According to new research published in Epilepsia, the journal of the International League Against Epilepsy (ILAE), patients with epilepsy who were treated with older generation antiepileptic drugs (AEDs) for extended periods may be at increased risk for developing atherosclerosis, a common disorder known as hardening of the arteries. The study reveals that the vascular risk is substantially linked to the duration of AED monotherapy.

Even though the majority of epilepsy patients achieve good treatment results, over 30% of epilepsy patients continue to have seizures (refractory epilepsy) despite being on AED treatment. These patients require long-term or even lifelong AED therapy. However, prolonged treatment can lead to diabetes, thyroid issues, psychiatric problems and adverse drug reactions. Earlier studies suggest that older-generation AEDs, such as carbamazepine, phenytoin, phenobarbital, and valproic acid may change metabolic pathways and therefore contribute to higher vascular risks.

Lead author, Dr. Yao-Chung Chuang from Kaohsiung Chang Gung Memorial Hospital in Taiwan and his team decided to compare the long-term impact of different categories of AED monotherapy on atherosclerosis development, for which they enrolled 160 adult epileptic patients who had undergone AED monotherapy for over 2 years, together with 60 healthy controls. To measure participants’ common carotid artery (CCA) intima media thickness (IMT), the researchers used ultrasonography, a measure that evaluates the extent of atherosclerosis.

Dr. Chuang commented:

“Our study found patients with epilepsy who were under long-term monotherpy with phenytoin, carbamazepine and valproic acid displayed significantly increased CCA IMT measurements. These altered circulatory markers from prolonged AED therapy may accelerate the atherosclerotic process.”

The findings of the study demonstrated a positive correlation between CCA IMT and the duration of AED therapy.

In addition, the researchers also examined particular vascular risk factors linked to types of AED therapy. They discovered that epilepsy patients, who were receiving carbamazepine or phenytoin therapy for extended periods of time displayed increased cholesterol- and amino acid-levels, total homocysteine (tHcy), as well as decreased levels of folate; All of these increase the risk of adverse cardiovascular and cerebrovascular events. Those treated with valproic acid showed elevated levels of uric acid, tHcy, and thiobarbituric acid reactive substances (TBARS) that increase the risk of atherosclerosis, which the authors suggest may be based on oxidative mechanisms.

The authors’ stress that drug choice for epilepsy patients in need of long-term AED therapy must be carefully selected, especially in elderly patients or those at high-risk of vascular events.

Lead researcher Dr. Chuang summarized:

“Our findings suggest that newer AEDs, such as lamotrigine, may minimize metabolic disturbances, and therefore reduce the risk of atherosclerosis brought on by long-term AED therapy.”

Written by Petra Rattue