From the ARCADIA Mental Health Research Group, Professorial Unit, Department of Psychiatry, The Melbourne Clinic, University of Melbourne, Melbourne, Australia; the Centre for Human Psychopharmacology, Swinburne University of Technology, Melbourne, Australia; the Depression Clinical and Research Program, Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston; the IMPACT Strategic Research Centre, School of Medicine, Deakin University, Barwon Health, Geelong, Australia; Orygen, the National Centre of Excellence in Youth Mental Health and the Centre of Youth Mental Health, Melbourne, Australia; and the Florey Institute for Neuroscience and Mental Health, Melbourne, Australia.
Am J Psychiatry. 2016 Jun 1;173(6):575-87. doi: 10.1176/appi.ajp.2016.15091228. Epub 2016 Apr 26.
There is burgeoning interest in augmentation strategies for improving inadequate response to antidepressants. The adjunctive use of standardized pharmaceutical-grade nutrients, known as nutraceuticals, has the potential to modulate several neurochemical pathways implicated in depression. While many studies have been conducted in this area, to date no specialized systematic review (or meta-analysis) has been conducted.
A systematic search of PubMed, CINAHL, Cochrane Library, and Web of Science was conducted up to December 2015 for clinical trials using adjunctive nutrients for depression. Where sufficient data were available, a random-effects model analyzed the standard mean difference between treatment and placebo in the change from baseline to endpoint, combining the effect size data. Funnel plot and heterogeneity analyses were also performed.
Primarily positive results were found for replicated studies testing S-adenosylmethionine (SAMe), methylfolate, omega-3 (primarily EPA or ethyl-EPA), and vitamin D, with positive isolated studies for creatine, folinic acid, and an amino acid combination. Mixed results were found for zinc, folic acid, vitamin C, and tryptophan, with nonsignificant results for inositol. No major adverse effects were noted in the studies (aside from minor digestive disturbance). A meta-analysis of adjunctive omega-3 versus placebo revealed a significant and moderate to strong effect in favor of omega-3. Conversely, a meta-analysis of folic acid revealed a nonsignificant difference from placebo. Marked study heterogeneity was found in a Higgins test for both omega-3 and folic acid studies; funnel plots also revealed asymmetry (reflecting potential study bias).
Current evidence supports adjunctive use of SAMe, methylfolate, omega-3, and vitamin D with antidepressants to reduce depressive symptoms.
人们对提高抗抑郁药治疗效果不佳的增强策略越来越感兴趣。辅助使用标准化的医药级营养素，即所谓的“营养保健品”，有可能调节几种与抑郁症相关的神经化学途径。尽管在这一领域已经进行了许多研究，但迄今为止尚未进行专门的系统评价（或荟萃分析）。
系统检索了 PubMed、CINAHL、Cochrane 图书馆和 Web of Science，以查找截至 2015 年 12 月使用辅助营养素治疗抑郁症的临床试验。在有足够数据的情况下，使用随机效应模型分析了从基线到终点治疗与安慰剂之间的标准均数差值，合并了效应大小数据。还进行了漏斗图和异质性分析。
对重复研究测试 S-腺苷甲硫氨酸（SAMe）、甲基叶酸、ω-3（主要是 EPA 或乙基-EPA）和维生素 D 的研究，主要发现了阳性结果，对肌酸、叶酸和氨基酸组合的阳性孤立研究也进行了测试。锌、叶酸、维生素 C 和色氨酸的结果则较为复杂，而肌醇的结果则不显著。研究中未发现重大不良反应（除了轻微的消化紊乱）。辅助性 ω-3 与安慰剂的荟萃分析显示，ω-3 具有显著且中等至强的效果。相反，叶酸与安慰剂的荟萃分析显示无显著差异。在对 ω-3 和叶酸研究的 Higgins 检验中发现了明显的研究异质性；漏斗图也显示了不对称性（反映了潜在的研究偏差）。
目前的证据支持在抗抑郁药治疗中辅助使用 SAMe、甲基叶酸、ω-3 和维生素 D 来减轻抑郁症状。
