A randomized, double-blind, placebo-controlled trial of augmentation topiramate for chronic combat-related posttraumatic stress disorder

Background: Topiramate, a novel anticonvulsant, has been reported to rapidly reduce symptoms of posttraumatic stress disorder (PTSD) in an open-label trial. The present study was designed as a test of topiramate's efficacy as adjunctive therapy in a 7-week, randomized, double-blind, placebo-controlled trial. Methods: Forty male veterans with PTSD in a residential treatment program were randomized to flexible-dose topiramate or placebo augmentation. The primary outcome measures were PTSD symptom severity and global symptom improvement. Results: Baseline Clinician-Administered PTSD Scale scores were 62.1 +/- 13.9 for placebo and 61.0 +/- 22.2 for topiramate. There was a high dropout rate from the study (55% topiramate; 25% placebo), with 40% of topiramate and 10% of placebo dropping because of adverse events (AEs). No significant treatment effects of topiramate versus placebo were observed for the primary treatment outcomes. Subjects reporting central nervous system-related AEs and with higher baseline severity of depression were more likely to discontinue because of AEs. Conclusions: Primary outcome measures failed to demonstrate a significant effect for topiramate over placebo; however, high dropout rate in the treatment group prohibits definitive conclusions about the efficacy of topiramate in this population.