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Clinical Trial
. 2025 Jul 12:21:1409-1423.
doi: 10.2147/NDT.S530265. eCollection 2025.

Esketamine Optimized the Efficacy of Dexmedetomidine in Treating Sleep Disorders with Comorbid Depression

Yitong Ding #  1 , Zhengye Wang #  1 , Jing Huang  1 , Yanzi Yi  1 , Zhouquan Wu  2
Affiliations
Clinical Trial

Esketamine Optimized the Efficacy of Dexmedetomidine in Treating Sleep Disorders with Comorbid Depression

Yitong Ding et al. Neuropsychiatr Dis Treat. .

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 (D0) and on treatment day 3 (D3).

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.

Keywords: depression; dexmedetomidine; esketamine; insomnia; polysomnography.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Schematic Representation of EEG Signal Power Distribution Monitoring via Multimodal EEG. (a): Schematic diagram of electrode connection; (b): EEG spectra during dexmedetomidine titration; 0–4Hz for delta wave, 4–8Hz for theta wave, 8–12Hz for alpha wave, 13–35Hz for beta wave; “L” means left hemisphere, “R” means right hemisphere.
Figure 2
Figure 2
Polysomnographic Sleep Monitoring and Stage-Specific Waveforms (Schematic). (a) Schematic diagram of polysomnography monitoring electrodes; (b) Polysomnography of N2 sleep; (c) Polysomnography of N3 sleep; (d) Polysomnography of REM sleep.
Figure 3
Figure 3
Participant Flowchart.
See this image and copyright information in PMC

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