Efficacy of aerobic exercise as a combination therapy for depression compared to standardized therapy: a systematic review and meta-analysis of randomized controlled trials

Utilizing aerobic exercise prevails as a popular choice for physical activity, serving as the predominant exercise intervention for addressing depression. It is also used as supplementary therapy to standardized treatments, including pharmacotherapy, psychotherapy, and treatment as usual (TAU). Despite this, the therapeutic mechanism of aerobic exercise as an adjunctive therapy, as well as its interaction with standardized treatments, has not been fully elucidated. The primary goal of the current study was to evaluate the effectiveness of aerobic exercise as an adjunct to these standardized treatments in enhancing the antidepressant effect, compared with standardized treatment alone. We systematically searched randomized controlled trials that compared the efficacy of combining aerobic exercise with standardized therapy against standardized therapy alone in treating depression. The final analysis incorporated 20 trials, with a total of 914 participants. Calculation of the pooled standardized mean difference between aerobic exercise combined therapy and standardized therapy was conducted using a random-effects model. Compared with standardized therapy alone, aerobic exercise combined therapy demonstrated a significant moderate effect (SMD = -0.72 [-0.96, -0.47], p < 0.00001, I² = 66%). In subgroup analyses, older patients showed a numerically larger effect, but the age subgroup difference was not statistically significant (p = 0.06). In analyses stratified by standardized treatment modality, aerobic exercise combined with pharmacotherapy showed the largest effect (SMD = -0.97 [-1.41, -0.54], p < 0.0001, I² = 78%), and the between-subgroup difference was significant (p = 0.02). In addition to antidepressant effects, aerobic exercise combined therapy was also associated with improvements in other health-related outcomes. Subgroup findings further suggested that both low- and moderate-intensity aerobic exercise were associated with favorable treatment outcomes, with low-intensity exercise showing potential in patients with lower baseline physical fitness or more severe depressive symptoms. Moreover, a higher total exercise dose was generally associated with greater therapeutic benefit. Aerobic exercise may be a useful adjunct to standardized treatment for depression and may help improve overall treatment outcomes. However, these findings should be interpreted cautiously given the substantial heterogeneity across studies, the conceptual breadth of “standardized therapy,” and the limited evidence available for several secondary outcomes. Future studies should further clarify the optimal exercise prescription, underlying mechanisms, and long-term effectiveness across different patient subgroups.