Nefazodone in the treatment of generalized social phobia: a randomized, placebo-controlled trial.

Objective: Numerous studies have demonstrated the efficacy of serotonergic antidepres-sants, particularly the selective serotonin reuptake inhibitors (SSRIs), in the treatment of social phobia. We evaluated the efficacy, safety, and tolerability of nefazodone, a 5-HT(2) 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 (chi(2) = 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.