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

Abstract

ObjectiveThe 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.MethodA 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.ResultsWhile 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.ConclusionsThese 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.

Do adjuvant interventions improve treatment outcome in adult patients with posttraumatic stress disorder receiving trauma-focused psychotherapy? A systematic review

“…Given that three out of four reviewed studies did not report an overall effect for DCS, the current evidence does not support the assumption that DCS augments TF-PT. This conclusion is in line with a recent meta-analysis, including both samples of adults and children with PTSD (Bürkner, Bittner, Holling, Buhlmann, & Hashimoto, 2017). The reviewed trials on methylene blue, oxytocin and yohimbine also did not detect significant adjuvant treatment effects.…”

Effect of D-Cycloserine on the Effect of Concentrated Exposure and Response Prevention in Difficult-to-Treat Obsessive-Compulsive Disorder

“…There was a significant main effect of time (χ 2 3 = 776.26; P < .001). The reduction in Y-BOCS score from pretreatment to posttreatment was significant for all treatment groups (placebo, - 13 revealed no statistically significant differences on Y-BOCS score between the placebo group and the 2 DCS groups combined (posttreatment, χ 2 1 = 3.21; P = .07; 12-month follow-up, χ 2 1 = 0.07; P = .79). Patients with a history of nonresponse increased their Y-BOCS scores from posttreatment to the follow-up period (eFigure 3 in Supplement 2).…”

Impaired discriminative fear conditioning during later training trials differentiates generalized anxiety disorder, but not panic disorder, from healthy control participants

“…For example, d-cycloserine, a partial agonist at the N -methyl-D-aspartate receptor, has been shown to enhance discrimination learning in rats [53] and improve outcomes from fear extinction treatments (e.g., exposure) in humans [54,55]. That said, there is mixed evidence for the effectiveness of d-cycloserine when used to augment treatment for those with anxiety disorders [56,57], and it has been suggested that the dosage and timing of d-cycloserine should be tailored to the specific type of psychotherapeutic treatment used [54]. An intriguing, (although given current results, speculative) future direction is to investigate how d-cycloserine might be used in conjunction with exposure protocols that incorporate discrimination training to improve treatment for GAD, especially for patients who show minimal gains in response to more traditional exposure interventions.…”