D-serine added to antipsychotics for the treatment of schizophrenia.
BACKGROUND
Hypofunction of N-methyl-D-aspartate (NMDA) subtype glutamate receptor has been implicated in the pathophysiology of schizophrenia. D-serine is a full agonist of the glycine site of NMDA receptor, an endogenous cotransmitter enriched in corticolimbic regions and distributed in parallel with NMDA receptor. Supplementation of D-serine may improve the symptoms of schizophrenia.


METHODS
Thirty-one Taiwanese schizophrenic patients enrolled in a 6-week double-blind, placebo-controlled trial of D-serine (30 mg/kg/day), which was added to their stable antipsychotic regimens. Of these, 28 completed the trial. Measures of clinical efficacy, side effects, and serum levels of amino acids and D-serine were determined every other week. Wisconsin Card Sorting Test (WCST) was performed at the beginning and end of the trial.


RESULTS
Patients who received D-serine treatment revealed significant improvements in their positive, negative, and cognitive symptoms as well as some performance in WCST. D-serine levels at week 4 and 6 significantly predicted the improvements. D-serine was well tolerated and no significant side effects were noted.


CONCLUSIONS
The significant improvement with the D-serine further supports the hypothesis of NMDA receptor hypofunction in schizophrenia. Given the effects of D-serine on positive symptoms, a trial of D-serine alone in schizophrenia should be considered.
Tsai
G
G
Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston 02129, USA.
Yang
P
P
Chung
L C
LC
Lange
N
N
Coyle
J T
JT
D000328:Adult; D014150:Antipsychotic Agents / Q000494:pharmacology*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000175:diagnosis / Q000188:drug therapy*; D012694:Serine / Q000009:adverse effects*
D014150:Antipsychotic Agents; D012694:Serine