D-alanine added to antipsychotics for the treatment of schizophrenia.
BACKGROUND
Hypofunction of the N-methyl-d-aspartate (NMDA) subtype glutamate receptor had been implicated in the pathophysiology of schizophrenia. Treatment with D-serine, glycine, endogenous full agonists of the glycine site of the NMDA receptor (NMDA-glycine site), D-cycloserine, a partial agonist, or sarcosine, a glycine transporter-1 inhibitor, improves the symptoms of schizophrenia. D-alanine is another endogenous agonist of the NMDA-glycine site that might have beneficial effects on schizophrenia.


METHODS
Thirty-two schizophrenic patients enrolled in a 6-week double-blind, placebo-controlled trial of D-alanine (100 mg/kg/day), which was added to their stable antipsychotic regimens. Measures of clinical efficacy and side effects were determined every other week.


RESULTS
Patint who received D-alanine treatment revealed significant reductions in their Clinical Global Impression Scale and Positive and Negative Syndrome Scale (PANSS) total scores. The Scale for the Assessment of Negative Symptoms and PANSS subscores of positive and cognitive symptoms were improved. D-alanine was well tolerated, and no significant side effect was noted.


CONCLUSIONS
The significant improvement with the D-alanine further supports the hypothesis of hypofunction of NMDA neurotransmission in schizophrenia and strengthens the proof of the principle that NMDA-enhancing treatment is a promising approach for the pharmacotherapy of schizophrenia.
Tsai
Guochuan E
GE
Department of Psychiatry, Harbor-UCLA Medical Center, Torrance, California 90509, USA. etsai@labiomed.org
Yang
Pinchen
P
Chang
Yue-Cune
YC
Chong
Mian-Yoon
MY
D000328:Adult; D000409:Alanine / Q000627:therapeutic use*; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D004311:Double-Blind Method; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D009483:Neuropsychological Tests; D011569:Psychiatric Status Rating Scales; D018009:Receptors, Glycine / Q000819:agonists*; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists*; D012559:Schizophrenia / Q000175:diagnosis / Q000188:drug therapy*; D012565:Schizophrenic Psychology; D016896:Treatment Outcome
D014150:Antipsychotic Agents; D018009:Receptors, Glycine; D016194:Receptors, N-Methyl-D-Aspartate; D000409:Alanine