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. METHOD: 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. CONCLUSION: Three months of creatine administration failed to detect any efficacy in treating symptoms of schizophrenia, but further research is suggested. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov identifier NCT00140192.

Right prefrontal TMS versus sham treatment of mania: a controlled study.

OBJECTIVE: Left prefrontal transcranial magnetic stimulation (TMS) has been reported to have ECT-like effects in depression and we therefore planned a study of TMS in mania. Sixteen patients completed trial of right versus left prefrontal TMS at 20 Hz, 2-sec duration per train, 20 trains per day for 10 treatment days. Mania was evaluated using the Mania Scale, the Brief Psychiatric Rating Scale and the Clinical Global Impression. Significantly more improvement was observed in patients treated with right prefrontal TMS than with left prefrontal. We now report a follow-up study of right active TMS versus right sham TMS with the same indications and parameters. METHODS: Twenty-five patients entered and 19 completed right TMS versus sham right TMS. RESULTS: Right TMS was no more effective than sham TMS. CONCLUSIONS: It is possible that the previous results were due to an effect of left TMS to worsen mania. Alternatively, it is noted that the present patient group had much more psychosis than the previous study of TMS in mania, and depression studies have reported that psychosis is a poor prognostic sign for TMS response.