Augmentation of exposure therapy with D-cycloserine for social anxiety disorder.
Hofmann SG, Meuret AE, Smits JA, Simon NM, Pollack MH, et al.;
Commented by , 22 Mar 2006
A substantial proportion of patients with Social Anxiety Disorder (SAD) remain symptomatic after treatment with either pharmacotherapy or/and cognitive behavioural therapy (CBT), indicating a clear need for more efficient treatment methods.
Aims of the study
To investigate whether short-term treatment with 50 mg of D-cycloserine (DCS) facilitates extinction of fear in patients who are treated with behavioural exposure therapy for SAD.
In a double-blind, randomised placebo-controlled study, 27 patients with SAD received 5 sessions of individual or group CBT including exposure procedures during sessions 2 to 5. In addition, patients were administered either 50 mg of DCS or pill placebo 1 hour prior to the exposure procedures. Patients were scheduled for sessions 1 week apart.
Outcome measures included the Social Phobia and Anxiety Inventory (SPAI), the Liebowitz Social Anxiety Scale (LSAS) and the Clinical Global Impression Scale severity subscale (CGI-S). Patients were assessed before treatment, after treatment, and 1 month after the last session.
At post-treatment, patients receiving DCS prior to exposure therapy reported significantly less social anxiety on the SPAI and LSAS compared with patients receiving exposure therapy plus placebo. The difference in improvement was maintained at follow-up after 1 month. The between-group differences in improvements in the CGI-scores were not statistically significant.
Professor Pull's comments
Social Anxiety Disorder (SAD) is a highly prevalent psychiatric disorder (life-time prevalence: 13.3). If untreated, the disorder usually follows a chronic course and leads to substantial impairment in vocational and social functioning.
Numerous trials have demonstrated efficacy for pharmacotherapy with several selective serotinine reuptake inhibitors as well as for CBT, but improvement with either pharmacotherapy or psychotherapy has remained partial or moderate. Treatment combining CBT and pharmacotherapy has not been found significantly superior to treatment with one or the other monotherapy.
In both humans and animals, repeated exposure to a feared stimulus, in the absence of adverse consequences, leads to a reduction of fear of this same stimulus. The reduction of fear following repeated exposure is known as fear extinction. CBT relies on exposure procedures to obtain fear extinction in anxiety disorders, in particular in specific phobias, agoraphobia and SAD.
Results of recent animal studies (ref. 1) suggest that DCS may improve NMDA synaptic transmission and facilitate extinction of fear in rats. According to a recent study by Ressler et al. (ref. 2), DCS may play a similar role in the extinction of fear in humans. Two sessions of exposure therapy in combination with DCS were sufficient to produce extinction of fear in patients with acrophobia. To obtain a similar result without DCS, at least three times more sessions of exposure therapy were necessary.
The present study gives further support to the hypothesis that cognitive enhancers, such as DCS, may indeed accelerate or facilitate fear extinction following repeated exposure.
Provided that the results of the study can be replicated, using cognitive enhancers such as DCS prior to exposure–based CBT may prove a novel therapeutic strategy to facilitate extinction of fear in SAD as well as in other phobic disorders. The new strategy may significantly reduce the duration of psychotherapy, and, consequently, contribute to reduce the costs of treatment in these disorders.
1. Walker DL, Ressler KJ, Lu KT and Davis M. Facilitation of conditioned fear extinction by systemic administration or intra-amygdala infusions of D-cycloserine as assessed with fear-potentiated startle in rats. Journal of Neurosciences 2002; 22 (6); 2343-2351 (Free full text article)
2. Ressler KJ, Rothbaum BO, Tannenbaum L, Anderson P, et al. Cognitive enhancers as adjuncts to psychotherapy: use of D-cycloserine in phobic individuals to facilitate extinction of fear. Archives of General Psychiatry 2004; 61 (11); 1136-1144 (Free full text article)