapine approval.

Perspective of Practicing physicians treating addiction

▪Off-label prescribing guidelines from the Royal Australian New Zealand College of Psychiatrists provide a framework for physicians to use mirtazapine before formal approval.
▪The absence of unexpected safety issues in the Tina Trial provides reassurance for physicians considering off-label mirtazapine prescribing.