Bot M, et al. - In this multicenter 2 × 2 factorial randomized clinical trial, researchers investigated whether a new major depressive disorder (MDD) episode in overweight adults with subsyndromal depressive symptoms could be effectively prevented by implementation of 2 nutritional strategies (multinutrient supplementation, food-related behavioral activation therapy) and their combination. In this patient population, no attenuation in the episodes of major depressive disorder was noted during 1 year with multinutrient supplementation vs placebo and food-related behavioral activation therapy vs no therapy. In view of these findings, these interventions were not supported as a preventive for major depressive disorder.

Methods

• Participants were recruited from 4 European countries and included 1025 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.
• Randomization was carried out from July 30, 2015 to October 12, 2016 and follow-up for 1 year was conducted till October 13, 2017.
• The components of the interventions were: 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.
• Researchers randomized 257 participants to placebo without therapy, 256 to placebo with therapy, 256 to supplements without therapy, and 256 to supplements with therapy.
• They performed the Mini International Neuropsychiatric Interview at 3, 6, and 12 months to assess cumulative 1-year onset of MDD.
• They assessed both individual and integrated (interaction) impacts of intervention on MDD onset via logistic regression using effect-coded variables (−1 indicating control, 1 indicating intervention) .

Results

• The trial was completed by 779 (76%) of 1025 participants (mean age, 46.5 years; 772 women [75%]; mean BMI, 31.4).
• MDD development was noted in 105 (10%) during 1year follow-up; this was reported in 25 (9.7%), 26 (10.2%), 32 (12.5%), and 22 (8.6%) patients in the respective groups: placebo without therapy, placebo with therapy, supplement without therapy, and supplement with therapy group.
• MDD onset remained uninfluenced by these treatment strategies.
• For supplements, for therapy, and for their combination, the estimated odds ratio (OR) were 1.06 (95% CI, 0.87-1.29), 0.93 (95% CI, 0.76-1.13), and 0.93 (95% CI, 0.76-1.14; P for interaction, .48), respectively.
• They reported death of one person in the supplementation with therapy group.
• Hospitalizations were reported in 24 patients in each of the placebo groups and 24 patients in the supplementation with therapy group, and 26 patients in the supplementation-only group.