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Creatine monohydrate in resistant depression: a preliminary study


  • The authors of this paper do not have any commercial associations that might pose a conflict of interest in connection with this manuscript.

Professor Joseph Levine, Beer Sheva Mental Health Center, PO Box 4600, Beer Sheva, Israel. Fax: +972 8 640 1621;


Objectives:  Creatine plays a pivotal role in brain energy homeostasis, and altered cerebral energy metabolism may be involved in the pathophysiology of depression. Oral creatine supplementation may modify brain high-energy phosphate metabolism in depressed subjects.

Methods:  Eight unipolar and two bipolar patients with treatment-resistant depression were treated for four weeks with 3–5 g/day of creatine monohydrate in an open add-on design. Outcome measures were the Hamilton Depression Rating Scale, Hamilton Anxiety Scale, and Clinical Global Impression scores, recorded at baseline and at weeks 1, 2, 3 and 4.

Results:  One patient improved considerably after one week and withdrew. Both bipolar patients developed hypomania/mania. For the remaining seven patients, all scale scores significantly improved. Adverse reactions were mild and transitory.

Conclusions:  This small, preliminary, open study of creatine monohydrate suggests a beneficial effect of creatine augmentation in unipolar depression, but possible precipitation of a manic switch in bipolar depression.

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