Although there is no significant heterogeneity, this low inconsistency may be caused by several reasons. First, different routes of melatonin administration are involved in our included RCTs. Second, the doses of melatonin intervention range from 5 to 10 mg. Most human clinical studies have focused on the doses of 3 to 15 mg melatonin but its doses are up to 300 mg/kg in experimental animal studies.14 Optimal dosing and a strict dose-response relationship remain to be investigated further. Third, the different timing of administration is critical for the analgesic effect. In addition, studies have reported that the administration of melatonin is a safe drug, without serious adverse effects.35 Our meta-analysis finds no increase in adverse events including headache, depression, and dizziness after melatonin intervention for laparoscopic cholecystectomy.
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