Is it time to think about chronotherapy in migraine.

Migraine is among the most dynamic and disabling neurological disorders, affecting over one billion people globally. Attacks demonstrate rhythmic patterns of onset across the day and seasonally, highlighting that attack onset is influenced by an individual's biological rhythms. Indeed, an individual's chronotype (their endogenous circadian clock rhythm) predicts when they are most likely to have an attack. These biological rhythms are regulated by an endogenous master biological clock in the hypothalamus that coordinates the function of peripheral clocks, aligning biological processes and behaviours to environmental cues (e.g. daily rhythms in light-dark cycles). As such, circadian rhythms are essential to maintain normal neurological function and health, regulating the expression of approximately 50 % of all protein coding genes in mammals. Importantly, the majority of the World Health Organisations essential medicines and several migraine-related therapeutics directly target the products of these rhythmic genes or influence circadian-related genes directly. Therefore, the current review will focus on the potential for chronotherapy in migraine. Highlighting its potential to optimise the chronopharmacokinetic profile, therapeutic efficacy and reduce potential side effects of anti-migraine therapies. A greater understanding of which has the potential for significant impact, representing a low cost, scalable method to improve therapeutic response and inform a personalized therapeutic strategy.