Effect of D-Cycloserine on Treatment of Social Phobia

Social phobia afflicts between 3%-15% of the US population. As such, it is a particularly common debilitating psychiatric disorder. Like many anxiety disorders, social phobia typically arises during adolescence. Treatment has consisted of medication or cognitive behavioral therapy (CBT). Selective Serotonin Reuptake Inhibitors (SSRIs) represent the first-line pharmacological treatment both in adults as well as adolescents (APA Treatment Guidelines 2004). Similarly, CBT significantly improves outcome in both age groups. This treatment consists of psychoeducation, exposure therapy, and cognitive restructuring. While both treatments produce clinically meaningful benefits, most patients exhibiting positive responses to these treatments continue to exhibit marked residual symptoms, if not full-blown anxiety disorders. Thus, there is great need for treatment advances.

Intense fear of social scrutiny represents a core component of social phobia, and extinction of this fear represents the goal of exposure therapy during CBT (Cohn and Hope). Finding treatments that facilitate extinction is of paramount importance. In animals, extinction involves an active learning process that is blocked by glutamatergic NMDA antagonists and facilitated by NMDA agonists. Specifically, administration of D-cycloserine (DCS), a partial agonist at the glycine modulatory site on the NMDA receptor, produces a dose-dependent facilitation of extinction in the rat. As such, DCS might facilitate extinction during exposure-based CBT. Indeed, Ressler (Ressler et al 2004) recently reported preliminary data from a clinical trial supporting this hypothesis.

We will examine the degree to which DCS treatment can augment the clinical response in social phobia to CBT-exposure-based therapy. Specifically, we will study two groups of individuals with social phobia, both of whom will receive CBT. One group will receive placebo; a second group will receive 50 mg of D-cycloserine 1-2 hours before each exposure therapy session. We hypothesize that compared to placebo, DCS will produce greater reductions in social anxiety symptoms following CBT treatment. Finally, given that chronic social anxiety disorder virtually always begins during childhood, it is particularly vital to develop early interventions for the disorder. Accordingly, our trial will examine both adolescents and adults with the disorder.