College of Pharmacy Associate Professor Xuerong Wen links losartan to lower incidence of epilepsy

Nearly half of all adults in the U.S. have been diagnosed with hypertension, according to the Centers for Disease Control and Prevention, many of whom are also at risk of epilepsy. Of the several types of antihypertension medications patients are prescribed, one of the most common is associated with a lower risk of epilepsy, according to a recently published study by a University of Rhode Island College of Pharmacy professor.

Associate Professor Xuerong Wen led a study of data from more than 2 million patients with hypertension who had been prescribed medication—either angiotensin receptor blockers, angiotensin-converting enzyme inhibitors, beta-blockers, or calcium channel blockers. Her findings show patients with no preexisting stroke or cardiovascular disease who took ARBs—particularly the drug losartan—had a significantly lower risk of epilepsy.

“The findings of this demonstrated that ARBs, mainly losartan, may be associated with a lower incidence of epilepsy compared with ACEIs, beta-blockers, and CCBs,” Wen said. “People with hypertension often have other comorbidities, so physicians need to evaluate baseline risk due to the wide variety of available hypertension medications. Losartan so far has shown it has an advantage of lowering the risk of epilepsy.”

The study, which was published in JAMA Neurology in June, included more than 2 million individuals who took some form of antihypertension medication, including ARBs like losartan. Wen’s Ph.D. student, Marianne Otoo, conducted data analyses, while several URI clinical pharmacy faculty members—including Kristina Ward, Todd Brothers, and Nicole Asal—contributed significantly to the study design, results interpretation, manuscript writing and clinical implication. The URI-based multidisciplinary research team also included Dr. Jie Tang, a nephrologist from Brown Medicine, who helped discuss the mechanisms of losartan and epilepsy, and Dr. Kimford Meador, a well-known neurologist from Stanford Medicine, who initiated the research question and guided the project.  

Many of those patients are also at risk of epilepsy, which can be caused by brain injury, including a stroke or microvascular trauma, in which central nervous system cells known as astrocytes malfunction and can cause inflammation, often resulting in seizures. Even patients without diagnosed epilepsy can be subject to seizures when the blood brain barrier is disrupted. Losartan has been shown to block astrocyte activation and reduce blood brain barrier damage, thus, lowering the risk of epilepsy.

After investigating all forms of antihypertension medications, including several forms of ARBs, Wen’s team found losartan was the only medication that consistently showed lower epilepsy incidence among patients. Whether that means losartan can be used specifically to prevent epilepsy—beyond it being a side benefit of treating hypertension—needs further research.

“Dr. Meador considering a further clinical trial to find out if losartan can prevent epilepsy,” Wen said. “Many physicians are very excited to do a clinical trial to demonstrate that it can prevent epilepsy. It is optimistic, but needs further work.”