March 4, 2010 -- One of the oldest drugs used to treat the most common form of pediatric epilepsy is also the most effective, a study shows.
As many as 17% of children with epilepsy have absence seizures, also known as petit mal seizures, which involve brief but frequent staring spells that can occur dozens or even hundreds of times a day.
These children do not have the convulsions typically associated with epilepsy, but they are at high risk for developing them later in life.
During the 10- to 15-second seizure episodes, people with absence epilepsy become unresponsive and may stop walking or talking in mid-sentence. Children with these seizures often perform poorly in school.
The anticonvulsant drugs ethosuximide (Zarontin), valproic acid (Depakote, Depakene), and lamotrigine (Lamictal) are all used to treat the disorder, but there is no consensus on which drug is best for the initial treatment of children experiencing absence seizures.
"One reason we started this study was that we saw regional differences in how absence epilepsy was being treated," study researcher Tracy A. Glauser, MD, of Cincinnati Children's Hospital, tells WebMD. "These medications have different side effect profiles, and it wasn't at all clear which one was the best drug to start with."
Zarontin the 'Clear Winner'
Glauser and colleagues conducted a trial to compare the effectiveness and side effects of the three drugs in children with absence epilepsy who had received no prior treatment.
Their findings appear in the March 4 issue of the New England Journal of Medicine.
The trial was conducted at 32 sites across the U.S.; it included 156 children initially treated with Zarontin, 149 treated with Lamictal, and 148 treated with Depakote.
Zarontin, used since the late 1950s, is the oldest and cheapest of the three drugs, and the only one used exclusively for the treatment of absence epilepsy.
Depakote was introduced several years later and is also used to treat other seizure disorders, bipolar disorder, and migraines.
Approved for the treatment of seizures in 1994, Lamictal is the newest of the drugs. It is also used to treat bipolar disorder and is being studied for the treatment of migraines.
In the newly published study, Lamictal was found to be significantly less effective than Zarontin or Depakote for preventing absence seizures, while treatment with Depakote was more likely to result in concentration problems than treatment with the other two drugs.
Concentration and attention issues are among the most troubling side effects of treatment for absence seizures.
"When we considered seizure control and the effect on attention, [Zarontin] was the clear winner," Glauser says. "All things being equal, this drug should be considered the first-line treatment for children with absence epilepsy."
Study co-author Shlomo Shinnar, MD, PhD, of New York's Montefiore Medical Center, agrees.
"Unless there are reasons not to use it, Zarontin would certainly be my first-line choice," he says.
Half of Patients Failed Treatment
But it may not be the treatment many children with the disorder end up on.
Glauser points out that about half the children in the study continued to have seizures 16 to 20 weeks after starting treatment. While the treatment failure rate was highest for those taking Lamictal, it was also high in children who took the other two drugs.
"One clear message is that if a drug is not working after four or five months, it is time to move on to another drug," he says.
In an editorial accompanying the study, pediatric neurologist Eileen Vining, MD, of Baltimore's Johns Hopkins University School of Medicine, wrote that a longer study would have more convincingly made the case that Zarontin is the best initial choice for the treatment of absence epilepsy.
While Vining praised the study's design and execution, she noted that this may not be the case for children at high risk for developing convulsive seizures, which are treated with Lamictal and Depakote but not Zarontin.
GlaxoSmithKline, which markets Lamictal, had no comment on the study.