Effect of Multinutrient Supplementation and Food-2 Related Behavioral Activation Therapy on 3 Prevention of Major Depressive Disorder Among 4 Overweight or Obese Adults With Subsyndromal 5 Depressive Symptoms

Abstract

Importance: Effects of nutritional interventions on the prevention of major depressive disorder (MDD) in overweight adults are unknown. Objective: To examine the effect of two nutritional strategies (multi-nutrient supplementation, food-related behavioral activation (F-BA) therapy) and their combination for prevention of a new MDD episode in overweight adults with subsyndromal depressive symptoms. Design, setting, participants: This multicenter 2x2 factorial randomized clinical trial included overweight adults (BMI 25-40kg/m2) aged 18-75years with elevated depressive symptoms (Patient Health Questionnaire-9 (PHQ-9) scores≥5) not meeting criteria for MDD episodes in the past 6 months from 4 European countries. 1025 adults were randomized between July-30-2015 and October-12-2016, and followed for 1 year (until October-13-2017). Interventions: Daily multi-nutrient supplements (1412mg omega-3 fatty acids, 30μg selenium, 400μg folic acid, and 20μg D-3 vitamin plus 100mg calcium) versus placebo (blinded), and/or 21 individual and group F-BA sessions versus no F-BA (blinded to researchers), for one year. Participants were allocated to placebo without F-BA (n=257), placebo with F-BA (n=256), supplements without F-BA (n=256), and supplements with F-BA (n=256). Main Outcomes and Measures: Primary outcome was cumulative 1-year onset of MDD measured with the Mini International Neuropsychiatric Interview after 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. Results: Among 1025 participants (mean age 46.5y; 772 (75%) women; mean BMI 31.4kg/m2), 779 (76%) completed the trial. During 12 month follow-up, 105 (10%) developed MDD (placebo without F-BA: 25 (9.7%), placebo with F-BA: 26 (10.2%), supplements without F-BA: 32 (12.5%), supplements with F-BA: 22 (8.6%).. Neither supplements (odds ratio (OR)=1.06; 95%-confidence interval (CI)=0.87-1.29), F-BA (OR=0.93; 95%CI=0.76-1.13), nor their combination (OR=0.93; 95%CI=0.76-1.14, p for interaction=0.48) affected MDD onset. Number of deaths/hospitalizations were for placebo without F-BA (n=0,n=24), placebo with F-BA (n=0,n=24), supplements without F-BA (n=0,n=26) and supplements with F-BA (n=1,n=24), respectively. Conclusions and Relevance: Among overweight or obese adults with depressive symptoms, multi-nutrient 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. Trial registration: https://www.clinicaltrials.gov/ct2/show/NCT02529423. August-2015.