Sujung Yoon1, Jieun E Kim1, Jaeuk Hwang2, Tae-Suk Kim3, Hee Jin Kang1, Eun Namgung1, Soonhyun Ban1, Subin Oh1, Jeongwon Yang1, Perry F Renshaw4, In Kyoon Lyoo5. 1. Ewha Brain Institute and Department of Brain and Cognitive Sciences, Ewha W. University, Seoul, South Korea. 2. Department of Psychiatry, Soonchunhyang University College of Medicine, Seoul, South Korea. 3. Department of Psychiatry, The Catholic University of Korea College of Medicine, Seoul, South Korea. 4. Brain Institute and Department of Psychiatry, University of Utah, Salt Lake City, Utah. 5. Ewha Brain Institute and Department of Brain and Cognitive Sciences, Ewha W. University, Seoul, South Korea; Brain Institute and Department of Psychiatry, University of Utah, Salt Lake City, Utah. Electronic address: inkylyoo@ewha.ac.kr.
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.
RCT Entities:
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.
Authors: Kristen L Eckstrand; Michael John Travis; Erika E Forbes; Mary Louise Phillips Journal: Biol Psychiatry Date: 2016-09-19 Impact factor: 13.382
Authors: Cielo García-Montero; Miguel A Ortega; Miguel Angel Alvarez-Mon; Oscar Fraile-Martinez; Adoración Romero-Bazán; Guillermo Lahera; José Manuel Montes-Rodríguez; Rosa M Molina-Ruiz; Fernando Mora; Roberto Rodriguez-Jimenez; Javier Quintero; Melchor Álvarez-Mon Journal: Nutrients Date: 2022-03-06 Impact factor: 5.717