Dose-response effects of aerobic exercise on reducing depression in patients with chronic illness and comorbid depression: a systematic review and meta-analysis

Importance Aerobic exercise is an evidence-based treatment for depression. However, current exercise recommendations do not account for the limited functional capacity of patients with chronic illness and comorbid depression. Consequently, these recommendations risk being inappropriate and having low therapeutic application in this population. Objective To examine the dose-response relationship between aerobic exercise volume and the severity of depressive symptoms, and to determine the exercise volume needed to alleviate depressive symptoms to the minimally important difference (MID) threshold in patients with chronic illness and comorbid depression. Data sources We searched four databases (PubMed, Embase, Web of Science and PsycINFO) for randomised controlled trials published between database inception and May 2025, without language restrictions. Study selection We included studies that compared the effects of aerobic exercise interventions with passive controls on depressive symptoms in adults with chronic illness and comorbid depression. Data extraction and synthesis Data extraction was performed independently by two reviewers using a standardised form. A random-effects meta-analysis was employed to calculate the pooled estimate (Hedges’ g) and the 95% CI. Meta-regression was conducted to determine the dose-response relationship between aerobic exercise volume and the severity of depressive symptoms. Main outcome and measure The prespecified primary outcome was depressive symptoms and was assessed using validated depression rating scales. Results 36 randomised controlled trials involving 2500 patients were included. Aerobic exercise compared with passive controls reduced the severity of depressive symptoms in patients with chronic illness and comorbid depression (Hedges’ g: −0.73, 95% CI −0.99 to –0.46, p<0.001, I2=81%). Additionally, aerobic exercise had a dose-response effect of −0.01 (95% CI −0.016 to –0.002, p=0.014) per 10 metabolic equivalent of task minutes per week (MET-min/week) on the severity of depressive symptoms. A weekly volume of 405 MET-min/week was found to alleviate depressive symptoms to an extent perceived as important (MID) by patients with chronic illness and comorbid depression. Conclusions and relevance This study presents a dose-response relationship between aerobic exercise volume and the severity of depressive symptoms, suggesting that minimal volumes of aerobic exercise can confer improvements. Importantly, it informs stakeholders that achieving the WHO recommendation of 450 MET-min/week is not mandatory to elicit improvements in depressive symptoms. These findings underscore that irrespective of the functional capacity of patients with chronic illness and comorbid depression, aerobic exercise remains a viable strategy to manage their depressive symptoms. PROSPERO registration number CRD42021282103. © Author(s) (or their employer(s)) 2026.