Abstract
PURPOSE: Although Dexmedetomidine (DEX) can induce sleep that resembles natural sleep, it has demonstrated limited efficacy in patients with comorbid insomnia and depression. On the other hand, Esketamine (ESK) has shown a potent antidepressant effect. Herein, we aimed to establish whether esketamine could enhance the therapeutic efficacy of DEX in treating patients with comorbid insomnia and depression. METHODS: We recruited 84 patients with comorbid insomnia and depression who were randomized into two groups for a 1-month follow-up study: the DE group (receiving dexmedetomidine and esketamine) and the DS group (receiving dexmedetomidine and saline). Outcome measures included polysomnographic monitoring (PSG), Montgomery-Åsberg Depression Rating Scale (MADRS), Pittsburgh Sleep Quality Index (PSQI), Sleep Numeric Rating Scale (SNRS), and serum brain-derived neurotrophic factor (BDNF) concentrations. The primary outcome was a comparison of PSG parameters recorded at baseline (D(0)) and on treatment day 3 (D(3)). RESULTS: After 3 days of treatment, patients in DE group had a significant increase in total sleep duration, duration and proportion of N3 sleep (P < 0.05), a significant decrease in proportion of N2 sleep and proportion of REM sleep (P < 0.05), and a significant decrease in depression score and sleep numeric rating scale score (P < 0.05), as compared with DS group. Improvements in sleep were associated with improvements in MADRS score and increases in BDNF. Oral dryness was the most frequent adverse event (AE). CONCLUSION: When combined with ESK, DEX improved patients' depression scores, further extended total sleep time, increased the N3 sleep proportion, and enhanced deep sleep continuity, with few AEs.