Topiramate Monotherapy for Civilian Posttraumatic Stress Disorder: A Controlled Pilot Study

Varun Monga, MD; Frederick Petty, PhD, MD; Kalpana Padala, MD; Prasad R. Padala, MD

Prim Care Companion CNS Disord 2023;25(5):23m03555

ABSTRACT

Objective: To assess the efficacy, safety, and tolerability of topiramate for the treatment of posttraumatic stress disorder (PTSD) in civilians.

Methods: This 12-week double-blind, randomized, placebo-controlled study enrolled 72 outpatients (aged 19–64 years) with a DSM-IV-TR diagnosis of non–combat-related PTSD and a score ≥ 50 on the Clinician-Administered PTSD Scale (CAPS). The primary efficacy endpoint, percent change in total CAPS score, and secondary efficacy measures were assessed by analysis of covariance. Safety assessments included monitoring of vital signs, physical examinations, clinical laboratory parameters, electrocardiograms, and adverse events (AEs). The study was conducted from October 2001 to March 2004.

Results: The intent-to-treat (ITT) population (N = 68; mean age = 35 years; 87% women; 74% White) showed greater percent reduction in total CAPS scores with topiramate versus placebo (39.5% vs 29.5%), but the difference was not statistically significant (P = .31). Similarly, higher reductions with topiramate versus placebo were seen in the CAPS subscale scores for symptoms of reexperiencing (43.6% vs 34.8%), avoidance/numbing (38.3% vs 30.6%), and hyperarousal (36.6% vs 21.4%). However, these differences were not statistically significant. Six patients in the topiramate arm had a final CAPS score < 20, whereas only 2 in the placebo arm achieved the result (P = .075). The median final topiramate daily dose was 100 mg/d (range, 25–400 mg/d), and mean ± SD treatment duration was 55 ± 32 days, showing the tolerability of the medication. In topiramate-treated patients, treatment-emergent AEs included paresthesia, headache, fatigue, and insomnia; treatment-limiting AEs included influenza-like symptoms, agitation, cognitive problems not otherwise specified, and somnolence. However, a higher rate of AE-related discontinuation was seen in the placebo group than in the treatment group (26% vs 18%).

Conclusions: In this 12-week civilian PTSD study, topiramate improved the primary and secondary outcome measures at a higher rate than did placebo, but the difference did not reach statistical significance. Further adequately powered studies may be warranted.

Trial Registration: Clinical Trials.gov identifier: NCT00208130

Prim Care Companion CNS Disord 2023;25(5):23m03555

Author affiliations are listed at the end of this article.

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References (45)

Kilpatrick DG, Resnick HS, Milanak ME, et al. National estimates of exposure to traumatic events and PTSD prevalence using DSM-IV and DSM-5 criteria. J Trauma Stress. 2013;26(5):537–547. PubMed CrossRef
Koenen KC, Ratanatharathorn A, Ng L, et al. Posttraumatic stress disorder in the World Mental Health Surveys. Psychol Med. 2017;47(13):2260–2274. PubMed CrossRef
Javidi H, Yadollahie M. Post-traumatic stress disorder. Int J Occup Environ Med. 2012;3(1):2–9. PubMed
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR). Washington, DC: American Psychiatric Association; 2000.
Ressler KJ, Berretta S, Bolshakov VY, et al. Post-traumatic stress disorder: clinical and translational neuroscience from cells to circuits. Nat Rev Neurol. 2022;18(5):273–288. PubMed CrossRef
Zoloft (sertraline HCl) Tablets and Oral Concentrate, prescribing information. New York: Roerig/Pfizer; 2011. https://labeling.pfizer.com/ShowLabeling.aspx?id=517.
Paxil (paroxetine HCl) Tablets and Oral Suspension, prescribing information. Research Triangle Park, N.C: GlaxoSmithKline; 2011. http://us.gsk.com/products/assets/us_paxil.pdf.
Davidson JR, Rothbaum BO, van der Kolk BA, et al. Multicenter, double-blind comparison of sertraline and placebo in the treatment of posttraumatic stress disorder. Arch Gen Psychiatry. 2001;58(5):485–492. PubMed CrossRef
Brady K, Pearlstein T, Asnis GM, et al. Efficacy and safety of sertraline treatment of posttraumatic stress disorder: a randomized controlled trial. JAMA. 2000;283(14):1837–1844. PubMed CrossRef
Tucker P, Zaninelli R, Yehuda R, et al. Paroxetine in the treatment of chronic posttraumatic stress disorder: results of a placebo-controlled, flexible-dosage trial. J Clin Psychiatry. 2001;62(11):860–868. PubMed CrossRef
Connor KM, Sutherland SM, Tupler LA, et al. Fluoxetine in post-traumatic stress disorder: randomised, double-blind study. Br J Psychiatry. 1999;175(1):17–22. PubMed CrossRef
Martenyi F, Brown EB, Caldwell CD. Failed efficacy of fluoxetine in the treatment of posttraumatic stress disorder: results of a fixed-dose, placebo-controlled study. J Clin Psychopharmacol. 2007;27(2):166–170. PubMed CrossRef
Davidson J, Kudler H, Smith R, et al. Treatment of posttraumatic stress disorder with amitriptyline and placebo. Arch Gen Psychiatry. 1990;47(3):259–266. PubMed CrossRef
Reist C, Kauffmann CD, Haier RJ, et al. A controlled trial of desipramine in 18 men with posttraumatic stress disorder. Am J Psychiatry. 1989;146(4):513–516. PubMed CrossRef
Baker DG, Diamond BI, Gillette G, et al. A double-blind, randomized, placebo-controlled, multi-center study of brofaromine in the treatment of post-traumatic stress disorder. Psychopharmacology (Berl). 1995;122(4):386–389. PubMed CrossRef
Frank JB, Kosten TR, Giller EL Jr, et al. A randomized clinical trial of phenelzine and imipramine for posttraumatic stress disorder. Am J Psychiatry. 1988;145(10):1289–1291. PubMed CrossRef
Ramaswamy S, Driscoll D, Reist C, et al. A double-blind, placebo-controlled randomized trial of vilazodone in the treatment of posttraumatic stress disorder and comorbid depression. Prim Care Companion CNS Disord. 2017;19(4):17m02138. PubMed CrossRef
Krystal JH, Rosenheck RA, Cramer JA, et al; Veterans Affairs Cooperative Study No. 504 Group. Adjunctive risperidone treatment for antidepressant-resistant symptoms of chronic military service-related PTSD: a randomized trial. JAMA. 2011;306(5):493–502. PubMed CrossRef
Carey P, Suliman S, Ganesan K, et al. Olanzapine monotherapy in posttraumatic stress disorder: efficacy in a randomized, double-blind, placebo-controlled study. Hum Psychopharmacol. 2012;27(4):386–391. PubMed CrossRef
Padala PR, Madison J, Monnahan M, et al. Risperidone monotherapy for post-traumatic stress disorder related to sexual assault and domestic abuse in women. Int Clin Psychopharmacol. 2006;21(5):275–280. PubMed CrossRef
Adamou M, Puchalska S, Plummer W, et al. Valproate in the treatment of PTSD: systematic review and meta analysis. Curr Med Res Opin. 2007;23(6):1285–1291. PubMed CrossRef
Davis LL, Davidson JR, Ward LC, et al. Divalproex in the treatment of posttraumatic stress disorder: a randomized, double-blind, placebo-controlled trial in a veteran population. J Clin Psychopharmacol. 2008;28(1):84–88. PubMed CrossRef
Wang HR, Woo YS, Bahk WM. Anticonvulsants to treat post-traumatic stress disorder. Hum Psychopharmacol. 2014;29(5):427–433. PubMed CrossRef
Hertzberg MA, Butterfield MI, Feldman ME, et al. A preliminary study of lamotrigine for the treatment of posttraumatic stress disorder. Biol Psychiatry. 1999;45(9):1226–1229. PubMed CrossRef
Hamner MB, Brodrick PS, Labbate LA. Gabapentin in PTSD: a retrospective, clinical series of adjunctive therapy. Ann Clin Psychiatry. 2001;13(3):141–146. PubMed CrossRef
Keck PE Jr, McElroy SL, Friedman LM. Valproate and carbamazepine in the treatment of panic and posttraumatic stress disorders, withdrawal states, and behavioral dyscontrol syndromes. J Clin Psychopharmacol. 1992;12(Suppl):36S–41S. PubMed CrossRef
Lipper S, Davidson JR, Grady TA, et al. Preliminary study of carbamazepine in post-traumatic stress disorder. Psychosomatics. 1986;27(12):849–854. PubMed CrossRef
Looff D, Grimley P, Kuller F, et al. Carbamazepine for PTSD. J Am Acad Child Adolesc Psychiatry. 1995;34(6):703–704. PubMed CrossRef
Latini G, Verrotti A, Manco R, et al. Topiramate: its pharmacological properties and therapeutic efficacy in epilepsy. Mini Rev Med Chem. 2008;8(1):10–23. PubMed CrossRef
Bai YF, Zeng C, Jia M, et al. Molecular mechanisms of topiramate and its clinical value in epilepsy. Seizure. 2022;98:51–56. PubMed CrossRef
Fariba KA, Saadabadi A. Topiramate. In: StatPearls. Treasure Island, FL: StatPearls Publishing; January 31, 2023.
Blake DD, Weathers FW, Nagy LM, et al. The development of a clinician-administered PTSD scale. J Trauma Stress. 1995;8(1):75–90. PubMed CrossRef
Blake D, Weathers F, Nagy L, et al. Clinician-Administered PTSD Scale (CAPS). Instruction Manual; 2000:1–149.
Hamilton M. The assessment of anxiety states by rating. Br J Psychol. 1959;32(1):50–55. CrossRef
Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry. 1960;23(1):56–62. PubMed CrossRef
Davidson JR, Colket JT. The eight-item treatment-outcome post-traumatic stress disorder scale: a brief measure to assess treatment outcome in post-traumatic stress disorder. Int Clin Psychopharmacol. 1997;12(1):41–46. PubMed CrossRef
Guy W. Clinical Global Improvement Scale. ECDEU Assessment Manual for Psychopharmacology. US Dept Health, Education, and Welfare; Rockville, MD: 1976:218-222
Leon AC, Davis LL. Enhancing clinical trial design of interventions for posttraumatic stress disorder. J Trauma Stress. 2009;22(6):603–611. PubMed CrossRef
Halvorsen JØ. Defining clinically significant change. Br J Psychiatry. 2016;209(1):85. PubMed CrossRef
Institute of Medicine. Treatment of Posttraumatic Stress Disorder: An Assessment of the Evidence. National Academies Press; 2008:224.
Tucker P, Trautman RP, Wyatt DB, et al. Efficacy and safety of topiramate monotherapy in civilian posttraumatic stress disorder: a randomized, double-blind, placebo-controlled study. J Clin Psychiatry. 2007;68(2):201–206. PubMed CrossRef
Yeh MS, Mari JJ, Costa MC, et al. A double-blind randomized controlled trial to study the efficacy of topiramate in a civilian sample of PTSD. CNS Neurosci Ther. 2011;17(5):305–310. PubMed CrossRef
Berlant JL. Prospective open-label study of add-on and monotherapy topiramate in civilians with chronic nonhallucinatory posttraumatic stress disorder. BMC Psychiatry. 2004;4(24):24. PubMed CrossRef
Berlant J, van Kammen DP. Open-label topiramate as primary or adjunctive therapy in chronic civilian posttraumatic stress disorder: a preliminary report. J Clin Psychiatry. 2002;63(1):15–20. PubMed CrossRef
Lindley SE, Carlson EB, Hill K. A randomized, double-blind, placebo-controlled trial of augmentation topiramate for chronic combat-related posttraumatic stress disorder. J Clin Psychopharmacol. 2007;27(6):677–681. PubMed CrossRef