A Meta-Analysis of d-Cycloserine in Exposure-Based Treatment: Moderators of Treatment Efficacy, Response, and Diagnostic Remission

Objective: This meta-analysis examined treatment efficacy, treatment response, and diagnostic remission effect sizes and moderators of d-cycloserine-augmented exposure treatment in randomized controlled trials (RCTs) of individuals with anxiety disorders, obsessive-compulsive disorder (OCD), and posttraumatic stress disorder (PTSD).

Data Sources and Study Selection: The terms D-cycloserine AND randomized controlled trial were used to search the PubMed (1965-May 2015), PsycINFO, and Scopus databases for randomized placebo-controlled trials of d-cycloserine-augmented exposure therapy for anxiety disorders, OCD, and PTSD.

Data Extraction: Clinical variables and effect sizes were extracted from 20 RCTs (957 participants). A random-effects model calculated the effect sizes for treatment efficacy, treatment response, and diagnostic remission using standardized rating scales. Subgroup analyses and meta-regression were used to examine potential moderators.

Results: A small, nonsignificant benefit of d-cycloserine augmentation compared to placebo augmentation was identified across treatment efficacy (g = 0.15), response (risk ratio [RR] = 1.08), and remission (RR = 1.109), with a moderately significant effect (P = .03) for anxiety disorders specifically (g = 0.33). At initial follow-up assessments, a small, nonsignificant effect size of d-cycloserine augmentation compared to placebo was found for treatment efficacy (g = 0.21), response (RR = 1.06), and remission (RR = 1.12). Specific treatment moderators (eg, comorbidity, medication status, gender, publication year) were found across conditions for both acute treatment and initial follow-up assessments.

Conclusions: d-Cycloserine does not universally enhance treatment outcomes but demonstrates promise for anxiety disorders. Distinct treatment moderators may account for discrepant findings across RCTs and disorders. Future trials may be strengthened by accounting for identified moderators in their design, with ongoing research needed on the mechanisms of d-cycloserine to tailor treatment protocols and maximize its benefit.