Effects of Creatine Monohydrate Augmentation on Brain Metabolic and Network Outcome Measures in Women With Major Depressive Disorder

Sujung Yoon, Jieun E. Kim, Jaeuk Hwang, Tae Suk Kim, Hee Jin Kang, Eun Namgung, Soonhyun Ban, Subin Oh, Jeongwon Yang, Perry F. Renshaw, In Kyoon Lyoo

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

Background Creatine monohydrate (creatine) augmentation has the potential to accelerate the clinical responses to and enhance the overall efficacy of selective serotonin reuptake inhibitor treatment in women with major depressive disorder (MDD). Although it has been suggested that creatine augmentation may involve the restoration of brain energy metabolism, the mechanisms underlying its antidepressant efficacy are unknown. Methods In a randomized, double-blind, placebo-controlled trial, 52 women with MDD were assigned to receive either creatine augmentation or placebo augmentation of escitalopram; 34 subjects participated in multimodal neuroimaging assessments at baseline and week 8. Age-matched healthy women (n = 39) were also assessed twice at the same intervals. Metabolic and network outcomes were measured for changes in prefrontal N-acetylaspartate and changes in rich club hub connections of the structural brain network using proton magnetic resonance spectroscopy and diffusion tensor imaging, respectively. Results We found MDD-related metabolic and network dysfunction at baseline. Improvement in depressive symptoms was greater in patients receiving creatine augmentation relative to placebo augmentation. After 8 weeks of treatment, prefrontal N-acetylaspartate levels increased significantly in the creatine augmentation group compared with the placebo augmentation group. Increment in rich club hub connections was also greater in the creatine augmentation group than in the placebo augmentation group. Conclusions N-acetylaspartate levels and rich club connections increased after creatine augmentation of selective serotonin reuptake inhibitor treatment. Effects of creatine administration on brain energy metabolism and network organization may partly underlie its efficacy in treating women with MDD.

Original languageEnglish
Pages (from-to)439-447
Number of pages9
JournalBiological Psychiatry
Volume80
Issue number6
DOIs
StatePublished - 15 Sep 2016

Bibliographical note

Publisher Copyright:
© 2016 Society of Biological Psychiatry

Keywords

  • Antidepressant
  • Brain bioenergetics
  • Creatine monohydrate
  • Major depressive disorder
  • Network organization
  • Selective serotonin reuptake inhibitor

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