D-serine efficacy as add-on pharmacotherapy to risperidone and olanzapine for treatment-refractory schizophrenia.
BACKGROUND
D-serine, a selective full agonist at the glycine site of N-methyl-D-aspartate glutamate receptor, might presently be the compound of choice for counteracting the hypothesized dysfunction of this receptor class in schizophrenia. Studies performed with Taiwanese patients indicate that D-serine significantly improves schizophrenia symptoms when used as adjuvant to conventional neuroleptics but not to clozapine. We assessed the efficacy and safety of D-serine adjuvant treatment for Occidental schizophrenia patients treated with newer atypical antipsychotics.


METHODS
Thirty-nine risperidone- or olanzapine-treated schizophrenia patients participated in a double-blind, placebo-controlled, 6-week crossover trial with 30 mg/kg/day D-serine added to their antipsychotic medication. Measures of clinical efficacy and side effects were determined biweekly throughout the study. Clinical laboratory parameters and amino acid serum levels were monitored.


RESULTS
D-serine administration induced increased serine serum levels (p < .001) and resulted in significant (p < .001) improvements in negative, positive, cognitive, and depression symptoms, as measured by the Positive and Negative Syndrome Scale. For approximately one third of the sample, D-serine treatment resulted in significant (>20%) reductions in Brief Psychiatric Rating Scale total scores. D-serine was well tolerated, and no detrimental changes in clinical laboratory parameters were noted.


CONCLUSIONS
These findings 1) indicate that risperidone and olanzapine efficacy might be augmented with D-serine adjuvant treatment; 2) confirm D-serine efficacy against main schizophrenia symptom domains; and 3) warrant the assessment of D-serine antipsychotic monotherapy for this illness.
Heresco-Levy
Uriel
U
Ezrath Nashim-Herzog Memorial Hospital, Jerusalem, Israel; Department of Psychiatry, Hadassah Medical School, Hebrew University, Jerusalem, Israel. heresco@md.huji.ac.il
Javitt
Daniel C
DC
Ebstein
Richard
R
Vass
Agnes
A
Lichtenberg
Pesach
P
Bar
Gali
G
Catinari
Sara
S
Ermilov
Marina
M
D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000627:therapeutic use*; D001806:Blood Urea Nitrogen; D003404:Creatinine / Q000378:metabolism; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077152:Olanzapine; D010919:Placebos; D011569:Psychiatric Status Rating Scales; D018967:Risperidone / Q000627:therapeutic use*; D012559:Schizophrenia / Q000097:blood / Q000188:drug therapy*; D012694:Serine / Q000097:blood / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
D014150:Antipsychotic Agents; D010919:Placebos; D001569:Benzodiazepines; D012694:Serine; D003404:Creatinine; D018967:Risperidone; D000077152:Olanzapine