Lack of efficacy of 5 grams daily of creatine in schizophrenia: a randomized, double-blind, placebo-controlled trial.
OBJECTIVE
Creatine plays a pivotal role in brain energy homeostasis and has been tried in the treatment of neurologic, neuromuscular, and atherosclerotic disease with a paucity of side effects. Creatine monohydrate supplementation may enhance cognitive functions in healthy subjects. Several independent lines of evidence suggest the possible involvement of altered cerebral energy metabolism in schizophrenia. Creatine effects on brain energy metabolism and its possible cognitive-enhancing properties raise the possibility of developing a new therapeutic strategy in schizophrenia by focusing on treating metabolic hypoactive brain areas including frontal regions.


METHODS
Twelve schizophrenia patients (DSM-IV criteria) were enrolled into a treatment study with creatine or placebo, and each treatment was administered for 3 months (dosage, 3-5 grams per day) in a randomized, double-blind crossover design. Ten patients completed the study, which was conducted from November 2004 through February 2006. Rating scales included the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impressions (CGI) scale, scales for the assessment of side effects, and a cognitive battery.


RESULTS
Creatine treatment was not superior to placebo in improving the scores of PANSS, CGI, or the neurocognitive measures administered. Side effects of creatine treatment were few.


CONCLUSIONS
Three months of creatine administration failed to detect any efficacy in treating symptoms of schizophrenia, but further research is suggested.


BACKGROUND
ClinicalTrials.gov identifier NCT00140192.
Kaptsan
Alex
A
Faculty of Health Sciences, Department of Psychiatry, Ben Gurion University of the Negev and the Beersheva Mental Health Center, Beersheva, Israel.
Odessky
Alex
A
Osher
Yamima
Y
Levine
Joseph
J
D000328:Adult; D003071:Cognition / Q000187:drug effects; D003401:Creatine / Q000009:adverse effects / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000188:drug therapy*; D016896:Treatment Outcome
D003401:Creatine