Drug Combination Effectively Treats Refractory Epilepsy

The combination of two widely used drugs—lamotrigine and valproate—may treat refractory epilepsy more effectively than other antiepileptic regimens, researchers at the University of Washington have found.

The researchers, led by Nicholas P. Poolos, MD, PhD, a University of Washington associate professor of neurology, conducted a large-scale, retrospective study of 148 developmentally disabled patients with highly refractory epilepsy who were cared for in two state-run institutions.

Using records from the institutions that tracked the patients’ monthly convulsive seizure occurrence and antiepileptic drug (AED) regimens for over 30 years, the researchers studied how seizure frequency was affected by eight frequently prescribed AEDs—both alone and in combination.

They found that, out of 32 different drug regimens, the combination of lamotrigine and valproate was the only one to significantly decrease seizure frequency. On average, the combination cut seizure frequency in half compared with the other regimens studied. However, the researchers wrote in the study abstract that a combination of three AEDs “provided no further benefit over two.”

Roughly a third of the three million Americans with epilepsy suffer from a refractory, or drug-resistant, form of the condition and are forced to try a series of drug combinations in search of one that will work. New information on which combinations are most effective has the potential to reduce the frustration currently experienced by these patients and their doctors.

"The study results dispel the dogma that all drug treatments are equally ineffective for this patient population and provide evidence for future, prospective drug trials," Poolos said in a press release on the study from the University of Washington.

Since the study was limited by its retrospective design, lack of randomization, and small sample of some drug combinations, the researchers suggested that future studies be performed to confirm their findings, preferably in a prospective study of patients with refractory epilepsy from the general population.

The study appears in the January 3 edition of Neurology.