Public release date: 11-May-2012 [ | E-mail | Share ]
Contact: Karen Mallet km463@georgetown.edu Georgetown University Medical Center
WASHINGTON -- A brain study in infant rats demonstrates that the anti-epilepsy drug phenobarbital stunts neuronal growth, which could prompt new questions about using the first-line drug to treat epilepsy in human newborns.
In Annals of Neurology EarlyView posted online May 11, researchers at Georgetown University Medical Center (GUMC) report that the anti-epilepsy drug phenobarbital given to rat pups about a week old changed the way the animals' brains were wired, causing cognitive abnormalities later in life.
The researchers say it has been known that some of the drugs used to treat epilepsy increase the amount of neurons that die shortly after birth in the rat brain, but, until this study, no one had shown whether this action had any adverse impact on subsequent brain development.
"Our study is the first to show that the exposure to these drugs -- and just a single exposure -- can prevent brain circuits from developing their normal connectivity, meaning they may not be wired correctly, which can have long-lasting effects on brain function," says the study's senior investigator, Karen Gale, Ph.D., a professor of pharmacology at GUMC. "These findings suggest that in the growing brain, these drugs are not as benign as one would like to believe."
For their study, the Georgetown researchers studied four agents including phenobarbital.
"The good news is not all anti-epilepsy drugs have this disruptive effect in the animal studies," Gale says.
The researchers found that the anti-epilepsy drug levetiracetam did not stunt synaptic growth. Animals treated with a third drug, lamotrigine, showed neural maturation, but it was delayed. An additional finding involved melatonin. When added to phenobarbital, it appeared to prevent the persistent adverse neural effects in the rat pups. Melatonin has been used clinically to protect cells from injury in humans.
"Many clinicians have been advocating for a reexamination of the use of these drugs in infants, and our findings provide experimental data to support that need," says the study's co-lead investigator, Patrick A. Forcelli, Ph.D., a postdoctoral fellow in the department of pharmacology and physiology at GUMC. "Phenobarbital has been used to treat seizures for over 100 years -- well before a Food and Drug Administration approval process was established-- and for more than 50 years, it has been the first drug of choice in the treatment of seizures in neonates."
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Study raises questions about use of anti-epilepsy drugs in newborns