The International Journal of Neuropsychopharmacology

Brief Report

Pilot-controlled trial of D-cycloserine for the treatment of post-traumatic stress disorder

Uriel Heresco-Levy a1c1, Ilana Kremer a2, Daniel C. Javitt a3, Rodica Goichman a2, Alon Reshef a2, Monica Blanaru a2 and Tamar Cohen a2
a1 Ezrath Nashim-Herzog Memorial Hospital, and Department of Psychiatry, Hadassah Medical School–Hebrew University, Jerusalem, Israel
a2 Psychiatry Department, Haemek Medical Center, Afula, and Faculty of Medicine, Technion, Haifa, Israel
a3 Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY, and Department of Psychiatry, New York University, NY, USA


Dysfunction of glutamatergic neurotransmission may be relevant to the pathogenesis of post-traumatic stress disorder (PTSD). Preclinical and clinical evidence suggests that PTSD symptoms could be alleviated following enhancement of neurotransmission mediated at the N-methyl-D-aspartate (NMDA) subtype of glutamate receptors. Eleven patients with chronic PTSD participated in a double-blind, placebo-controlled, cross-over trial with 50 mg/d D-cycloserine which acts as a partial agonist at the glycine regulatory site on the NMDA receptor. D-cycloserine treatment resulted in significant improvements in numbing, avoidance, and anxiety symptoms; however, similar effects were also observed during placebo treatment. In addition, D-cycloserine treatment resulted in a significant (p=0.03), reduction in the perseverative error scores as measured by the Wisconsin Card Sorting Test. This pilot study is the first to assess the efficacy of a NMDA receptor modulator for PTSD treatment and its results warrant further, larger-scale investigation.

(Received October 8 2001)
(Reviewed January 27 2002)
(Revised July 8 2002)
(Accepted July 10 2002)

Key Words: D-cycloserine; N-methyl-D-aspartate receptor; post-traumatic stress disorder.

c1 Address for correspondence: Dr U. Heresco-Levy, Psychiatry Division, Ezrath Nashim-Herzog Memorial Hospital, PO Box 35300, Jerusalem 91351, Israel. Tel.: +972-2-5316-906 Fax: +972-2-6536-075 E-mail: