Does Topiramate Add-On Enhance the Response to the MATRIX Program in Individuals with Methamphetamine Use Disorder? A Double-Blinded Randomized Placebo-Controlled Trial

Background: Methamphetamine dependence significantly impacts individuals and society. Treating methamphetamine use disorder is challenging due to limited evidence on effective pharmacotherapies and their interaction with nonpharmacologic interventions. This study evaluated the efficacy of topiramate compared to placebo in treating methamphetamine use disorder among participants in a Matrix program. Methods: Participants were recruited from the Addiction Center of Iran Psychiatric Hospital between January 2020 and June 2023 and randomly assigned to receive either topiramate or a placebo for 12 weeks, alongside Matrix program sessions. Blinding was maintained for participants, personnel, outcome assessors, and statisticians. Main outcomes included craving, desire to use, positive urine amphetamine toxicology rates, and depression severity. Craving was assessed using the Visual Analog Scale (VAS) and the Substance Craving Questionnaire–brief (SCQ-B). The desire to use was evaluated with the Addiction Severity Index (ASI), while depression severity was measured using the Beck Depression Inventory. Data analysis utilized IBM SPSS Statistics® 20.0, employing various statistical tests for comparison. Results: Both groups exhibited improvement in craving as per VAS scores (p=0.007), with greater reduction in the topiramate group; however, no significant difference was found between groups (p=0.06). The negative urine toxicology rates showed no significant difference (Hazard ratio=1.15, 95% CI: 0.75, 1.78). Depression scores decreased in both groups without significant between-group differences (p=0.78). Conclusion: The findings do not support the efficacy of topiramate in enhancing outcomes within a Matrix program for individuals with methamphetamine use disorder.