Efficacy of exercise combined with standard treatment for depression compared to standard treatment alone: A systematic review and meta-analysis of randomized controlled trials

Background: Exercise is indicated as a monotherapy for depression, as well as an augmentation strategy alongside standard treatments. However, it is not yet clear how exercise and standard treatments interact with regards to patient outcomes. The primary aim of the current systematic review and meta-analysis was to compare the antidepressant effects of exercise combined with standard treatment to standard treatment alone. Method: A systematic search was conducted for trials comparing the efficacy of standard treatments alone or in combination with exercise for reducing symptoms of depression. Random effects meta-analysis was used to estimate pooled standardized mean difference for standard treatment alone versus standard treatment with exercise. Results: Twenty-two studies were included in the meta-analysis. There was a moderate pooled effect in favour of exercise combined with standard treatment compared to standard treatment alone (SMD = -0.62, p < 0.00001, I-2 = 70%), with greatest benefits accruing for more severe patients (SMD = -0.99, p < 0.00001; I-2 = 0%). Sensitivity analyses remained significant for trials with lower risk of bias (SMD = -0.41, p = 0.0009; I-2 = 52%) and patients with a major depressive disorder diagnosis (SMD = -0.70, p < 0.0001; I-2 = 72%). Limitations: There was considerable heterogeneity between trials. Uneven covariate distributions within subgroups limited our ability to explore the sources of heterogeneity. Conclusions: Exercise combined with standard treatments leads to significantly greater antidepressant effects over standard treatment alone. Patients and clinicians should consider using exercise alongside standard treatments to enhance therapeutic efficacy for depression.