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

• DOI: 10.1176/appi.ajp.2012.12010009
• Publication Date: 2012-09-05T23:00:36Z
• Authors: In Kyoon Lyoo; Sujung Yoon; Tae-Suk Kim; Jaeuk Hwang; Jieun E. Kim; Wangyoun Won; Sujin Bae; Perry F. Renshaw
• Keywords: Adult; Depressive Disorder, Major; Administration, Oral; Citalopram; Middle Aged; Creatine; Antidepressive Agents; 3. Good health; 03 medical and health sciences; 0302 clinical medicine; Double-Blind Method; Humans; Women's Health; Drug Therapy, Combination; Female; Selective Serotonin Reuptake Inhibitors; Aged

Antidepressants targeting monoaminergic neurotransmitter systems, despite their immediate effects at the synaptic level, usually require several weeks of administration to achieve clinical efficacy. The authors propose a strategy of adding creatine monohydrate (creatine) to a selective serotonin reuptake inhibitor (SSRI) in the treatment of patients with major depressive disorder. Such augmentation may lead to a more rapid onset of antidepressant effects and a greater treatment response, potentially by restoring brain bioenergetics at the cellular level.Fifty-two women with major depressive disorder were enrolled in an 8-week double-blind placebo-controlled clinical trial and randomly assigned to receive escitalopram in addition to either creatine (5 g/day, N=25) or placebo (N=27). Efficacy was primarily assessed by changes in the Hamilton Depression Rating Scale (HAM-D) score.In comparison to the placebo augmentation group, patients receiving creatine augmentation showed significantly greater improvements in HAM-D score, as early as week 2 of treatment. This differential improvement favoring creatine was maintained at weeks 4 and 8. There were no differences between treatment groups in the proportion of patients who discontinued treatment prematurely (creatine: N=8, 32.0%; placebo: N=5, 18.5%) or in the overall frequency of all reported adverse events (creatine: 36 events; placebo: 45 events).The current study suggests that creatine augmentation of SSRI treatment may be a promising therapeutic approach that exhibits more rapid and efficacious responses in women with major depressive disorder.