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Esketamine prevents postoperative sleep disturbance in patients with preoperative sleep disorders: a role for oral microbiota.

Xin-Yu Li, Di Qiu, Ni Du, Kenji Hashimoto, Xing-Ming Wang, Jian-Jun Yang

Translational Psychiatry November 24, 2025 DOI: 10.1038/s41398-025-03705-9 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Randomized controlled trial Peer reviewed
Sample size 130
Population Patients undergoing surgery
Intervention Esketamine
Dose 0.3 mg/kg/h
Duration Postoperative days 1, 3, and 7
Topics Esketamine
Keywords Ketamine derivative Anesthetic Analgesic Postoperative recovery Surgical recovery Post-surgery care Enhanced recovery Surgical outcomes Sleep management Sleep disturbance Sleep quality Insomnia Sleep improvement Postoperative sleep Pain management Analgesia Pain relief Opioid reduction Postoperative pain Microbiome Oral microbiota Microbial communities Gut-brain axis
Citations 1
Key findings Intraoperative esketamine reduced the incidence of postoperative sleep disturbance on day 1 and was associated with altered oral microbiota profiles.

Abstract

Patients with preexisting sleep disorders face a significantly increased risk of postoperative sleep disturbance (PSD) due to heightened sensitivity to surgical stress, anesthesia, and hospital-related environmental factors. There is a critical unmet need for effective prophylactic medications to prevent PSD, as current treatment options are limited and often inadequate. This study investigated the prophylactic effect of intraoperative esketamine (0.3 mg/kg/h) on PSD in 130 patients randomized into control and esketamine groups. Preoperative sleep quality was assessed using the Pittsburgh Sleep Quality Index, while postoperative sleep was evaluated using the Numerical Rating Scale (NRS) and Athens Insomnia Scale (AIS) on postoperative days (PODs) 1, 3, and 7. PSD was defined as an NRS or AIS score ≥6. Saliva samples were collected for 16S rRNA sequencing to analyze the oral microbiota. On POD 1, the esketamine group showed a significantly lower incidence of PSD (43.1 vs. 64.6%; OR, 0.414; P = 0.014) and reduced hydromorphone consumption. Preoperative oral microbiota profiles differed between patients with and without PSD, with specific bacterial taxa associated with sleep disturbance. These findings suggest that esketamine may alleviate postoperative sleep disruption, potentially through modulation of the oral microbiota.

Comparable studies

Other randomized controlled trials on esketamine, most cited first.

Study Year Design Participants
Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study Adults with moderate to severe nonpsychotic depression and a history of nonresponse to... 2019 Phase 3, double-blind, active-controlled, multicenter randomized controlled trial n = 227
Efficacy of Esketamine Nasal Spray Plus Oral Antidepressant Treatment for Relapse Prevention in Patients With Treatment-Resistant Depression Adults with treatment-resistant depression who achieved stable remission or stable... 2019 Phase 3, multicenter, double-blind, randomized withdrawal study n = 297
Efficacy and Safety of Intranasal Esketamine Adjunctive to Oral Antidepressant Therapy in Treatment-Resistant Depression Adults with DSM-IV-TR diagnosis of major depressive disorder and history of inadequate... 2017 Phase 2, double-blind, doubly randomized, delayed-start, placebo-controlled study n = 67
Efficacy and Safety of Intranasal Esketamine for the Rapid Reduction of Symptoms of Depression and Suicidality in Patients at Imminent Risk for Suicide: Results of a Double-Blind, Randomized, Placebo-Controlled Study Depressed patients at imminent risk for suicide 2018 Randomized controlled trial n = 68
Efficacy and Safety of Fixed-Dose Esketamine Nasal Spray Combined With a New Oral Antidepressant in Treatment-Resistant Depression: Results of a Randomized, Double-Blind, Active-Controlled Study (TRANSFORM-1) Adults with moderate-to-severe depression and nonresponse to at least two... 2019 Randomized controlled trial n = 346

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