The International Journal of Neuropsychopharmacology

Fluvoxamine CR in the long-term treatment of social anxiety disorder: the 12- to 24-week extension phase of a multicentre, randomized, placebo-controlled trial

Dan J. Stein a1c1, Herman G. M. Westenberg a2, Haichen Yang a3, David Li a3 and Luigi M. Barbato a3
a1 MRC Unit on Anxiety Disorders, University of Stellenbosch, Cape Town, South Africa, and University of Florida, Gainesville, FL, USA
a2 Department of Biological Psychiatry, University Hospital Utrecht, The Netherlands
a3 Clinical Operations and Medical Affairs, Solvay Pharmaceuticals, Inc., Marietta, GA, USA

Article author query
stein d   [PubMed][Google Scholar] 
westenberg h   [PubMed][Google Scholar] 
yang h   [PubMed][Google Scholar] 
li d   [PubMed][Google Scholar] 
barbato l   [PubMed][Google Scholar] 


Fluvoxamine CR has been reported effective in the short-term (12-wk) treatment of generalized social anxiety disorder (social phobia). Social anxiety disorder (SAD) is, however, a chronic disorder thought to require maintenance treatment. We report on data from the extension phase of a short-term study, in order to explore the efficacy and safety profile of fluvoxamine CR (100–300 mg/d) in the longer-term treatment of this disorder. Adult outpatients with generalized social anxiety disorder (GSAD) at 35 centres in Europe, South Africa, and USA were included in an acute phase study (12 wk). Subjects who demonstrated at least minimal improvement by endpoint (n=112), were offered participation in an extension phase, in which medication was continued for a further 12 wk under double-blind conditions. Efficacy was assessed using the Liebowitz Social Anxiety Disorder Scale (LSAS), the Clinical Global Impression Global Improvement score (CGI-I), the Clinical Global Impressions Severity of Illness score (CGI-S), and the Sheehan Disability Scale (SDS). Safety and tolerability assessments were also performed at regular intervals. Subjects treated with fluvoxamine CR had a numerically greater decrease in LSAS total scores than subjects treated with placebo at endpoint. Analysis of data from baseline (day 1) to endpoint (last observation carried forward) demonstrated that this difference tended towards significance, while severity of illness on the CGI-S and disability on the SDS were significantly lower in the fluvoxamine CR group than in the placebo group. The same trends were observed when only data from weeks 12–24 were included in the analysis; although the magnitude of changes was smaller in the extension phase than in the acute phase, fluvoxamine CR-treated subjects continued to show improvement compared to placebo-treated subjects. Most treatment-emergent signs and symptoms (TESS) were mild to moderate in severity. No unexpected abnormalities were reported on vital signs, electrocardiagrams, or laboratory investigations. These data support the long-term efficacy, safety, and tolerability of fluvoxamine CR in the treatment of GSAD. Given the prevalence, persistence, and disability associated with GSAD, and the relative paucity of long-term treatment studies of SAD, the current dataset provides empirical support for the current clinical consensus that pharmacotherapy of this disorder should be continued beyond the acute phase.

(Received August 26 2002)
(Reviewed December 4 2002)
(Revised May 14 2003)
(Accepted May 21 2003)

Key Words: Fluvoxamine; fluvoxamine CR; maintenance treatment; selective serotonin reuptake inhibitor; social anxiety disorder; social phobia.

c1 Professor D. J. Stein, P.O. Box 19063, Tygerberg 7505, Cape Town, South Africa. E-mail: