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.

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.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Antidepressive Agents / administration & dosage
  • Antidepressive Agents / adverse effects
  • Antidepressive Agents / therapeutic use
  • Citalopram / administration & dosage*
  • Citalopram / therapeutic use
  • Creatine / administration & dosage*
  • Creatine / adverse effects
  • Creatine / therapeutic use
  • Depressive Disorder, Major / drug therapy*
  • Double-Blind Method
  • Drug Therapy, Combination / methods
  • Drug Therapy, Combination / psychology*
  • Female
  • Humans
  • Middle Aged
  • Serotonin Uptake Inhibitors / administration & dosage
  • Serotonin Uptake Inhibitors / therapeutic use*
  • Women's Health*

Substances

  • Antidepressive Agents
  • Serotonin Uptake Inhibitors
  • Citalopram
  • Creatine

Associated data

  • ClinicalTrials.gov/NCT00729755