Creatine Augmentation Treatment in Major Depressive Disorder Subjects

Given 1) the established safety with short-term or long-term supplementation of Cr, 2) its potential usefulness in improving brain energy metabolism, 3) the reported abnormality in brain energy metabolism in MDD subjects, and 4) plausible association between depression and inflammatory mediators, we hypothesize that oral Cr augmentation will help reduce symptoms in MDD patients as well as normalize a deficit in brain energy metabolism and that improvement of MDD and brain energy metabolism will be correlated with inflammatory mediators changes. In this study, we plan to conduct an randomized, double-blind, placebo-controlled augmentation study with creatine in addition to escitalopram. We will assess the efficacy and safety of the Cr augmentation and evaluate changes relevant to brain energy metabolism and inflammatory mediators.

In addition to 10-20mg escitalopram, the subjects will be given total 3 gram of creatine (500mg/capsule) a day in first week and then, 5 gram a day in the rest of the weeks.

In addition to 10-20mg escitalopram, the subjects will be given total 6 capsules of placebo (equal quantities to those of creatine group) a day in first week and then, 10 capsules a day in the rest of the weeks.

Inclusion Criteria: 19-65 year-old male or female Major depressive disorder diagnosed by SCID-IV Hamilton depression rating scale score >= 16 at screening Written informed consent Exclusion Criteria: Suicidal idea that needs hospitalization Any other axis I psychiatric disorder Neurologic disease (eg., epilepsy, infarct, multiple sclerosis, brain tumor) IQ below 80 Inflammatory disease including autoimmune disease Taking anti-inflammatory medication Serious physical disease Substance abuse or dependence history in recent 6 months Pregnant or having plan to be pregnant

Yoon S, Kim JE, Hwang J, Kim TS, Kang HJ, Namgung E, Ban S, Oh S, Yang J, Renshaw PF, Lyoo IK. Effects of Creatine Monohydrate Augmentation on Brain Metabolic and Network Outcome Measures in Women With Major Depressive Disorder. Biol Psychiatry. 2016 Sep 15;80(6):439-447. doi: 10.1016/j.biopsych.2015.11.027. Epub 2015 Dec 15.

Lyoo IK, Yoon S, Kim TS, Hwang J, Kim JE, Won W, Bae S, Renshaw PF. A randomized, double-blind placebo-controlled trial of oral creatine monohydrate augmentation for enhanced response to a selective serotonin reuptake inhibitor in women with major depressive disorder. Am J Psychiatry. 2012 Sep;169(9):937-945. doi: 10.1176/appi.ajp.2012.12010009.