Pilot controlled trial of D-serine for the treatment of post-traumatic stress disorder.
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 x 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.
Psychiatry and Research Departments, Ezrath Nashim-Herzog Memorial Hospital, Jerusalem, Israel. heresco@md.huji.ac.il
Uriel
U
Heresco-Levy
Agnes
A
Vass
Boaz
B
Bloch
Herman
H
Wolosker
Elena
E
Dumin
Livia
L
Balan
Lisa
L
Deutsch
Ilana
I
Kremer
D000328:Adult; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D018690:Excitatory Amino Acid Agonists / Q000097:blood / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011569:Psychiatric Status Rating Scales; D011619:Psychotropic Drugs / Q000097:blood / Q000627:therapeutic use*; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists*; D012694:Serine / Q000097:blood / Q000627:therapeutic use*; D013313:Stress Disorders, Post-Traumatic / Q000188:drug therapy* / Q000378:metabolism / Q000523:psychology; D016896:Treatment Outcome
D018690:Excitatory Amino Acid Agonists; D011619:Psychotropic Drugs; D016194:Receptors, N-Methyl-D-Aspartate; D012694:Serine