Circadian attributes of neurological and psychiatric disorders as basis for their medication chronotherapy

Abstract

This review focuses on (i) 24 h patterns in the symptom intensity of common neurologic and psychiatric disorders and (ii) medications prescribed for their management that have a recommended administration time or schedule, presumably to potentiate desired and minimize undesired effects and by definition qualify them as chronotherapies. Predictable-in-time patterning of symptoms is exhibited by many neurologic -- headaches, multiple sclerosis, neurogenic orthostatic hypotension, neuropathic pain, Parkinson's disease, epileptic seizure, attention deficit hyperactivity, Alzheimer's disease - and psychiatric - eating, depressive, obsessive-compulsive, post-traumatic stress, anxiety, and panic - disorders, due either to circadian rhythms of disease pathophysiology or inadequacies of medication-delivery systems. Circadian disruption and circadian misalignment of the sleep-wake and other 24 h rhythms plus late chronotype are characteristic of many of these disorders, suggesting involvement in the mechanisms or consequence of their pathology or as an adverse effect of therapy, especially when administered at an inappropriate biological time. The Prescribers' Digital Reference, a compendium of all prescription medications approved for marketing in the US, reveals 65 of them are utilized to manage neurologic and psychiatric disorders by a specified time-of-day or an asymmetrical interval or strength of dose schedule, presumably to optimize beneficial and minimize adverse effects, thereby qualifying them as chronotherapies. Overall, the contents of this review are intended to inform the development of future chronotherapies that incorporate state-of-the-art drug-delivery systems to improve management of neurologic and psychiatric disorders and associated circadian malalignment and disruption.

Keywords: Chronotherapeutics; Chronotype; Circadian disruption; Circadian misalignment; Circadian rhythms; Neurologic disorders; Psychiatric disorders; Time-of-day patterns.