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Abstract Objective To evaluate the feasibility and preliminary clinical signals of a risk‐stratified care pathway integrating multimodal markers to support the management of epilepsy with co‐occurring depressive or anxiety symptoms. Methods In this single‐center, assessor‐blinded, pilot randomized study (January 2023–January 2025), adults with epilepsy and clinically relevant depressive or anxiety symptoms (PHQ‐9 ≥ 10 or GAD‐7 ≥ 8) were allocated 1:1 to either a prespecified risk‐stratified stepped‐care pathway or guideline‐based usual care. The pathway used a multimodal risk score integrating electrophysiological, neuroimaging, pharmacogenomic, and clinical features to inform tiered monitoring and supportive interventions. Outcomes were assessed at 3 and 6 months. Results Implementation of the risk‐stratified pathway was feasible within routine clinical workflows. Compared with usual care, participants in the intervention group showed greater improvement in depressive symptoms and quality of life at 6 months, alongside favorable trends in seizure outcomes and treatment tolerability. Multimodal biomarkers demonstrated directionally consistent changes over follow‐up. All efficacy and biomarker findings are considered exploratory given the pilot design. Conclusion This pilot study demonstrates the feasibility of embedding a multimodal, risk‐stratified pathway into epilepsy care and provides hypothesis‐generating signals supporting further evaluation in adequately powered multicenter trials. The findings do not establish causal efficacy or warrant immediate changes to clinical practice.
Wang et al. (Sat,) studied this question.