An Open Trial of Topiramate in the Treatment of Generalized Social Phobia

Michael Van Ameringen, M.D., F.R.C.P.C.; Catherine Mancini, M.D., F.R.C.P.C.; Beth Pipe, B.Sc.N, B.Ed.; Jonathan Oakman, Ph.D., C.Psych.; and Mark Bennett, B.A.

Background: Selective serotonin reuptake inhibitors (SSRIs) are the current gold standard in the pharmacologic treatment of generalized social phobia. SSRIs are only effective in approximately 50% of individuals with generalized social phobia and can be associated with significant side effects. Based on the successful use of the anticonvulsants gabapentin and pregabalin in treating generalized social phobia, we conducted an open trial examining the efficacy of the glutamatergic and GABAergic anticonvulsant topiramate in the treatment of generalized social phobia.

Method: Twenty-three adult outpatients with DSM-IV social phobia, generalized type, were entered into a 16-week open trial of topiramate, starting at 25 mg/day, and gradually titrated up to a maximum dose of 400 mg/day.

Results: Twelve of 23 patients completed the trial. In the intent-to-treat (ITT) analysis, 11 (47.8%) of 23 were responders by a Clinical Global Impressions Improvement (CGI-I) scale rating of "much" or "very much" improved. The mean drop in the Liebowitz Social Anxiety Scale (LSAS) score for the ITT group was 29.4%. The change in LSAS score from baseline to endpoint was significant for the ITT group (F = 3.44, df = 4,110; p = .01). In the completers group, 9 (75.0%) of 12 were responders by CGI-I at 16 weeks, with a mean drop in LSAS score of 45.1%. The rate of remission in the ITT sample, using a definition of an LSAS score of <= 30, gave a remission rate of 26.1% (6/23).

Conclusion: This study suggests that topiramate may be effective in the treatment of generalized social phobia. These results also suggest the possibility that the neurotransmitters glutamate and GABA may be involved in the neurobiology of generalized social phobia.

(J Clin Psychiatry 2004;65:1674-1678)

Received Dec. 22, 2003; accepted April 28, 2004. From the Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton (Drs. Van Ameringen and Mancini); the Anxiety Disorders Clinic, McMaster University Medical Centre of Hamilton Health Sciences, Hamilton (Drs. Van Ameringen and Mancini, Ms. Pipe, and Mr. Bennett); and the Department of Psychology, University of Waterloo, Waterloo (Dr. Oakman), Ontario, Canada.

Partial funding for this study was provided by Janssen Ortho Inc., Toronto, Ontario, Canada.

Dr. Van Ameringen has been a consultant for Cephalon, GlaxoSmithKline, Novartis, Pfizer, Solvay, Wyeth-Ayerst, Biovail, and Lundbeck; has received grant/research support from AstraZeneca, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen-Ortho, Lundbeck, Pfizer, and Wyeth-Ayerst; and has participated in speakers/advisory boards for GlaxoSmithKline, Janssen-Ortho, and Pfizer. Dr. Mancini has been a consultant for GlaxoSmithKline and Wyeth-Ayerst; has received grant/research support from AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Eli Lilly, Janssen-Ortho, Lundbeck, Pfizer, and Wyeth-Ayerst; and has participated in speakers/advisory boards for GlaxoSmithKline.

Corresponding author and reprints: M. Van Ameringen, M.D., Anxiety Disorders Clinic, 3G Clinic, McMaster University Medical Centre, Hamilton Health Sciences, Box 2000, Hamilton, Ontario, Canada, L8N 3Z5 (e-mail: vanamer@mcmaster.ca).