Circadian Variation in Efficacy of Medications

Clin Pharmacol Ther. 2021 Jun;109(6):1457-1488. doi: 10.1002/cpt.2073. Epub 2020 Nov 29.


Although much has been learned about circadian clocks and rhythms over the past few decades, translation of this foundational science underlying the temporal regulation of physiology and behavior to clinical applications has been slow. Indeed, acceptance of the modern study of circadian rhythms has been blunted because the phenomenology of cyclic changes had to counteract the 20th century dogma of homeostasis in the biological sciences and medicine. We are providing this review of clinical data to highlight the emerging awareness of circadian variation in efficacy of medications for physicians, clinicians, and pharmacists. We are suggesting that gold-standard double-blind clinical studies should be conducted to determine the best time of day for optimal effectiveness of medications; also, we suggest that time of day should be tracked and reported as an important biological variable in ongoing clinical studies hereafter. Furthermore, we emphasize that time of day is, and should be considered, a key biological variable in research design similar to sex. In common with biomedical research data that have been historically strongly skewed toward the male sex, most pharmaceutical data have been skewed toward morning dosing without strong evidence that this is the optimal time of efficacy.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Circadian Rhythm*
  • Clinical Trials as Topic
  • Drug Therapy*
  • Female
  • Humans
  • Male
  • Sex Characteristics