Efficacy and Safety of Topiramate Monotherapy in Civilian Posttraumatic Stress Disorder: A Randomized, Double-Blind, Placebo-Controlled Study

Phebe Tucker, M.D.; Richard P. Trautman, M.D.; Dorothy B. Wyatt, R.N.; Jamie Thompson; Shu-Chen Wu, Ph.D.; Julie A. Capece, B.A.; and Norman R. Rosenthal, M.D. 

Objective: This double-blind, placebo-controlled trial assessed efficacy and safety of topiramate monotherapy in civilian posttraumatic stress disorder (PTSD).

Method: Outpatients (18-64 years) with DSM-IV non-combat-related PTSD and Clinician-Administered PTSD Scale (CAPS) scores >= 50 were eligible. Topiramate was started at 25 mg/day and titrated by 25-50 mg/week to 400 mg/day or maximum tolerated dose. Data were collected between April 26, 2002, and February 4, 2004. Primary efficacy, change in total CAPS score, and secondary efficacy measures were assessed by analysis of covariance in the intent-to-treat (ITT) population with last observation carried forward.

Results: The ITT population comprised 38 patients with mean ± SD baseline total CAPS scores of 88.3 ± 13.8 (topiramate, N = 19) and 91.1 ± 13.7 (placebo, N = 19). Although a decrease in total CAPS score was noted (topiramate, -52.7; placebo, -42.0), this difference was not statistically significant (p = .232). Topiramate-treated patients exhibited significant reductions in reexperiencing symptoms (CAPS cluster B: topiramate, 74.9%; placebo, 50.2%; p = .038) and Treatment Outcome PTSD scale (topiramate, 68.0%; placebo, 41.6%; p = .025). Reductions approaching statistical significance, based on a nominal p value, were noted in mean total Clinical Global Impressions-Improvement Scale scores (topiramate, 1.9 ± 1.2; placebo, 2.6 ± 1.1; p = .055).

Conclusion: These preliminary results suggest that further, adequately powered studies of topiramate for the treatment of civilian PTSD are warranted.

(J Clin Psychiatry 2007;68:201-206)

Received Oct. 19, 2005; accepted June 20, 2006. From the Department of Psychiatry and Behavioral Sciences, Oklahoma Health Sciences Center, University of Oklahoma, Oklahoma City (Drs. Tucker and Trautman and Mss. Wyatt and Thompson); Ortho-McNeil Pharmaceuticals (Johnson & Johnson), Raritan, N. J. (Dr. Wu); the Department of Clinical Operations, Ortho-McNeil Neurologics, Inc., Titusville, N.J. (Ms. Capece); and the Department of Medical Affairs, PriCara, Unit of Ortho-McNeil Inc., Raritan, N.J. (Dr. Rosenthal). Dr. Wu is now with the Department of Biostatistics, Scios Inc. (Johnson & Johnson), Fremont, Calif.

This study was supported by Ortho-McNeil Neurologics, Inc., Titusville, N.J.

Data were presented at the Anxiety Disorders Association of America 25th annual conference, March 2005, Seattle, Wa., and the 2005 American Psychiatric Association annual meeting, May 2005, Atlanta, Ga.

Dr. Tucker has been a consultant for Ortho-McNeil; has received grant/research support or honoraria from AstraZeneca, Bristol-Myers Squibb, Ortho-McNeil, Otsuka, Pfizer, GlaxoSmithKline, and Cephalon; and has been on the speaker/advisory board of GlaxoSmithKline. Dr. Trautman has received grant/research support from Pfizer, Apotex, GlaxoSmithKline, Ortho-McNeil, and Cephalon. Drs. Wu and Rosenthal and Ms. Capece were employees of Ortho-McNeil when the study was conducted. Mss. Wyatt and Thompson have no additional relevant financial or other affiliations.

Corresponding author and reprints: Phebe Tucker, M.D., University of Oklahoma Health Sciences Center, 920 S.L. Young Blvd., WP3440, Oklahoma City, OK 73104 (e-mail: phebe-tucker@ouhsc.edu).