Preoperative anxiety is common and has clinical consequences. Pharmacologic premedication remains widely used; however, its effectiveness varies, in part due to misalignment between drug timing and peak anxiety, as well as differences in patient risk profiles. This review aimed to synthesize the pharmacology, efficacy, and safety of commonly used oral preoperative anxiolytics; identify patient groups at heightened risk who may benefit from premedication; and propose a pragmatic, pharmacokinetically informed framework for individualized drug selection and timing. A literature search was conducted using MEDLINE (PubMed), Embase, and Cochrane CENTRAL, supplemented by hand-searching of references and relevant guidelines. Benzodiazepines may provide reliable anxiolysis but require selective use in patients at risk of cognitive or respiratory complications. Melatonin offers modest anxiolysis with a favorable safety profile, particularly in older or frail patients. Gabapentinoids show inconsistent anxiolytic effects and should not be used primarily for this indication. Zolpidem has limited evidence for direct anxiolysis; any apparent benefit is likely indirect and mediated through sleep improvement. Clonidine and intranasal dexmedetomidine may offer context-specific benefits, although evidence remains limited in adults for dexmedetomidine. Aligning drug administration with pharmacokinetic profiles, particularly time to peak effect, may improve clinical effectiveness. An individualized, safety-prioritized approach that integrates pharmacologic and nonpharmacologic strategies is likely to optimize preoperative anxiolysis in diverse patient populations.
Seo et al. (Tue,) studied this question.