Meta-analysis and meta-regression of omega-3 polyunsaturated fatty acid supplementation for major depressive disorder.
Meta-analysis and meta-regression of omega-3 polyunsaturated fatty acid supplementation for major depressive disorder.
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DOI：
10.1038/tp.2016.29
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发表时间：
2016-03-15
影响因子：
6.8
通讯作者：
Schene AH
中科院分区：
文献类型：
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作者：
Mocking RJ;Harmsen I;Assies J;Koeter MW;Ruhé HG;Schene AH
补充omega-3多不饱和脂肪酸(PUFA)已被提议作为严重抑郁障碍(MDD)的辅助治疗。在目前的荟萃分析中，我们合并了随机安慰剂对照试验，评估补充omega-3多不饱和脂肪酸对MDD抑郁症状的影响。此外，我们还进行了Meta回归，以检验补充效果是否依赖于二十碳五烯酸(EPA)或二十二碳六烯酸(EPA)的剂量、它们的比例、研究持续时间、参与者的年龄、抗抑郁药使用者的百分比、MDD症状严重程度基线、发表年份和研究质量。为了限制异质性，我们只纳入了通过标准化临床访谈评估的成年MDD患者的研究，排除了专门研究围产期/围绝经期或合并MDD的研究。我们在PubMed/EMBASE上检索到1955篇文章，其中包括13项研究，1233名参与者。在考虑了潜在的发表偏倚后，Meta分析显示omega-3 PUFAs对MDD患者的抑郁症状总体上是有益的(标准化均数差=0.398(0.114-0.682)，P=0.006，随机效应模型)。作为显著异质性的解释(I2=73.36P<；0.001)，Meta回归分析显示，较高的环丙沙星剂量(β=0.00037(0.00009-0.00065)，P=0.009)、较高的抗抑郁药使用率(β=0.0058(0.00017-0.01144)，P=0.044)和较早的发表年限(β=−0.0735(−0.143~0.0735)，P=0.04)与补充多不饱和脂肪酸的结果显著相关。另外还进行了敏感性分析。总而言之，目前的荟萃分析表明，补充omega-3多不饱和脂肪酸对MDD患者有有益的整体效果，特别是对于更高剂量的EPA和服用抗抑郁药物的参与者。未来的精确医学试验应该确定EPA和抗抑郁药之间可能的相互作用是否可以为改善抗抑郁药的反应及其预测提供靶点。此外，应仔细监测大剂量添加EPA补充剂可能产生的长期生化副作用。
Omega-3 polyunsaturated fatty acid (PUFA) supplementation has been proposed as (adjuvant) treatment for major depressive disorder (MDD). In the present meta-analysis, we pooled randomized placebo-controlled trials assessing the effects of omega-3 PUFA supplementation on depressive symptoms in MDD. Moreover, we performed meta-regression to test whether supplementation effects depended on eicosapentaenoic acid (EPA) or docosahexaenoic acid dose, their ratio, study duration, participants' age, percentage antidepressant users, baseline MDD symptom severity, publication year and study quality. To limit heterogeneity, we only included studies in adult patients with MDD assessed using standardized clinical interviews, and excluded studies that specifically studied perinatal/perimenopausal or comorbid MDD. Our PubMED/EMBASE search resulted in 1955 articles, from which we included 13 studies providing 1233 participants. After taking potential publication bias into account, meta-analysis showed an overall beneficial effect of omega-3 PUFAs on depressive symptoms in MDD (standardized mean difference=0.398 (0.114–0.682), P=0.006, random-effects model). As an explanation for significant heterogeneity (I2=73.36, P<0.001), meta-regression showed that higher EPA dose (β=0.00037 (0.00009–0.00065), P=0.009), higher percentage antidepressant users (β=0.0058 (0.00017–0.01144), P=0.044) and earlier publication year (β=−0.0735 (−0.143 to 0.004), P=0.04) were significantly associated with better outcome for PUFA supplementation. Additional sensitivity analyses were performed. In conclusion, present meta-analysis suggested a beneficial overall effect of omega-3 PUFA supplementation in MDD patients, especially for higher doses of EPA and in participants taking antidepressants. Future precision medicine trials should establish whether possible interactions between EPA and antidepressants could provide targets to improve antidepressant response and its prediction. Furthermore, potential long-term biochemical side effects of high-dosed add-on EPA supplementation should be carefully monitored.