Nefazodone in the Treatment of Generalized Social Phobia: A Randomized, Placebo-Controlled Trial

Michael Van Ameringen, M.D., F.R.C.P.C.; Catherine Mancini, M.D., F.R.C.P.C.; Jonathan Oakman, Ph.D.; John Walker, Ph.D.; Kevin Kjernisted, M.D., F.R.C.P.C.; Pratap Chokka, M.D., F.R.C.P.C.; David Johnston, M.D., F.R.C.P.C.; Mark Bennett, B.A.; and Beth Patterson, B.Sc.N., B.Ed.

Objective: Numerous studies have demonstrated the efficacy of serotonergic antidepressants, particularly the selective serotonin reuptake inhibitors (SSRIs), in the treatment of social phobia. We evaluated the efficacy, safety, and tolerability of nefazodone, a 5-HT₂ antagonist, in patients with generalized social phobia (GSP).

Method: One hundred five patients with GSP (confirmed using the Structured Clinical Interview for DSM-IV) from 4 Canadian outpatient anxiety clinics were assigned randomly to nefazodone (300-600 mg/day, flexible dose) or placebo for 14 weeks of double-blind treatment. Data were collected from October 12, 1999, through December 8, 2001. Primary efficacy outcomes were the Clinical Global Impressions-Improvement scale (CGI-I) score and the Liebowitz Social Anxiety Scale score.

Results: In the intent-to-treat sample, 16 (31.4%) of 51 subjects taking nefazodone and 12 (23.5%) of 51 subjects taking placebo were rated as much or very much improved on the CGI-I at endpoint (chi² = 0.79, p = .38). With the exception of the Social Phobia Scale, no significant differences were found in measures of social phobia when comparing the nefazodone and placebo groups.

Conclusion: These findings suggest that nefazodone is not an effective agent in the treatment of GSP. These data parallel some recent findings with the use of the SSRI fluoxetine in GSP. The lack of efficacy of 2 serotonergic antidepressants in GSP suggests that serotonin reuptake inhibition may not be the only mechanism of action required for efficacy to occur in the treatment of GSP.

(J Clin Psychiatry 2007;68:288-295)

Received Dec. 12, 2005; accepted July 3, 2006. From the Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Ontario (Drs. Van Ameringen and Mancini); the University of Waterloo, Waterloo, Ontario (Dr. Oakman); the Department of Clinical Health Psychology (Dr. Walker) and the Department of Psychiatry (Dr. Kjernisted), University of Manitoba, Winnipeg, Manitoba; the Department of Psychiatry, Grey Nuns Community Hospital and Health Centre, Edmonton, Alberta (Dr. Chokka); the Department of Psychiatry, University of Calgary, Calgary, Alberta (Dr. Johnston); and the Anxiety Disorders Clinic, McMaster University Medical Centre, Hamilton Health Services, Hamilton, Ontario (Mr. Bennett and Ms. Patterson), Canada.

Partial funding for this study was provided by an investigator-initiated research grant from Bristol-Myers Squibb, Montreal, Quebec, Canada.

Dr. Van Ameringen has received grant/research support from AstraZeneca, Cephalon, GlaxoSmithKline, Janssen-Ortho Inc., National Institutes of Health, Novartis, Pfizer, and Wyeth-Ayerst; has served as a consultant for Biovail, Cephalon, GlaxoSmithKline, Janssen-Ortho Inc., Novartis, Pfizer, and Wyeth-Ayerst; and has served on the speakers bureaus of GlaxoSmithKline, Janssen-Ortho Inc., Pfizer, and Wyeth-Ayerst. Dr. Mancini has received grant/research support from Astra Zeneca, Cephalon, GlaxoSmithKline, Eli Lilly, Janssen-Ortho Inc., National Institutes of Health, Novartis, and Pfizer and has served as a consultant for and on the speakers bureau of GlaxoSmithKline. Drs. Oakman, Walker, Kjernisted, Chokka, and Johnston and Mr. Bennett and Ms. Patterson report no other financial affiliations relevant to the subject of this article.

Corresponding author and reprints: Michael Van Ameringen, M.D., F.R.C.P.C., Anxiety Disorders Clinic, 3G Clinic, McMaster University Medical Centre, Hamilton Health Sciences, 1200 Main St., West, Hamilton, Ontario, L8N 3Z5, Canada (e-mail: vanamer@mcmaster.ca).