Effective Doses and Predictors of Dexmedetomidine for Inducing Specific Sleep Stages (N2/N3) in Chronic Insomnia: A Retrospective Cohort Study

Background: Dexmedetomidine (DEX) has emerged as a potential agent for sleep modulation; however, the effective doses required to induce multimodal electroencephalography (EEG)–defined sleep stages in patients with chronic insomnia remain unclear. Objective: This study aimed to quantify the cumulative DEX doses required to induce non–rapid eye movement (NREM) stage N2 and N3 sleep and to identify clinical predictors of dose variability. Methods: In this single-center retrospective cohort study, we analyzed 252 adults with chronic insomnia who underwent standardized intravenous DEX titration under continuous multimodal EEG monitoring. The primary outcomes were the cumulative DEX doses (μg) required to induce sustained N2 or N3 sleep. Univariable and multivariable linear regression models were used to identify independent predictors, including body mass index (BMI), depressive symptom severity assessed by the Montgomery–Åsberg Depression Rating Scale (MADRS), and other clinically relevant covariates. Restricted cubic spline analyses were performed to examine potential nonlinear associations between BMI and DEX dose. Prespecified subgroup analyses stratified by age (< 60 vs. ≥ 60 years) were conducted to assess effect modification. Results: The median effective dose was 40 μg (interquartile range [IQR], 33– 48) for N2 sleep induction and 55 μg (IQR, 48– 64) for N3 sleep induction. BMI was independently associated with higher DEX dose requirements for both N2 (adjusted β = 0.71; 95% CI, 0.25– 1.17; P = 0.003) and N3 sleep (adjusted β = 0.48; 95% CI, 0.07– 0.89; P = 0.022). Higher MADRS scores were independently associated with increased DEX dose for N2 sleep induction (adjusted β = 0.17; 95% CI, 0.01– 0.34; P = 0.041) but not for N3 sleep. Restricted cubic spline analyses demonstrated significant overall associations between BMI and DEX dose for both sleep stages, while tests for nonlinearity were not statistically significant. Age was not significantly associated with DEX dose requirements, and no significant interaction by age group was observed. Conclusion: In patients with chronic insomnia, higher cumulative doses of DEX are required to induce deeper NREM sleep stages. BMI is a key determinant of DEX dose requirements for both N2 and N3 sleep, whereas depressive symptom severity appears to selectively influence N2 sleep induction. These findings support the use of individualized, multimodal EEG-guided DEX titration strategies and provide preliminary data to inform future prospective dose-finding studies. Keywords: dexmedetomidine, chronic insomnia, dose-finding, body mass index, depression, personalized medicine