Bot Mariska, Brouwer Ingeborg A, Roca Miquel, Kohls Elisabeth, Penninx Brenda W J H, Watkins Ed, van Grootheest Gerard, Cabout Mieke, Hegerl Ulrich, Gili Margalida, Owens Matthew, Visser Marjolein
Amsterdam UMC, Vrije Universiteit, Psychiatry, Amsterdam Public Health research institute, GGZ inGeest Specialized Mental Health Care, Amsterdam, the Netherlands.
Department of Health Sciences, Faculty of Science and Amsterdam Public Health research institute, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
JAMA. 2019 Mar 5;321(9):858-868. doi: 10.1001/jama.2019.0556.
Effects of nutritional interventions on the prevention of major depressive disorder (MDD) in overweight adults are unknown.
To examine the effect of 2 nutritional strategies (multinutrient supplementation, food-related behavioral activation therapy) and their combination for prevention of a new MDD episode in overweight adults with subsyndromal depressive symptoms.
DESIGN, SETTING, AND PARTICIPANTS: This multicenter 2 × 2 factorial randomized clinical trial included overweight adults (body mass index, 25-40) with elevated depressive symptoms (Patient Health Questionnaire-9 [PHQ-9] scores ≥5) and no MDD episode in the past 6 months from 4 European countries. A total of 1025 adults were randomized (July 30, 2015-October 12, 2016) and followed up for 1 year (October 13, 2017).
Daily multinutrient supplements (1412-mg omega-3 fatty acids, 30-μg selenium, 400-μg folic acid, and 20-μg vitamin D3 plus 100-mg calcium) vs placebo and 21 individual or group therapy sessions vs none (blinded to researchers) for 1 year. Participants were allocated to placebo without therapy (n = 257), placebo with therapy (n = 256), supplements without therapy (n = 256), and supplements with therapy (n = 256).
Cumulative 1-year onset of MDD via the Mini International Neuropsychiatric Interview at 3, 6, and 12 months. Logistic regression using effect-coded variables (-1 indicating control, 1 indicating intervention) evaluated intervention effects both individually and in combination (interaction) on MDD onset.
Among 1025 participants (mean age, 46.5 years; 772 women [75%]; mean BMI, 31.4), 779 (76%) completed the trial. During the 12-month follow-up, 105 (10%) developed MDD: 25 (9.7%) patients in the placebo without therapy, 26 (10.2%) in the placebo with therapy, 32 (12.5%) in the supplement without therapy, and 22 (8.6%) in the supplement with therapy group. None of the treatment strategies affected MDD onset. The odds ratio (OR) for supplements was 1.06 (95% CI, 0.87-1.29); for therapy, 0.93 (95% CI, 0.76-1.13); and for their combination, 0.93 (95% CI, 0.76-1.14; P for interaction, .48). One person in the supplementation with therapy group, died. Twenty-four patients in each of the placebo groups and 24 patients in the supplementation with therapy group were hospitalized, and 26 patients in the supplementation-only group were hospitalized.
Among overweight or obese adults with subsyndromal depressive symptoms, multinutrient supplementation compared with placebo and food-related behavioral activation therapy compared with no therapy did not reduce episodes of major depressive disorder during 1 year. These findings do not support the use of these interventions for prevention of major depressive disorder.
ClinicalTrials.gov Identifier: NCT02529423.
营养干预对超重成年人预防重度抑郁症（MDD）的影响尚不清楚。
研究两种营养策略（多种营养素补充、与食物相关的行为激活疗法）及其联合使用对有亚综合征抑郁症状的超重成年人预防新发MDD发作的效果。
设计、设置和参与者：这项多中心2×2析因随机临床试验纳入了来自4个欧洲国家的超重成年人（体重指数，25 - 40），这些人抑郁症状加重（患者健康问卷 - 9[PHQ - 9]评分≥5）且在过去6个月内无MDD发作。共有1025名成年人被随机分组（2015年7月30日 - 2016年10月12日），并随访1年（2017年10月13日）。
每日服用多种营养素补充剂（1412毫克ω - 3脂肪酸、30微克硒、400微克叶酸、20微克维生素D3加100毫克钙）与安慰剂对比，以及接受21次个体或团体治疗课程与不接受治疗（对研究人员设盲）对比，为期1年。参与者被分配到无治疗的安慰剂组（n = 257）、有治疗的安慰剂组（n = 256）、无治疗的补充剂组（n = 256）和有治疗的补充剂组（n = 256）。
通过在3个月、6个月和12个月时进行的迷你国际神经精神病学访谈评估1年内MDD的累积发病情况。使用效应编码变量（-1表示对照，1表示干预）的逻辑回归分别评估干预措施及其联合使用（交互作用）对MDD发病的影响。
在1025名参与者中（平均年龄46.5岁；772名女性[75%]；平均BMI 31.4），779人（76%）完成了试验。在12个月的随访期间，105人（10%）患上MDD：无治疗的安慰剂组中有25人（9.7%），有治疗的安慰剂组中有26人（10.2%），无治疗的补充剂组中有32人（12.5%），有治疗的补充剂组中有22人（8.6%）。没有一种治疗策略影响MDD的发病。补充剂的优势比（OR）为1.06（95%CI，0.87 - 1.29）；治疗的OR为0.93（95%CI，0.76 - 1.13）；两者联合使用的OR为0.93（95%CI，0.76 - 1.14；交互作用P值为0.48）。有治疗的补充剂组中有1人死亡。安慰剂组各有24名患者以及有治疗的补充剂组中有24名患者住院，仅补充剂组中有26名患者住院。
在有亚综合征抑郁症状的超重或肥胖成年人中，与安慰剂相比，多种营养素补充以及与不接受治疗相比，与食物相关的行为激活疗法在1年内并未减少重度抑郁症的发作次数。这些发现不支持使用这些干预措施来预防重度抑郁症。
ClinicalTrials.gov标识符：NCT02529423。
