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Stefan G. Hofmann, PhD; Alicia E. Meuret, PhD; Jasper A. J. Smits, PhD; Naomi M. Simon, MD, MSc; Mark H. Pollack, MD; Katherine Eisenmenger, MD; Michael Shiekh, MD; Michael W. Otto, PhD

Arch Gen Psychiatry. 2006;63:298-304.

Context  Social anxiety disorder (SAD) is common and debilitating. Although exposure therapy is one of the most effective forms of psychotherapy for this disorder, many patients remain symptomatic. Fear reduction in exposure therapy is similar to extinction learning, and early clinical data with specific phobias suggest that the treatment effects of exposure therapy for SAD may be enhanced with D-cycloserine, an agonist at the glutamatergic N-methyl-D-aspartate receptor.

Objective  To determine whether short-term treatment with 50 mg of D-cycloserine enhances the efficacy of exposure therapy for SAD.

Design  Randomized, double-blind, placebo-controlled augmentation trial examining the combination of D-cycloserine or pill placebo with exposure therapy for SAD.

Setting  Patients were self-referred from the general community to 1 of 3 research clinics.

Participants  Twenty-seven participants meeting DSM-IV criteria for SAD with significant public speaking anxiety.

Interventions  Following a diagnostic interview and pretreatment assessment, participants received 5 therapy sessions delivered in either an individual or group therapy format. The first session provided an introduction to the treatment model and was followed by 4 sessions emphasizing exposure to increasingly challenging public speech situations with videotaped feedback of performances. One hour prior to each session, participants received single doses of D-cycloserine or placebo.

Main Outcome Measures  Symptoms were assessed by patient self-report and by clinicians blind to the randomization condition before treatment, after treatment, and 1 month after the last session.

Results  Participants receiving D-cycloserine in addition to exposure therapy reported significantly less social anxiety compared with patients receiving exposure therapy plus placebo. Controlled effect sizes were in the medium to large range.

Conclusion  The pilot data provide preliminary support for the use of short-term dosing of D-cycloserine as an adjunctive intervention to exposure therapy for SAD.

Author Affiliations: Department of Psychology and Center for Anxiety and Related Disorders, Boston University (Drs Hofmann, Meuret, Eisenmenger, and Otto) and Department of Psychiatry, Harvard Medical School and Massachusetts General Hospital (Drs Simon, Pollack, and Otto), Boston; and Department of Psychology, Southern Methodist University, Dallas, Tex (Drs Smits and Shiekh).

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