Effects of Circadian Rhythm on Migraine Therapy

Abstract

Circadian rhythms are 24-hour cycles of physical, mental, and behavioral changes regulated and maintained by the internal primary circadian clock, however modifiable by a number of external cues or “zeitgebers”, the most powerful one being light. Core set of clock genes regulate the whole-body metabolism and transcription of over 40% of mammalian RNA, including that for drug transporters, binding and metabolizing proteins responsible for regulation of pharmacokinetics of vast array of medications. Growing amount of evidence also shows circadian rhythmicity of a number of patho-physiological processes, such as are migraine, chronic pain, and epilepsy, suggesting amenability to chronotherapy. Chronotherapy involves behavioral and pharmacological strategies to restore or correct ill-functioning circadian rhythm as well as manipulation of standardized treatments throughout the day to maximize therapeutic and minimize side effects, termed chronopharmacology. Chronotherapy for chronic migraines and headache variants using synchronization techniques as well as chronopharmacology of abortive and preventive migraine medications is being actively researched. In this review, we summarize current state of chronotherapy for headache variants and discuss future prospects in circadian optimization of migraine headaches treatment.