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A pilot dose-finding clinical trial of creatine monohydrate augmentation to SSRIs/SNRIs/NASA antidepressant treatment in major depression

Nemets, Boris; Levine, Joseph

International Clinical Psychopharmacology: May 2013 - Volume 28 - Issue 3 - p 127–133
doi: 10.1097/YIC.0b013e32835ff20f

Creatine’s effects on brain energy metabolism raise the possibility of developing a new therapeutic strategy in depression focusing on the treatment of metabolic hypoactive brain areas. Previous creatine augmentation studies in patients with major depression showed a beneficial effect. Eighteen patients (14 women) with major depression not responding to previous 3 weeks of antidepressant treatment were enrolled into a pilot, dose finding, 4-week double-blind parallel augmentation study where creatine monohydrate 5 or 10 g daily or placebo was added to ongoing SSRIs/SNRIs/NASA treatment. Rating scales included the Hamilton Depression Rating Scale and the Clinical Global Impression Severity scale. Overall, there was no difference between creatine administered at 5 or 10 g daily and its corresponding placebos. Two female patients on creatine augmentation, but none on the placebo, showed early improvement of more than 50% reduction in Hamilton Depression Rating Scale after 2 weeks of creatine treatment. No clinically relevant side effects were reported. This preliminary study seems to suggest that the strategy using creatine augmentation in major depressive women showing no ‘real-life response’ to 3 weeks of treatment with SSRIs/SNRIs/NASA treatment is of no advantage compared with placebo. However, such creatine augmentation may still induce a more rapid response in a small subgroup of these female patients.

Psychiatric Department, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel

Correspondence to Joseph Levine, MD, Beer-Sheva Mental Health Center, PO Box 4600, Beer-Sheva 84170, Israel Tel: +972 54 476 1901; fax: +972 8 640 1621; e-mail:

Received August 21, 2012

Accepted February 7, 2013

© 2013 Lippincott Williams & Wilkins, Inc.