Comparison of Newer and Traditional Antiepileptic Drugs in the Treatment of Epilepsy Induced by MELAS

Levetiracetam, carbamazepine, and topiramate were equally safe and effective in the treatment of adult patients with epilepsy induced by the syndrome of mitochondrial encephalompathy, lactic acidosis, and stroke-like episodes (MELAS), but valproate was significantly less effective and associated with significantly more adverse events, according to research presented at the 65^th Annual Meeting of the American Academy of Neurology.

MELAS is a rare, neurodegenerative disorder that affects multiple body systems, including the neurological, muscular, endocrine, auditory, visual, cardiac, psychiatric, renal, gastrointestinal, and dermatological systems. It is caused by mutations in mitochondrial DNA, is polygenetic, and is inherited through the mother. Due to its varied range of symptoms, signs, and acute clinical presentations, it can be difficult to diagnose. Both convulsive and nonconvulsive status epilepticus have been reported in MELAS patients. Unfortunately, MELAS remains largely untreated, despite the fact that appropriate prevention and management of the medical complications of this disease may actually prolong survival. Further education is needed to build awareness of this syndrome and to help physicians determine which antiepileptic drugs may be useful in treating the epileptic features of this disease.

Xuewu Liu, MD, of Qilu Hospital and Shandong University, in Jinan, China, and colleagues conducted a 52-week, open-label, prospective, randomized, controlled, multicenter study involving 84 adult patients with MELAS (partial or secondary generalized epilepsy) that was designed to compare the efficacy of monotherapy with newer and traditional antiepileptic drugs and determine which is most effective. Newer drugs included levetiracetam (up to 2000 mg/day) and carbamazepine (up to 300 mg/day), and traditional agents studied included valproate (up to 1000 mg/day) and topiramate (up to 200 mg/day).

The study was designed to evaluate the superiority of traditional antiepileptic agents over newer agents, and the primary study endpoint was the rate of seizure-free patients in the first 12 weeks of treatment. Secondary efficacy, tolerability, and quality of life endpoints were also evaluated. During the 52-week treatment period, no significant differences were found between the proportions of seizure-free patients for levetiracetam, topiramate, and carbamazepine (57.1%, 42.9%, and 57.1%, respectively). However, only 4.8% of patients with MELAS treated with valproate were seizure-free.

With regard to safety, 5% (1/21), 14% (3/21), 0%, and 90% (19/21) of levetiracetam-, topiramate-, carbamazepine, and valproate patients, respectively, discontinued the study due to adverse events. Adverse events in the valproate group were also statistically significantly different from the other drugs, with no between-group difference for the other three agents. These data are in line with reports from other studies, which suggest that valproic acid can exacerbate seizures in these patients and precipitate stroke-like episodes, due to its detrimental effects on mitochondria.

"There were no significant differences with regard to efficacy and tolerability of levetiracetam, topiramate, and carbamazepine in newly diagnosed epilepsy induced by mitochondrial encephalomyopathy. But valproate should not be used to treat these patients because it had no effect and was associated with a series of side effects,” the authors concluded.