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.

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