Preoperative Sleep Modulation with Melatonin and Zolpidem and Its Impact on Postoperative Pain and Recovery: A Scoping Review

Perioperative sleep disturbances and anxiety may worsen postoperative pain, increase opioid consumption, and delay recovery. Melatonin and zolpidem improve sleep, but their effects on postoperative pain remain incompletely characterized. PubMed, Embase, and Scopus were searched for studies published between 2000 and 2025 investigating preoperative melatonin or zolpidem in surgical patients. Two reviewers independently screened records using Rayyan, resolving discrepancies through consensus. Of 404 records identified, 119 duplicates were removed. Of 285 screened records, 269 were excluded, leaving 16 articles for inclusion. Melatonin demonstrated anxiolytic, analgesic, and chronobiotic effects. It reduced salivary cortisol, modulated stress responses, attenuated proinflammatory pathways, and supported circadian recovery, particularly in patients with preoperative anxiety. Its analgesic efficacy was comparable to clonidine in some trials, with a favorable safety profile. Zolpidem improved preoperative sleep quality and reduced postoperative pain and opioid consumption, potentially through improved sleep architecture. In colorectal surgery, zolpidem also reduced tumor necrosis factor-alpha (TNF-α). Melatonin demonstrated more consistent effects on cortisol, suggesting distinct physiological mechanisms. Melatonin and zolpidem offer complementary perioperative benefits. Melatonin may provide broader neuroendocrine and analgesic effects, whereas zolpidem may benefit patients with insomnia. Larger trials are needed to optimize dosing and patient selection.