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Am J Psychiatry. 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.

Author information

1
Department of Psychiatry and the Interdisciplinary Program in Neuroscience, Seoul National University College of Medicine and College of Natural Sciences, Seoul, South Korea; the Department of Psychiatry, Catholic University of Korea College of Medicine, Seoul, South Korea; the Brain Institute and the Department of Psychiatry, University of Utah, Salt Lake City; the Department of Psychiatry, Soonchunhyang University College of Medicine, Seoul, South Korea; and the Department of Brain and Cognitive Sciences, Ewha Women's University Graduate School, Seoul, South Korea.
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Contributed equally

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.

PMID:
22864465
PMCID:
PMC4624319
DOI:
10.1176/appi.ajp.2012.12010009
[Indexed for MEDLINE]
Free PMC Article

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