D-cycloserine augmentation of behavioral therapy for the treatment of anxiety disorders: a meta-analysis

Objective: To determine the efficacy of D-cycloserine augmentation of behavioral therapy for the treatment of anxiety disorders.

Data sources and study selection: Using the search terms D-cycloserine AND anxiety disorders (MeSH), PubMed (1965-June 2011), PsycINFO, and Scopus were searched for randomized, double-blind, placebo-controlled trials of D-cycloserine augmentation of behavioral therapy for the treatment of anxiety disorders. Anxiety disorders were defined as any disorder categorized as such in DSM-IV-TR.

Data extraction: A random-effects model was used to calculate the standardized mean difference of change in anxiety rating scale scores with D-cycloserine augmentation compared to placebo, which was the primary outcome measure. Subgroup analysis and meta-regression were used to examine the effects of D-cycloserine dosage and timing (relative to exposure therapy), diagnostic indication, number of therapy sessions, and trial methodological quality on D-cycloserine efficacy.

Results: Meta-analysis of 9 trials involving 273 subjects demonstrated a significant benefit from D-cycloserine augmentation (standardized mean difference = 0.46 [95% CI, 0.15 to 0.77], z = 2.89, P = .004). There was no evidence of publication bias, but a moderate, nonsignificant degree of heterogeneity between trials (I2 = 36%, Q = 12.6, df = 8, P = .12) was found. Secondary analyses yielded no significant findings.

Conclusions: D-Cycloserine appears to be an effective augmentation agent that enhances the effects of behavioral therapy in the treatment of anxiety disorders. In contrast to a previous meta-analysis that examined D-cycloserine's effects in both animals and humans, we found no evidence of an effect of dose number, dose timing, or dosage of D-cycloserine on reported efficacy in the ranges studied.