It's becoming clearer that some anti-epileptic drugs (AEDs) are better than others during pregnancy, with valproate probably the biggest no-no.
But recent studies, including one published this week, haven't yet added up to an algorithm for deciding which one is best for a given patient. For now, the decision still comes down to the individual clinician's judgment and the patient's tolerance for risk to herself and her unborn child.
The newest study, appearing , compared neurodevelopmental outcomes at ages 3 to 4 in 44 children born to women who took valproate, 53 exposed in utero to levetiracetam (Keppra), and 131 whose mothers were not epileptic and did not take AEDs.
Not surprisingly, in light of past studies, children with fetal exposure to valproate in utero showed significant language and motor skill impairments relative to the no-AED control group, reported Rebekah Shallcross, PhD, of the University of Liverpool in England, and colleagues.
Valproate already sports a Pregnancy Class D designation because it is known to increase risk of birth defects, and a prospective study from the found diminished IQ in 6-year-olds exposed to valproate in utero, relative to children of mothers who took other AEDs during pregnancy.
Of perhaps greater interest in the new study was a finding that no impairments of any kind were seen in the levetiracetam group compared with the control group. "The current research suggests levetiracetam may be a viable alternative [to valproate] for many women with epilepsy, in terms of the later development of the child," Shallcross and colleagues wrote.
But this study doesn't necessarily tell the whole tale. For one thing, it was partly funded by levetiracetam's manufacturer, UCB Pharma, which has also paid speaking fees to Shallcross. (Several other AED manufacturers also supported the study.) In addition, the study didn't address perinatal outcomes such as congenital defects, preterm birth, or low birth weight -- which have been found to accompany AEDs as a class when used during pregnancy.
An in Neurology by two researchers from the Mid-Atlantic Epilepsy and Sleep Center, Pavel Klein, MB, BChir, and Gregory Mathews, MD, PhD, also pointed out that the patient samples in the new study were small and differed from each other in important respects.
Klein and Mathews also argued that simply switching women from valproate to levetiracetam or another AED is not necessarily the best solution. Some women with epilepsy respond only to valproate, they indicated.
"In this relatively small but important group of women with refractory primary generalized epilepsy or symptomatic epilepsy with primary generalized seizures, the practitioner is challenged with the common dilemma of whether the potential benefit of treatment outweighs the potential harm of the medication. For refractory generalized seizures, the data are lacking to make an informed, rational choice," they wrote.
Also, a common alternative medication, lamotrigine, appears to increase the risk of generalized tonic-clonic seizures relative to other AEDs, Klein and Mathews said.
The bottom line appears to be to avoid valproate during pregnancy if seizures can be controlled with other drugs. But science doesn't yet offer much guidance on which other drug to use, or what to do in patients who don't respond to treatments other than valproate.
Striking a Nerve is a blog by John Gever for readers interested in neurology and psychiatry.