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Randomized Controlled Trial
. 2012 Sep;169(9):937-945.
doi: 10.1176/appi.ajp.2012.12010009.

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

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Free PMC article
Randomized Controlled Trial

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

In Kyoon Lyoo et al. Am J Psychiatry. .
Free PMC article

Abstract

Objective: 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.

Method: 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.

Results: 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).

Conclusions: 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.

Trial registration: ClinicalTrials.gov NCT00729755.

Figures

FIGURE 1
FIGURE 1
Screening, Randomization, and Disposition of Women With Major Depressive Disorder Randomly Assigned to Creatine Monohydrate or Placebo Augmentation of SSRI
FIGURE 2
FIGURE 2
Percentage Change in Hamilton Depression Rating Scale (HAM-D) Score for Women With Major Depressive Disorder Assigned to Creatine Monohydrate or Placebo Augmentation of SSRIa

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