Neurology · Medical Literature
Nonlinear dose-response effects of exercise interventions on post-stroke depression: a systematic review and meta-analysis.
Abstract
To systematically evaluate the effects of exercise interventions on post-stroke depression (PSD) and to clarify the dose-response relationship between physical activity dosage and depressive symptoms in individuals with PSD. A structured and comprehensive search was conducted in PubMed, Web of Science, Embase, Scopus, and the Cochrane Library. Restricted cubic spline models were applied to examine the dose-response association between physical activity dosage and depressive symptoms in PSD. A total of 27 publications comprising 31 randomized controlled trials were included, involving 2,247 participants. The meta-analysis indicated that exercise intervention was associated with a modest improvement in depressive symptoms among patients with PSD [SMD = -0.15, 95% CI (-0.23, -0.07), p < 0.01], with moderate heterogeneity (I 2 = 41.9%). Dose-response analysis revealed a non-linear association between exercise dosage and symptom improvement, with the greatest apparent benefit observed at approximately 801 MET-min/week. Subgroup analyses suggested that more favorable improvements were more commonly observed in interventions characterized by resistance training [SMD = -0.55, 95% CI (-0.85, -0.25)], a frequency of 1-2 sessions per week [SMD = -0.41, 95% CI (-0.67, -0.15)], a session duration of ≤30 min [SMD = -0.44, 95% CI (-0.70, -0.19)], and an intervention duration of 9-12 weeks [SMD = -0.16, 95% CI (-0.27, -0.05)]. Moderate-dose exercise intervention, approximately 801 MET-min/week, was associated with a modest improvement in post-stroke depressive symptoms. These findings provide a reference for optimizing exercise dosage and informing individualized prescription strategies for patients with PSD. https://www.crd.york.ac.uk/PROSPERO/view/CRD420251167322, identifier (CRD420251167322).
Clinical relevance
Post-stroke depression (PSD) affects a substantial proportion of stroke survivors and is associated with poorer functional recovery, reduced quality of life, and increased mortality, yet optimal non-pharmacological management strategies remain incompletely defined. This systematic review and meta-analysis of 31 RCTs (n = 2,247) addresses a critical evidence gap by quantifying the dose-response relationship between structured exercise and depressive symptom reduction in PSD. Clarifying the optimal exercise prescription is clinically urgent given patient heterogeneity, polypharmacy concerns, and the need for individualized rehabilitation protocols in stroke care.
Key findings
1. Overall effect: Exercise intervention was associated with a statistically significant but modest reduction in depressive symptoms compared to control conditions (SMD = -0.15, 95% CI [-0.23, -0.07], p < 0.01), with moderate heterogeneity across trials (I² = 41.9%). 2. Dose-response nonlinearity: Restricted cubic spline modeling revealed a non-linear (rather than linear) dose-response relationship between exercise dosage and symptom improvement, with peak apparent benefit observed at approximately 801 MET-min/week. 3. Exercise modality: Resistance training was associated with the largest effect size among modalities examined (SMD = -0.55, 95% CI [-0.85, -0.25]), suggesting superior antidepressant efficacy over other exercise types in PSD. 4. Session frequency: A frequency of 1–2 sessions per week yielded more favorable outcomes than higher-frequency protocols (SMD = -0.41, 95% CI [-0.67, -0.15]). 5. Session duration: Shorter session durations of ≤30 minutes were associated with greater symptom improvement compared to longer sessions (SMD = -0.44, 95% CI [-0.70, -0.19]). 6. Intervention duration: An intervention length of 9–12 weeks was associated with significant depressive symptom reduction (SMD = -0.16, 95% CI [-0.27, -0.05]), providing a pragmatic timeframe benchmark for clinical program design.
Practice implications
Stroke rehabilitation programs should incorporate structured exercise—preferably resistance training—targeting approximately 801 MET-min/week, delivered in sessions of ≤30 minutes at a frequency of 1–2 times per week over a 9–12 week course, as this profile is associated with the most favorable antidepressant outcomes in PSD patients. Clinicians should avoid a one-size-fits-all high-frequency or high-volume approach, as the identified non-linear dose-response curve suggests that exceeding the optimal dose threshold may attenuate benefit, and individualized prescription accounting for post-stroke functional capacity is essential. Routine screening for PSD combined with early integration of tailored exercise prescriptions into multidisciplinary stroke rehabilitation plans is warranted, with reassessment of depressive symptoms at 9–12 weeks to evaluate treatment response.