Zolpidem reduces pain intensity postoperatively: a systematic review and meta-analysis of the effect of hypnotic medicines on post-operative pain intensity

BACKGROUND: This systematic review aimed to investigate whether the administration of hypnotic medicines, z-drugs, melatonin or benzodiazepines, reduced pain intensity postoperatively. METHODS: Medline, Embase, Cinahl, Psych info, Central and PubMed databases were searched, from inception to February 2020 to identify relevant trials. The search was extended, post hoc, to include meta-Register of Controlled Trials, the Web of Science and the conference booklets for the 14th, 15th, and 16th International Association for the Study of Pain conferences. Two independent reviewers screened titles and abstracts and cross-checked the extracted data. RESULTS: The search retrieved 5546 articles. After full-text screening, 15 trials were included, which had randomised 1252 participants. There is moderate-quality evidence that in the short-term [WMD − 1.06, CI − 1.48 to − 0.64, p ≤ .01] and low-quality evidence that in the medium-term [WMD − 0.90, CI − 1.43 to − 0.37, p ≤ .01] postoperative period oral zolpidem 5/10 mg with other analgesic medicines reduced pain intensity compared to the same analgesic medicines alone. There is low-quality evidence that melatonin was not effective on postoperative pain intensity compared to placebo. The results of benzodiazepines on pain intensity were mixed. The authors reported no significant adverse events. CONCLUSIONS: There is promising evidence that the hypnotic medicine zolpidem, adjuvant to other analgesics, is effective at achieving a minimally clinically important difference in pain intensity postoperatively. There is no consistent effect of melatonin or benzodiazepines on postoperative pain intensity. Readers should interpret these results with some caution due to the lack of data on safety, the small number of trials included in the pooled effects and their sample sizes. SYSTEMATIC REVIEW REGISTRATION: The protocol for this systematic review was registered with PROSPERO ID=CRD42015025327.