Associations of Combined Transcranial Magnetic Stimulation and Transcranial Direct Current Stimulation With Psychological and Functional Outcomes After Stroke: A Retrospective Cohort Study

Abstract

Background: To examine whether combined transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), delivered with standard rehabilitation, was associated with post-stroke depression and anxiety symptoms and secondary neurological and motor outcomes.

Methods: This retrospective cohort study included 180 patients classified according to treatment received in routine clinical practice: combined TMS + tDCS + standard rehabilitation (n = 60), standard rehabilitation alone (n = 60), TMS + standard rehabilitation (n = 30), or tDCS + standard rehabilitation (n = 30). Treatment selection reflected physician recommendations and patient preference. Beck Depression Inventory (BDI) and Generalized Anxiety Disorder 7-item scale (GAD-7) scores were primary outcomes; National Institutes of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS), and Fugl-Meyer Assessment (FMA) scores were secondary outcomes. Outcomes were assessed at baseline, 4 weeks, and 8 weeks. Generalized estimating equations adjusted for prespecified measured covariates assessed group, time, and group × time associations. Dunnett-adjusted comparisons used standard rehabilitation as the reference.

Results: No statistically significant differences were detected in the measured baseline characteristics (all p > 0.05). At 8 weeks, the combined group had lower median BDI scores [8.0 (6.0, 10.0) vs. 14.5 (11.5, 17.0)] and GAD-7 scores [6.0 (4.0, 8.0) vs. 9.0 (7.0, 11.0)] than the Standard Rehabilitation Group (both Dunnett-adjusted p < 0.001). Significant group × time associations were identified for BDI, GAD-7, NIHSS, mRS, and FMA outcomes (all p < 0.05). The combined group also had lower NIHSS and mRS scores and higher FMA scores than the standard rehabilitation group at 4 and 8 weeks. No severe adverse events were documented. Total recorded adverse-event rates were 8.3%, 5.0%, 3.3%, and 3.3% across the four groups, respectively, with no significant between-group difference (Fisher’s exact p = 0.584).

Conclusions: In this retrospective cohort, combined TMS and tDCS with standard rehabilitation was associated with lower depression and anxiety symptom scores and more favorable neurological and motor outcome trajectories than standard rehabilitation. Non-random treatment allocation and residual confounding preclude causal interpretation; prospective randomized studies are required.