Targeted Dosing

April 23, 2012  The Wall Street Journal

Treating Epileptic Seizures in Kids by the Clock

Neurologist Develops Individualized Plans for Patients Who Don't Respond to Conventional Drug Therapies

By Dawn Fallik

Tobias Loddenkemper, a pediatric neurologist, works with some of the hardest epilepsy cases—the children whose seizures have been little helped by medication or surgery.

Nearly a third of epilepsy patients don't get sufficient relief from conventional drug treatments. But where advanced techniques don't help, Dr. Loddenkemper hopes a simple solution might: timing patients' medication to better coincide with their seizures.

Epilepsy, which affects 1% of the U.S. population, is a seizure disorder involving a surge of electricity in the brain. Its cause often isn't known, but in children the condition may be congenital or the result of a head injury. When medications can't control seizures, alternative treatments may be attempted, including surgery, strict diets and brain-stimulation techniques. But these have had limited success, according to the Epilepsy Foundation, a patient-advocacy group.

Dr. Loddenkemper, who works at Children's Hospital in Boston, is trying ways to make medication more effective by adjusting dosages based on when a person's seizures typically occur. This month the 39-year-old won the American Academy of Neurology's Dreifuss-Penry Epilepsy Award for young researchers for his work on treatment approaches.

Dr. Loddenkemper's approach seems basic. He asked his patients, or their parents, to keep seizure diaries, a standard practice. From those diaries, he noticed many patients had seizures around the same time every day, but often took the same dose of medication throughout the day. He changed their medication schedule so they took a higher dose when they most frequently had seizures.

"Why give the medication in the morning if the patient isn't having seizures then?" he says. "If they are having more seizures at night, give it to them at night." Although targeted dosing isn't new, "it's slowly growing" as a common treatment, he says. There has also been very little research on its effectiveness.

In a small study published last year in the journal Epilepsy & Behavior, Dr. Loddenkemper and several colleagues at Children's Hospital looked at 17 children who had seizures at night or in the early morning. The researchers varied the patients' doses to administer more of their anti-seizure medication when episodes were more likely to occur, while leaving the total dosage unchanged. After five months, 15 of the patients saw their seizures reduced by more than half, and 11 had become seizure-free.

Elaine Wirrell, director of pediatric epilepsy at the Mayo Clinic in Rochester, Minn., who wasn't involved in the Children's Hospital research, said targeted dosing is sometimes tried if patients have a predilection for seizures at a specific time.

"It's not something that's usually in textbooks," she says. Having studies on the practice "legitimizes the practice and encourages it."

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Bertrand's big night seizures occur like clockwork sometime between 11:30-12:30am and 2:30-3:30am, (and occasionally between 5:30-6:30am) every night.  

Since we've heard NOTHING back from the neurology department, today we began the technique discussed in the article above (and in more detail in "Higher evening antiepileptic drug dose for nocturnal and early-morning seizures." Epilepsy Behav. 2011 Feb;20(2):334-7. Epub 2010 Dec 30. [PMID: 21195032]). 

Bertrand is shifting from 250mg of depakote at 7am and 5:30pm to 125mg of depakote at 7am, 125mg at 5:30pm, and 250mg at 10:00pm. So far, he was very alert and happy with no increase in daytime seizure activity. Fingers crossed for tonight.