Effects of Dual Orexin Receptor Antagonists on Seizure Quality in Modified Electroconvulsive Therapy

Objectives: Dual orexin receptor antagonists (DORAs) are widely used for insomnia treatment; however, their effects on seizure quality during modified electroconvulsive therapy (m-ECT) remain unclear. This study examined whether DORAs influence seizure parameters during m-ECT. Methods: A total of 239 m-ECT sessions in 54 patients (January 2022 to February 2025) were retrospectively analyzed. Patients were categorized into a DORA group (32 patients, 152 sessions) and a non-DORA group (22 patients, 87 sessions). Seizure quality was assessed using postictal suppression index, seizure duration, electroencephalogram (EEG) coherence, EEG amplitude, and peak heart rate (HR). Linear mixed-effects models evaluated each parameter and a composite Σz score (sum of standardized z-scores) with covariates including age, sex, chlorpromazine-equivalent dose, diagnosis (F2 vs. non-F2), ECT session number, thiopental dose, and percentage energy. Subgroup analyses included patients aged older than or equal to 60 years, within-DORA comparisons (suvorexant vs. lemborexant, dose-adjusted), and dose-response analyses limited to DORA-treated sessions. Results: No significant differences were observed in seizure quality parameters or the composite Σz score between groups. Among patients aged older than or equal to 60 years, peak HR tended to be lower with DORA exposure, whereas EEG-based seizure measures were maintained. No significant differences were found between suvorexant and lemborexant, and the DORA dose showed no linear relationship with Σz. Sensitivity analyses excluding landiolol, clozapine, or non-F2/F3 diagnoses yielded consistent results. Conclusions: DORA use during m-ECT did not impair seizure quality, supporting their safe concomitant use. Findings were consistent across subgroup, agent, and dose-response analyses. Larger prospective trials are warranted to confirm these results.