When It Comes to Sedation, Antiepileptics Not Created Equal


MIAMI BEACH – Some antiepileptic drugs cause more sedation than do others, according to a study presented at the annual meeting of the American Academy of Neurology.

Sedation is a common side effect of antiepileptic drugs (AEDs). However, the relative prevalence of sedation associated with each AED is unknown, David B. Weintraub said.

Mr. Weintraub and his associates performed a head-to-head comparison of epilepsy drugs commonly used at the Columbia Comprehensive Epilepsy Center at New York-Presbyterian Hospital in New York City, where he is a research coordinator.

Researchers reviewed charts for 1,088 adult patients treated at the center since January 2001. They assessed the overall rate of sedation attributed to a particular AED and whether sedation led to drug discontinuation.

They also looked at subpopulations taking an AED as monotherapy and patients beginning a particular agent, or “new starts.” In each comparison, the drug was compared with the average rate of sedation of all other agents using chi-square analysis.

Investigators reviewed the Columbia AED database for patients' background, medical history, and AED use, including AED efficacy and side effects.

In addition, the investigators recorded all physician or patient reports of sedation or sleepiness, tiredness, lethargy, drowsiness, or fatigue associated with an AED.

Overall, 34% of the participants experienced sedation from one or more AEDs. An average of 15% of patients starting a new AED experienced sedation. In almost 5% of participants, the sedation was cited as a reason the patient discontinued the drug.

Elan, GlaxoSmithKline, Pfizer, Ortho-McNeill, and UCB Pharma provide funding for the Columbia AED database. Mr. Weintraub has received financial support from UCB Pharma.

The incidence of both sedation and drug discontinuation were highest among patients taking phenobarbital (39% and 15%, respectively). Phenytoin had a higher than average incidence of sedation (32%), as did levetiracetam (20%), but discontinuation rates among patients taking these drugs were average.

“Phenytoin and levetiracetam were the only ones that reached statistical significance for increasing sedation,” coauthor and presenter Lawrence J. Hirsch, M.D., said. (The 13 patients taking phenobarbital in the study were too few to reach statistical significance.)

Dr. Hirsch, of the department of neurology at Columbia University, has received personal compensation from Elan, GlaxoSmithKline, Ortho-McNeil, and UCB Pharma; he has also received financial support from these four companies as well as from Pfizer.

Intermediate rates of sedation were associated with oxcarbazepine (17%), zonisamide (16%), topiramate (14%), carbamazepine (13%), clobazam (13%), and valproic acid (11%).

The researchers found that lamotrigine (10%) and gabapentin (9%) had the lowest consistent sedating effects in the study.

The investigators also looked at the 254 patients taking an AED as monotherapy. The average rate of sedation was 21% in this subpopulation.

“These were smaller numbers,” Dr. Hirsch said. “Nothing reached statistical significance here.”

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