Creatine plays a pivotal role in brain energy homeostasis. Creatine supplementation is widely used in enhancing sports performance, and has been tried in the treatment of neurological, neuromuscular and atherosclerotic disease with a paucity of side effects.

Dechent et al (1999) studied the effect of oral creatine supplementation for 4 wk demonstrating a statistically significant increase of mean concentration of total creatine across brain regions. These findings suggest the possibility of using oral creatine supplementation to modify brain high-energy phosphate metabolism in subjects with various brain disorders, including schizophrenia and major depression. Recently, Rae et al (2003) reported that creatine supplementation for 6 weeks had a significant positive effect on both working memory and Raven matrices. Several independent lines of evidence suggest the possible involvement of altered cerebral energy metabolism in schizophrenia.

We are performing a double blind cross-over study of creatine in schizophrenia.

Forty patients will be treated with creatine for 3 months in a double-blind crossover design. Rating scales will include scales for assessing negative and positive symptoms of schizophrenia, clinical global impressions scale, scales for side–effects and a cognitive battery

Creatine effects on brain energy metabolism and its possible cognitive enhancing properties raise the possibility of developing a new therapeutic strategy in schizophrenia focusing on treating metabolic hypoactive brain areas including frontal regions.