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)