Chronopharmacology of anti-convulsive therapy

Curr Neurol Neurosci Rep. 2013 Apr;13(4):339. doi: 10.1007/s11910-013-0339-2.


Approximately one-third of patients with epilepsy continue to have seizures despite antiepileptic therapy. Many seizures occur in diurnal, sleep/wake, circadian, or even monthly patterns. The relationship between biomarkers and state changes is still being investigated, but early results suggest that some of these patterns may be related to endogenous circadian patterns whereas others may be related to wakefulness and sleep or both. Chronotherapy, the application of treatment at times of greatest seizure susceptibility, is a technique that may optimize seizure control in selected patients. It may be used in the form of differential dosing, as preparations designed to deliver sustained or pulsatile drug delivery or in the form of 'zeitgebers' that shift endogenous rhythms. Early trials in epilepsy suggest that chronopharmacology may provide improved seizure control compared with conventional treatment in some patients. The present article reviews chronopharmacology in the treatment of epilepsy as well as future treatment avenues.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Abnormalities, Drug-Induced / physiopathology
  • Abnormalities, Drug-Induced / prevention & control
  • Adult
  • Animals
  • Anticonvulsants / administration & dosage*
  • Anticonvulsants / adverse effects
  • Anticonvulsants / pharmacokinetics
  • Biotransformation
  • Body Temperature
  • Child
  • Circadian Rhythm / physiology
  • Drug Chronotherapy*
  • Drug Delivery Systems
  • Epilepsy / drug therapy
  • Epilepsy / physiopathology
  • Epilepsy / prevention & control
  • Epilepsy / therapy
  • Food-Drug Interactions
  • Gene Expression Regulation
  • Humans
  • Hydrocortisone / metabolism
  • Intestinal Absorption
  • Melatonin / metabolism
  • Melatonin / therapeutic use
  • Mice
  • Phototherapy
  • Prospective Studies
  • Randomized Controlled Trials as Topic
  • Retrospective Studies
  • Sleep Stages / physiology


  • Anticonvulsants
  • Melatonin
  • Hydrocortisone