Integrated rehabilitation for post-stroke anxiety: a prospective, multicenter, randomized controlled trial

Introduction Post-stroke anxiety (PSA) affects approximately one-quarter of stroke survivors and impedes functional recovery, yet pharmacological options remain limited by inconsistent efficacy and absent standardized guidelines. This study evaluated an integrated rehabilitation program combining repetitive transcranial magnetic stimulation (rTMS), acupuncture, and Chinese herbal medicine for PSA. Methods In this multicenter randomized controlled trial, 188 participants with mild-to-moderate PSA were randomized 1:1 to standard care (pharmacotherapy, general care, and exercise therapy) or integrated rehabilitation (standard care plus rTMS, acupuncture, and Chinese herbal medicine) for 4 weeks, with an 8-week follow-up. The primary outcome was the Hamilton Anxiety Rating Scale (HAM-A). Secondary outcomes included the Self-Rating Anxiety Scale (SAS), Activities of Daily Living (ADL), Instrumental Activities of Daily Living (IADL), Montreal Cognitive Assessment (MoCA), Fugl–Meyer Assessment (FMA), and Pittsburgh Sleep Quality Index (PSQI). Analyses followed an intention-to-treat framework. Results The integrated rehabilitation group showed significantly greater reductions in HAM-A scores at Week 4 than controls (between-group difference, 2.49 points; 95% CI, 1.50 to 3.48; p <0.01), and this treatment benefit was maintained at week 12 (p<0.01). In supportive analyses of the secondary outcomes, Holm-adjusted group × time interactions remained significant for PSQI, MoCA, upper-extremity motor function, ADL, and SAS scores (all adjusted p<0.05), but not for lower-extremity motor function or IADL. Discussion The integrated rehabilitation program improved the primary anxiety outcome and provided supportive evidence of broader clinical benefits in sleep quality, cognition, and upper-extremity motor function, together with distinct patterns of functional change in ADL and IADL. Overall, these findings support further consideration of this integrated approach as an adjunct to pharmacotherapy for PSA. Biological mechanisms and contributions of individual intervention components remain undetermined. Further mechanistic investigations incorporating biological measures would help clarify the underlying mechanisms. Clinical trial registration https://clinicaltrials.gov/ , identifier NCT05147077.