Recommended timing of medications that impact sleep and wakefulness: A review of the American Prescribers' Digital Reference

Sleep Med Rev. 2023 Feb;67:101714. doi: 10.1016/j.smrv.2022.101714. Epub 2022 Nov 8.


An appreciable number of medicines have a recommended unique single time-of-day or asymmetrical or unequal-interval multiple-daily administration schedule. Many prescription and over-the-counter (OTC) products, according to administration time, can exert positive or negative impact on nighttime sleep and daytime wakefulness. Intuitively, medicines used to manage nighttime sleep and daytime wake disorders should be taken, respectively, at night before bedtime and morning after arising. However, some utilized for other medical conditions, if improperly timed, may compromise nocturnal sleep and diurnal attentiveness. We conducted a comprehensive review of the American Prescribers' Digital Reference, internet version of the Physician's Desk Reference, for the recommended scheduling of medications and OTC remedies that can impact sleep and wakefulness. The search revealed several hundred therapies of various classes -- α2-receptor agonists, antidepressants, barbiturates, central nervous system stimulants, benzodiazepines, dopamine agonists, dopamine norepinephrine reuptake inhibitors, selective norepinephrine reuptake inhibitors, eugeroics, γ-aminobutyric acid modulators, H1 and H3-receptor antagonists, melatonin analogues, OTC melatonin-containing products, non-benzodiazepine benzodiazepine-receptor agonists, dual orexin-receptor antagonists, and serotonin modulators -- that have a recommended unique dosing schedule. The tables and text of this article are intended to guide the proper scheduling of these medicines to optimize desired and/or minimize undesired effects.

Keywords: Administration time; American Prescribers' Digital Reference; Medications; Sleep promotion and disturbance; Wakefulness promotion and disturbance.

Publication types

  • Review

MeSH terms

  • Antidepressive Agents
  • Humans
  • Melatonin* / therapeutic use
  • Norepinephrine / pharmacology
  • Sleep / physiology
  • Wakefulness* / physiology


  • Melatonin
  • Antidepressive Agents
  • Norepinephrine