Exercise as adjunctive therapy for depression: Evidence, mechanisms, and individualized prescription

Depression is frequently accompanied by residual symptoms, physical inactivity, and cardiometabolic comorbidity.Exercise offers a potentially useful treatment component that can address mood and physical function, but clinical efficacy, biological plausibility, and causal mediation should be distinguished.This narrative minireview integrates randomized trials, evidence syntheses, clinical guidance, and mechanistic research to evaluate exercise as an adjunctive intervention for adults with unipolar depression.Recent syntheses, including the 2026 Cochrane update, support reductions in depressive symptoms compared with inactive or control conditions, although methodological limitations and heterogeneous comparators reduce certainty.Walking or jogging, resistance training, yoga, and mixed aerobic programs have supportive evidence; available comparisons do not establish a universally superior modality or equivalence to established psychiatric treatments.Proposed mechanisms include neuroplasticity, reward and endocannabinoid signaling, stress-system regulation, inflammatory and metabolic adaptations, sleep-circadian effects, and behavioral activation.Much of the mechanistic evidence is preclinical or based on peripheral biomarkers, and clinical mediation remains incompletely established.Physical fitness and metabolic outcomes may improve independently of mood, whereas evidence for sustained remission, relapse prevention, and reduction of major physical-health events in depressed populations remains limited.Prescription should account for clinical risk, symptom burden, medical comorbidity, baseline fitness, preferences, access, and adherence.Gradual progression and coordinated follow-up are more defensible than a fixed universal dose.Biomarkerguided selection and chronotype-based timing remain research priorities rather than validated prescribing tools.Exercise should be integrated into shared decision-making and should never delay urgent psychiatric treatment.