In the May 1, 2012 issue of the journal, Neurology, Drs. Kraus and colleagues, from an international multi-center investigation group, present results regarding a new medication with a novel mechanism of action named perampanel. Perampanel works as a selective, non-competitive AMPA receptor antagonist. In this particular study which was a double-blind, placebo controlled trial, patients with persisting seizures on up to three anti-seizure drugs were sorted into one of 4 treatment groups; perampanel 2, 4, and 8 mg per day or a placebo following a 6-week baseline period. Perampanel was titrated weekly by 2 mg per day and maintained at the dose achieved for 13 weeks. The primary endpoints were the change in seizure frequencies compared to baseline and a 50% responder rate which is the number of individuals who had a decrease in the number of their seizures by 50%. The seizures were noted on a diary.

Seven hundred six patients were randomized and received the medication. Of which 623 individuals were able to complete the trial. The percent change in seizure frequency was 10% reduction at 2 mg a day; 13.6% reduction at 4 mg a day; and 30.8 % reduction for 8 mg a day. This difference from placebo was significant for perampanel 4 mg a day and 8 mg per day. The corresponding 50% responder rates were 17.9, 20.6, 28.5, and 34.9. The difference from placebo was significant for perampanel 4 mg per day and 8 mg per day. Dizziness was the most common side effect related to the medication.

The trial demonstrated that perampanel, when added to other seizure drugs in patients with partial seizures, effectively reduced seizure frequency and possessed a favorable profile in patients who are older than 12 years with partial onset seizures with a minimum effective dose of 4 mg per day. The authors went on to conclude that the study provides class one evidence that 4 and 8 mg per day doses of adjunctive perampanel are effective and tolerated in reducing partial onset seizures.

This study is particularly important primarily because it represents a new medication with a new mechanism of action. The drug reduced seizures at a minimum of 4 mg dose to 8 mg per day. The side effects that were primarily noted included dizziness but other side effects mentioned in the study included somnolence, headache, and tiredness.

This is another promising medication that works via a unique mechanism. It does bring up the possibility that combining it with another medication that works by a different mechanism could potentially be beneficial. This study did not specifically address this but it does bring up the possibility and hope for the future that this indeed may be the case. This study is also important because it helps to highlight the ever increasing number of treatment options and mechanisms by which we continue to target epilepsy. Only time will tell whether this drug becomes a first line choice for management of patients with partial seizures.

by Joseph I. Sirven, MD
Editor-in-Chief, epilepsy.com
Last Reviewed: 7/25/2012