A meta-analysis of D-cycloserine and the facilitation of fear extinction and exposure therapy.
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.
Norberg
Melissa M
MM
Institute of Living, New Haven, CT 06106, USA.
Krystal
John H
JH
Tolin
David F
DF
D000818:Animals; D001008:Anxiety Disorders / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D003131:Combined Modality Therapy; D003523:Cycloserine / Q000494:pharmacology* / Q000627:therapeutic use*; D003887:Desensitization, Psychologic; D005108:Extinction, Psychological / Q000187:drug effects*; D005239:Fear / Q000187:drug effects*; D006801:Humans; D007171:Implosive Therapy; D009473:Neuronal Plasticity / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects; D016896:Treatment Outcome
D016194:Receptors, N-Methyl-D-Aspartate; D003523:Cycloserine