NICM Health Research Institute, Westmead, Western Sydney University, Locked Bag 1797, Penrith, NSW, 2751, Australia.
Professorial Unit, The Melbourne Clinic, Department of Psychiatry, Melbourne University, Melbourne, Australia.
Psychopharmacology (Berl). 2020 Jan;237(1):209-218. doi: 10.1007/s00213-019-05358-1. Epub 2019 Nov 11.
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.
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.
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.
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.
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.
ANZCTR-Australian New Zealand Clinical Trials Registry; No.: ACTRN12613001299796; URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=364900.
一碳循环的失调在抑郁症中已有记载。因此，S-腺苷甲硫氨酸（SAMe）是一种具有良好副作用谱的一碳循环营养化合物，具有理论上的疗效。然而，还需要进一步的对照研究来证实 SAMe 的疗效。
在未经药物治疗的 DSM-5 诊断为（重性抑郁障碍）（MDD）的患者中，测试 SAMe 与安慰剂在轻度至中度抑郁症状患者中的疗效。
我们进行了一项为期 8 周、双盲、随机对照试验，在 49 名未服用抗抑郁药的 MDD 患者（蒙哥马利-阿斯伯格抑郁评定量表[MADRS]评分 14-25）中，测试了 800mg/天的 SAMe 单药治疗与安慰剂的疗效。一碳循环生物标志物、脑源性神经营养因子（BDNF）和相关的单核苷酸多态性（SNP）被分析为潜在的治疗调节剂。
主要结局（MADRS）从基线到第 8 周的临床相关差异下降了 3.76 分，有利于 SAMe。然而，在调整后的线性混合模型中，这并不显著（p=0.13），尽管效应大小为 0.72。高安慰剂反应率为 53%（MADRS 下降>50%）。探索性分析表明，SAMe 对抑郁严重程度较轻的患者（MADRS ≤22，p=0.045）确实有效。BDNF、SNP 或一碳循环生物标志物并没有调节反应，尽管 SAMe 组的叶酸浓度升高与症状改善相关（r=-0.57，p=0.026）。治疗安全且耐受良好。
尽管观察到组间抑郁症状的差异有利于 SAMe，但这项初步研究的结果并不具有统计学意义。
澳大利亚新西兰临床试验注册中心；编号：ACTRN12613001299796；网址：https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=364900。
