The (cost-)effectiveness of exercise therapy adjunct to guideline-concordant care for depression: A pragmatic randomised controlled trial

Background: Many patients with major depressive disorder (MDD) do not respond sufficiently to first-line treatments. Due to its biological and psychological mechanisms of change, exercise therapy may enhance the effectiveness of other treatments in depression. In a pragmatic randomised superiority trial, we evaluated the clinical and cost-effectiveness of exercise therapy adjunct to guideline-concordant care as usual (CAU) for MDD in specialised mental health care.Methods: Outpatients with MDD (N = 112; Mage = 37 years; 51% female) were randomised to CAU, consisting primarily of psychotherapy (96.9%) and pharmacotherapy (59%), or CAU augmented with 12 weeks of exercise therapy (CAU+EX). Exercise therapy entailed one 45-minute supervised and two home-based moderate-intensity (i.e., 64–76% of HRmax) aerobic exercise sessions per week. Depressive symptoms were assessed every three weeks during the 12-week intervention and quarterly during the 12-month follow-up using the Inventory of Depressive Symptomatology-Self Report (IDS-SR). Remission was evaluated during follow-up by trained assessors using the Structured Clinical Interview for DSM-5 (SCID-5-S). The economic evaluation was conducted from a societal perspective.Results: Patients in the CAU+EX condition were significantly more likely than CAU to meet the exercise prescription, but still only 22% of patients adhered to the prescription. Depressive symptoms decreased from severe to moderate depression in both conditions, with no significant difference between the conditions on symptom reduction or remission rate. Evidence for cost-effectiveness was found in the per-protocol (≥ six supervised exercise sessions) but not in the intention-to-treat sample.Conclusions: Adjunct exercise therapy does not provide additional clinical benefits or cost-effectiveness for all MDD patients in specialized mental health care, who typically receive pharmacotherapy and psychotherapy. Low adherence to the exercise prescription limits its potential. Cost-effectiveness may be achievable with higher adherence, warranting emphasis on strategies to improve adherence, such as exploring how to personalize exercise protocols.