Mirtazapine reduced methamphetamine use days compared with placebo in patients with moderate to severe methamphetamine use disorder in a phase 3 randomized clinical trial conducted in outpatient settings.

In the double-blind, placebo-controlled trial conducted across six clinics in Australia, 339 patients received mirtazapine 30 mg daily or placebo for 12 weeks. Patients reported methamphetamine use on a median of 24 of the past 28 days at baseline.

By week 12, methamphetamine use decreased by 7 days in the mirtazapine group vs 4.8 days in the placebo group. This corresponded to an 8% lower risk of methamphetamine use on a given day with mirtazapine.

Key Findings

• Mean reduction across follow-up time points was 1.8 fewer days of use

• No statistically significant differences were observed in depression, insomnia, HIV risk behavior, quality of life, or methamphetamine-negative oral fluid samples

• Adverse events were more common with mirtazapine, including drowsiness (47% vs 33%) and weight gain (10% vs 3%).

Subgroup Findings

• Reductions in methamphetamine use were similar across sex and depression status

• Among patients with baseline depression, mirtazapine was associated with greater reductions in insomnia scores at multiple  time points.

Safety

• Discontinuation due to adverse events occurred in 23% of patients receiving mirtazapine vs 15% receiving placebo

• Serious adverse events occurred in 5% of patients  and were not treatment-related.

Study Limitations

The researchers noted that treatment effects may have been attenuated by heterogeneous patient characteristics, moderate medication adherence, and discontinuation rates in routine clinical practice

The outpatient design improves generalizability but may dilute treatment effects compared with earlier controlled trials

“Mirtazapine can be used in routine clinical practice to facilitate a reduction in methamphetamine use among people with a moderate to severe methamphetamine use disorder,” wrote lead study author Rebecca McKetin, PhD, of the University of New South Wales, Sydney, Australia, and colleagues.

Disclosures: McKetin reported grants from the Medical Research Future Fund during the conduct of the study. Several co-researchers reported grants, consulting fees, speaker honoraria, advisory board fees, employment support, shares, or patents outside the submitted work. No other disclosures were reported.

Source: JAMA Psychiatry