Lifestyle-Based Interventions for Major Depressive Disorder and Their Role Alongside Antidepressant Treatment: A Systematic Review

Major depressive disorder (MDD) remains disabling despite effective pharmacotherapy, and many patients experience an incomplete response or residual symptoms.This systematic review evaluated randomized trials of structured exercise or mind-body exercise, sleep/circadian and bright-light interventions, wholediet interventions, and multicomponent lifestyle programs delivered alongside antidepressant treatment in adults with current MDD.PubMed, Europe PMC, and ClinicalTrials.govwere searched from inception through September 15, 2026, with supplementary citation searching of eligible reports and relevant reviews.The electronic searches identified 1,310 records.After the removal of 333 duplicate bibliographic records and one non-usable record, 976 records underwent screening.Thirty-eight reports were assessed at full text.Following eligibility assessment and final verification, 26 eligible reports remained from the original search, and eight additional eligible reports were identified through supplementary citation searching.The final review included 34 reports representing 29 independent randomized studies.Risk of bias was assessed using the Cochrane Risk of Bias 2 (RoB 2) tool, certainty of evidence was evaluated using Grading of Recommendations Assessment, Development and Evaluation (GRADE), and results were synthesized without meta-analysis because substantial clinical and methodological heterogeneity made a pooled estimate inappropriate.Structured exercise showed the most consistent favorable signal, although effects were generally smaller or less certain in trials using active comparators.Sleep/circadian and bright-light interventions showed possible short-term benefits in selected studies, but findings varied by intervention, comparator, and assessment time, and sustained benefits were inconsistent.Evidence for multicomponent lifestyle programs was sparse, and no eligible randomized trial evaluated a whole-diet intervention alone as an adjunct to antidepressant treatment.Overall certainty of the evidence was low to very low because of risk of bias, inconsistency, and imprecision.Lifestyle-based interventions may provide additional benefit as adjuncts to antidepressant treatment, particularly structured exercise and selected sleep/circadian interventions; however, the magnitude and durability of benefit remain uncertain.Substitution of lifestyle interventions for antidepressant medication was not evaluated in this review.