Anesthesia-Informed Approaches to Insomnia: Shared Neural Circuits, Biomimetic Sleep, and Emerging Interventional Strategies.

Abstract

Background: Insomnia affects approximately 10-30% of adults, burdening quality of life, cognition, and health. Although cognitive behavioral therapy for insomnia (CBT-I) and approved pharmacotherapies remain standard care, limited accessibility, durability, and efficacy in refractory populations have motivated interest in mechanism-based alternatives, including approaches derived from anesthetic pharmacology.

Objective: This narrative review examines the convergent neural circuits underlying anesthesia-induced and physiological sleep, critically appraises evidence for anesthetic agents-dexmedetomidine, ketamine/esketamine, and propofol-delivered through non-traditional modalities, and evaluates perioperative sleep optimization, with explicit attention to evidence level and limitations.

Methods: We searched PubMed/MEDLINE, Embase, Web of Science, and the Cochrane Library for English-language publications through June 2026. Evidence from randomized controlled trials (RCTs), systematic reviews, observational studies, case reports, and mechanistic studies was synthesized narratively and graded using the Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence.

Results: Dexmedetomidine induces "biomimetic sleep" via alpha-2 adrenergic agonism, resembling natural non-rapid eye movement stage 2 sleep more closely than propofol. However, most supporting evidence is mechanistic, perioperative, or from small pilot studies rather than insomnia-specific RCTs. Patient-controlled sleep systems, intranasal delivery, and bionic sleep therapy are promising but preliminary, with incomplete long-term safety data, particularly regarding cardiovascular effects and withdrawal. Ketamine and esketamine may enhance slow-wave sleep, but most data derive from comorbid depression, confounding attribution. Stellate ganglion block, acupuncture, and closed-loop stimulation remain investigational and susceptible to placebo effects. Perioperative strategies improve postoperative sleep in RCTs, but extrapolation to chronic insomnia is limited by fundamental etiological differences.

Conclusion: Anesthesia-informed approaches provide mechanistic insights and investigational directions rather than established alternatives to CBT-I or approved hypnotics. Priorities include adequately powered insomnia-specific RCTs, comparison with standard treatments, long-term safety evaluation, and phenotype-guided selection.