Effect of Multinutrient Supplementation and Food-Related Behavioral Activation Therapy on Prevention of Major Depressive Disorder Among Overweight or Obese Adults With Subsyndromal Depressive Symptoms: The MooDFOOD Randomized Clinical Trial

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 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).

Interventions: 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).

Main outcome and measures: 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.

Results: 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.

Conclusions and relevance: 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.

Trial registration: ClinicalTrials.gov Identifier: NCT02529423.

Figure 1.. Flow of Participants Through the MooDFOOD Depression Prevention Trial

^aBipolar disorder, schizophrenia, psychosis, eating disorder, anxiety disorder, alcohol, drug, or substance addiction. ^bCumulative loss to follow-up is defined as having no MDD measurement at month 12. ^cThe primary analysis included all participants according to their randomization group, including all participants randomized regardless of the intervention actually received or of study withdrawal. Missing data were multiple imputed. BMI indicates body mass index; MDD, major depressive disorder; PHQ, Patient Health Questionnaire.

Figure 2.. Course of Depressive Symptoms, Anxiety Symptoms, and Health Utility per Intervention Group

The boxplot inner horizontal lines represent the median, the boxes represent the interquartile range (25% and 75%), the vertical whiskers represent the 1.5 interquartile range beyond the 25th and 75th percentiles, and the dots represent all other values. The diamonds represent the means. The dark blue bars indicate the intervention; the light blue bars, control. The No. of participants represents the number of persons who completed the secondary outcomes at the different time points. Data shown are the available data.