Jerome Sarris1,2, Jenifer Murphy3, Con Stough4, David Mischoulon5, Chad Bousman6,7, Patricia MacDonald8, Laura Adams8, Sonia Nazareth8, Georgina Oliver3, Lachlan Cribb3, Karen Savage3,4, Ranjit Menon3, Suneel Chamoli8, Michael Berk7,9,10,11, Chee H Ng3, Gerard J Byrne8. 1. NICM Health Research Institute, Westmead, Western Sydney University, Locked Bag 1797, Penrith, NSW, 2751, Australia. j.sarris@westernsydney.edu.au. 2. Professorial Unit, The Melbourne Clinic, Department of Psychiatry, Melbourne University, Melbourne, Australia. j.sarris@westernsydney.edu.au. 3. Professorial Unit, The Melbourne Clinic, Department of Psychiatry, Melbourne University, Melbourne, Australia. 4. Centre for Human Psychopharmacology, Swinburne University of Technology, Melbourne, Australia. 5. Depression Clinical and Research Program, Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. 6. Departments of Medical Genetics, Psychiatry, and Physiology & Pharmacology, University of Calgary, Calgary, AB, Canada. 7. Department of Psychiatry, The University of Melbourne, Parkville, Australia. 8. Faculty of Medicine, Discipline of Psychiatry, Centre for Clinical Research, Royal Brisbane & Women's Hospital, Herston, The University of Queensland, Brisbane, Australia. 9. IMPACT SRC, School of Medicine, Barwon Health, Deakin University, Geelong, Australia. 10. Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Australia. 11. Orygen, The Centre of Excellence in Youth Mental Health, The University of Melbourne, Parkville, Australia.
Abstract
RATIONALE: Dysregulation of the one carbon cycle is documented in depression. Thereby, S-adenosylmethionine (SAMe), a one-carbon cycle nutraceutical compound with a favourable side effect profile, has a theoretical rationale for efficacy. However, further controlled studies are required to confirm SAMe's efficacy. OBJECTIVES: To test the efficacy of SAMe versus placebo in unmedicated DSM-5 diagnosed (major depressive disorder) (MDD) patients with mild-to-moderate levels of depressive symptoms. METHODS: We conducted an 8-week, double-blind, randomised controlled trial testing 800 mg/day of SAMe monotherapy versus placebo in 49 patients with MDD (Montgomery-Åsberg Depression Rating Scale [MADRS] score 14-25) who were not currently taking antidepressants. One-carbon cycle biomarkers, brain-derived neurotropic factor (BDNF), and relevant single nucleotide polymorphisms (SNPs) were analysed as potential treatment moderators. RESULTS: A clinically relevant differential reduction from baseline to week 8 of 3.76 points occurred on the primary outcome (MADRS) in favour of SAMe. This however was not significant (p = 0.13) on an adjusted linear mixed model, notwithstanding a medium to large effect size of 0.72. A high placebo response rate of 53% occurred (> 50% reduction on MADRS). Exploratory analyses showed that SAMe was however effective in reducing depression amongst participants with milder depression severity (MADRS ≤ 22, p = 0.045). Response was not moderated by BDNF, SNPs, or one-carbon cycle biomarkers, although increased folate concentrations were correlated with improved symptoms in the SAMe group (r = - 0.57, p = 0.026). The treatment was safe and well tolerated. CONCLUSIONS: Although a differential reduction in depression symptoms between groups was observed in favour of SAMe, the results of this pilot study were not statistically significant. TRIAL REGISTRATION: ANZCTR-Australian New Zealand Clinical Trials Registry; No.: ACTRN12613001299796; URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=364900.
RCT Entities:
RATIONALE: Dysregulation of the one carbon cycle is documented in depression. Thereby, S-adenosylmethionine (SAMe), a one-carbon cycle nutraceutical compound with a favourable side effect profile, has a theoretical rationale for efficacy. However, further controlled studies are required to confirm SAMe's efficacy. OBJECTIVES: To test the efficacy of SAMe versus placebo in unmedicated DSM-5 diagnosed (major depressive disorder) (MDD) patients with mild-to-moderate levels of depressive symptoms. METHODS: We conducted an 8-week, double-blind, randomised controlled trial testing 800 mg/day of SAMe monotherapy versus placebo in 49 patients with MDD (Montgomery-Åsberg Depression Rating Scale [MADRS] score 14-25) who were not currently taking antidepressants. One-carbon cycle biomarkers, brain-derived neurotropic factor (BDNF), and relevant single nucleotide polymorphisms (SNPs) were analysed as potential treatment moderators. RESULTS: A clinically relevant differential reduction from baseline to week 8 of 3.76 points occurred on the primary outcome (MADRS) in favour of SAMe. This however was not significant (p = 0.13) on an adjusted linear mixed model, notwithstanding a medium to large effect size of 0.72. A high placebo response rate of 53% occurred (> 50% reduction on MADRS). Exploratory analyses showed that SAMe was however effective in reducing depression amongst participants with milder depression severity (MADRS ≤ 22, p = 0.045). Response was not moderated by BDNF, SNPs, or one-carbon cycle biomarkers, although increased folate concentrations were correlated with improved symptoms in the SAMe group (r = - 0.57, p = 0.026). The treatment was safe and well tolerated. CONCLUSIONS: Although a differential reduction in depression symptoms between groups was observed in favour of SAMe, the results of this pilot study were not statistically significant. TRIAL REGISTRATION: ANZCTR-Australian New Zealand Clinical Trials Registry; No.: ACTRN12613001299796; URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=364900.
Authors: Jerome Sarris; Alexander Panossian; Isaac Schweitzer; Con Stough; Andrew Scholey Journal: Eur Neuropsychopharmacol Date: 2011-05-23 Impact factor: 4.600
Authors: Jerome Sarris; Jenifer Murphy; David Mischoulon; George I Papakostas; Maurizio Fava; Michael Berk; Chee H Ng Journal: Am J Psychiatry Date: 2016-04-26 Impact factor: 18.112
Authors: Anna Giménez-Palomo; Seetal Dodd; Gerard Anmella; Andre F Carvalho; Giselli Scaini; Joao Quevedo; Isabella Pacchiarotti; Eduard Vieta; Michael Berk Journal: Front Psychiatry Date: 2021-07-06 Impact factor: 4.157