The International Journal of Neuropsychopharmacology

Brief Report

Pilot controlled trial of d-serine for the treatment of post-traumatic stress disorder

Uriel Heresco-Levya1a2 c1, Agnes Vassa1a2, Boaz Blocha3, Herman Woloskera4, Elena Dumina4, Livia Balana4, Lisa Deutscha1 and Ilana Kremera3

a1 Psychiatry and Research Departments, Ezrath Nashim-Herzog Memorial Hospital, Jerusalem, Israel

a2 Psychiatry Department, Hadassah Medical School, Hebrew University, Jerusalem, Israel

a3 Psychiatry and Research Departments, Haemek Medical Center and B. Rappaport Faculty of Medicine, Technion – Israel Institute of Technology, Haifa, Israel

a4 Department of Biochemistry, B. Rappaport Faculty of Medicine, Technion – Israel Institute of Technology, Haifa, Israel


Enhancement of neurotransmission mediated at N-methyl-d-aspartate subtype of glutamate receptors (NMDAR) may be beneficial in post-traumatic stress disorder (PTSD). d-serine (DSR) is an endogenous full agonist at the NMDAR-associated glycine modulatory site. Twenty-two chronic PTSD outpatients were randomly assigned to participate in a 6-wk double-blind, placebo-controlled, crossover trial with 30 mg/kg.d DSR used as monotherapy or add-on pharmacotherapy. Outcome was assessed using the Clinician-Administered PTSD scale (CAPS), Hamilton Anxiety (HAMA) and Depression (HAMD) scales and the civilian version of the Mississippi Scale for Combat-Related PTSD (MISS). DSR treatment was well tolerated and resulted in significantly (p=0.03) increased DSR serum levels. Compared with placebo administration, DSR treatment resulted in significantly reduced HAMA (p=0.007) and MISS (p=0.001) scores and a trend (p=0.07) towards improved CAPS total scores. These preliminary findings indicate that NMDAR glycine site-based pharmacotherapy may be effective in PTSD and warrant larger-sized clinical trials with optimized DSR dosages.

(Received September 22 2008)

(Reviewed December 23 2008)

(Revised January 12 2009)

(Accepted March 06 2009)

(Online publication April 15 2009)


c1 Address for correspondence: Professor U. Heresco-Levy, Ezrath Nashim-Herzog Memorial Hospital, PO Box 3900, Jerusalem, Israel 91035. Tel.: 972-2-5316906 Fax: 972-2-6536075 Email: