It's About Time: Can Chronotherapy Improve Epilepsy Treatment?


Adjusting the timing of antiepileptic drug administration has the potential to help improve efficacy.

Adjusting the timing of antiepileptic drug administration has the potential to help improve efficacy.

Chronotherapy—modifying medication timing with respect to disease changes related to circadian rhythm—can maximize drug efficacy and minimize adverse effects. We already use chronotherapy in a number of ways: administering medications at the times when they deliver the most effective drug levels; timing drug troughs to lowest-risk hours; and administering doses so side effects occur at the least intrusive times. In epilepsy patients, chronotherapy may help reduce the number of seizures that persist despite chronic use of antiepileptic drugs (AEDs). For the more than 30% of patients who continue to have seizures even when AED-adherent, this approach may help offer some relief.

Researchers have identified several seizure patterns that appear time-related and are investigating the relationship between biomarkers and central nervous system changes. Seizures frequently occur in diurnal, sleep/wake, circadian, seasonal, or monthly patterns. To date, researchers have linked these patterns to endogenous circadian patterns and/or wakefulness/sleep cycles. Endogenous rhythms alter AED digestion, absorption, distribution, metabolism, and excretion. AEDs themselves can modify circadian, diurnal, or wake/sleep patterns. Early trials suggest some epileptic patients may have improved seizure control if their conventional treatment is shifted to chronopharmacology.

A review article in the April 2013 edition of Current Neurology and Neuroscience Reports discusses this topic and describes the best ways to pinpoint seizure patterns and determine whether chronotherapy is a rational option. The authors discuss many unique characteristics of AEDs that may cause, contribute to, or address chronologic seizure variations. They also look at other mechanisms with the potential to address seizure variations, including light therapy and melatonin levels.

The authors discuss several ways to administer AEDs to create patient-specific chronotherapy. Their coverage of manual and electronic seizure diaries provides information on how to identify patterns. Although this science is in its infancy, chronotherapy may offer relief to patients who have determined that they have rhythmic breakthrough seizures. New dosing strategies or short-term supplemental use of an additional AED may help.

Ms. Wick is a visiting professor at the University of Connecticut School of Pharmacy and a freelance writer from Virginia.

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