Evaluating cognitive effects of topiramate in trauma-focused treatment: Findings from a randomized double-blind clinical trial of veterans with PTSD and alcohol use disorder.

OBJECTIVE: Veterans with comorbid posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD) often experience more severe symptoms, functional impairments, challenges in treatment engagement, and worse treatment outcomes than veterans with either disorder alone. Although topiramate is an effective pharmacotherapy for AUD and has shown promise in reducing PTSD symptoms, concerns about its potential cognitive side effects may deter prescribing providers and contribute to patient hesitancy. This study aimed to determine whether topiramate leads to adverse cognitive side effects that could impede its suitability to be used in tandem with prolonged exposure for PTSD and AUD. METHOD: Data were analyzed from a double-blind, placebo-controlled trial in which 100 veterans with PTSD and AUD were randomized to receive prolonged exposure with either topiramate or placebo. Cognitive functioning was assessed at baseline and midtreatment, and PTSD symptoms were assessed at baseline and posttreatment. RESULTS: Results showed no statistically significant differences between treatment groups in verbal learning and memory or processing speed performance at either time point, and all scores were within normal clinical ranges. CONCLUSIONS: While minor declines in some cognitive domains were observed in both the topiramate and placebo groups, these changes were nonsignificant and not clinically meaningful (<1 standard deviation change). These findings suggest that topiramate does not produce clinically significant cognitive impairment when combined with prolonged exposure and may enhance treatment response. Future research should examine the long-term cognitive and therapeutic effects of topiramate to guide shared decision making and optimize integrated treatment for veterans with PTSD and AUD. (PsycInfo Database Record (c) 2026 APA, all rights reserved).