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Objective  The present meta-analysis investigates whether the antibiotic D-cycloserine (DCS), a partial agonist at the glutamatergic N-methyl-D-aspartate receptor, can augment the effect of behavior therapy in humans with anxiety and obsessive-compulsive disorders.    Method  A keyword-based computer search was conducted using common electronic databases. Only studies investigating the effect of DCS in humans with anxiety and obsessive-compulsive disorders were included, resulting in 23 studies with a combined sample size of 1314 patients. Effect sizes were coded as Hedges’ g and SMCC, the latter also incorporating differences in pre-treatment values. Bayesian multilevel meta-analysis was applied to take dependencies of effect sizes obtained from the same study into account.    Results  While previous meta-analyses found small to moderate improvements, the current results including the most recent research indicate that the overall effect of DCS is very small and almost indistinguishable from zero ( g  = -0.12,  CI  = [-0.27, 0.02];  SMCC  = -0.10,  CI  = [-0.29, 0.07]). Slightly larger effects were found for social anxious patients. Further, study quality and year of publication were relevant moderators, with higher quality / more recent studies reported smaller effects of DCS.    Conclusions  These findings raise the question of the usefulness of DCS as an augmentation of exposure therapy for anxiety and obsessive-compulsive disorders. At least, it seems to be less promising than initially thought. The fact that study quality was inversely related to the reported effect sizes underlines the importance of high quality primary research in order to avoid over-estimation of treatment effects in clinical psychology.

D-cycloserine augmentation of behavior therapy for anxiety and obsessive-compulsive disorders: A meta-analysis