A Meta-Analysis of D-Cycloserine and the Facilitation of Fear Extinction and Exposure Therapy

Melissa M. Norberg, John H. Krystal, David F. Tolin*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

413 Citations (Scopus)


Background: Translational research suggests that D-cycloserine (DCS), a partial N-methyl-D-aspartate (NMDA) receptor agonist, might facilitate fear extinction and exposure therapy by either enhancing NMDA receptor function during extinction or by reducing NMDA receptor function during fear memory consolidation. This article provides a quantitative review of DCS-augmented fear extinction and exposure therapy literature. Methods: English-language journal articles that examined DCS augmented with fear extinction or exposure therapy were identified through public databases from June 1998 through September 2007, through references of originally identified articles and contact with DCS investigators. Data were extracted for study author, title, and year; trial design; type of subject (animal vs. human; clinical vs. nonclinical); sample size, DCS dose, and timing in relation to extinction/exposure procedures; dependent variable; group means and SDs at post-extinction/exposure; and follow-up outcome. Results: D-cycloserine enhances fear extinction/exposure therapy in both animals and anxiety-disordered humans. Gains generally were maintained at follow-up, although some lessening of efficacy was noted. D-cycloserine was more effective when administered a limited number of times and when given immediately before or after extinction training/exposure therapy. Conclusions: This meta-analysis suggests that DCS is a useful target for translational research on augmenting exposure-based treatment via compounds that impact neuroplasticity. D-cycloserine 's major contribution to exposure-based therapy might be to increase its speed or efficiency, because the effects of DCS seem to decrease over repeated sessions. This information might guide translational researchers in discovering more selective and/or effective agents that effectively enhance (or reduce) NMDA receptor function.

Original languageEnglish
Pages (from-to)1118-1126
Number of pages9
JournalBiological Psychiatry
Issue number12
Publication statusPublished - 15 Jun 2008
Externally publishedYes


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