Urine Screening Outcomes in Amphetamine and Methamphetamine Use Disorder Treated with Mirtazapine: A Double-Blind Placebo-Controlled Study in Iran

Abstract

Background: Amphetamine and methamphetamine use disorders are associated with significant psychiatric and social consequences, and effective pharmacological treatments remain limited. Objectives: This study was conducted in male participants in Iran to evaluate the efficacy of mirtazapine in reducing stimulant use, depressive symptoms, and craving intensity among individuals with stimulant use disorder. Methods: In a 12-week, double-blind, randomized controlled trial, 84 male participants diagnosed with amphetamine or methamphetamine use disorder were assigned to receive either mirtazapine (30 mg/day) or placebo. Depressive symptoms were assessed using the Beck Depression Inventory-II (BDI-II). Participants were excluded only based on the clinical diagnosis of severe major depressive disorder, not solely on the BDI-II score. Urine drug screens were conducted biweekly (Session 1–6, with Session 6 corresponding to Week 12), and craving was measured using the Persian Stimulant Craving Questionnaire (14 items; score range 14 - 140). Adverse events were actively monitored at each visit and categorized by severity and duration. Results: By Week 12, 52.4% of participants in the mirtazapine group tested negative for amphetamines, compared to 9.5% in the placebo group (P = 0.007). BDI-II scores decreased from 44.44 ± 13.37 to 34.78 ± 10.06 in the mirtazapine group, while the placebo group showed minimal change. Craving scores declined from 83.83 ± 17.48 to 70.77 ± 12.75 in the mirtazapine group versus 84.94 ± 9.70 to 80.25 ± 12.57 in the placebo group. Mirtazapine was well tolerated, with no serious adverse events reported. Conclusions: Mirtazapine demonstrated potential effectiveness in reducing stimulant use, alleviating depressive symptoms, and decreasing craving in male participants with amphetamine or methamphetamine use disorder. These findings are limited to men over 12 weeks, and further studies are required to evaluate long-term safety, functional outcomes, and effectiveness in diverse populations. While the results support its possible role as an adjunctive treatment in addiction care, caution is advised due to the short-term nature of the trial and the absence of functional outcome measures.