Examining the Effects of Mirtazapine in Reducing Dependence and Craving for Amphetamine and Methamphetamine: A Clinical Study in Addiction Treatment Patients

Abstract

Background: Methamphetamine use disorder (MUD) is a chronic, relapsing condition associated with increased mortality as well as heightened risk for infectious diseases, including human immunodeficiency virus (HIV) and hepatitis C, in addition to poor mental health outcomes and cardiovascular complications. Despite the global prevalence of amphetamine and methamphetamine use disorder (AMD), no approved pharmacotherapy currently exists for its treatment. Objectives: The present study aimed to evaluate the efficacy of mirtazapine in reducing dependence and craving among patients with AMD. Methods: In this 12-week, double-blind, placebo-controlled randomized clinical trial, 84 patients diagnosed with AMD according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria were recruited from addiction treatment centers in Ahvaz, Iran. Participants were randomly assigned to receive either mirtazapine (15 mg daily, increased to 30 mg after one week) or a matched placebo. Craving and depressive symptoms were assessed using validated questionnaires, including a 20-item craving scale (Cronbach’s α = 0.89) and the Beck Depression Inventory (BDI). Biweekly urine drug tests were performed to monitor methamphetamine use. Statistical analyses included repeated measures analysis of variance (ANOVA) and generalized estimating equations (GEEs). Results: Craving scores in the mirtazapine group decreased from 83.83 to 70.77, whereas the control group exhibited minimal change (from 84.94 to 80.25). Depression scores also declined significantly in the intervention group (from 44.44 to 34.78) compared to controls (from 46.44 to 42.85). These differences were statistically significant for both craving (P = 0.001) and depression (P = 0.003). Reported side effects — including drowsiness, dry mouth, and thirst — were mild and transient. No serious adverse events were observed. Conclusions: Mirtazapine significantly reduced craving and depressive symptoms in patients with AMD, demonstrating good tolerability and no clinically significant side effects. Further multicenter studies with extended follow-up periods are recommended to confirm these findings and to assess relapse rates.