Benefit of combination therapy in epilepsy: A review of the preclinical evidence with levetiracetam
Version of Record online: 10 JUL 2008
Wiley Periodicals, Inc. © 2008 International League Against Epilepsy
Volume 50, Issue 3, pages 387–397, March 2009
How to Cite
Kaminski, R. M., Matagne, A., Patsalos, P. N. and Klitgaard, H. (2009), Benefit of combination therapy in epilepsy: A review of the preclinical evidence with levetiracetam. Epilepsia, 50: 387–397. doi: 10.1111/j.1528-1167.2008.01713.x
- Issue online: 4 MAR 2009
- Version of Record online: 10 JUL 2008
- Accepted May 9, 2008; Early view publication July 10, 2008.
- Levetiracetam, Antiepileptic drugs, Drug interactions, Epilepsy, Animal models.
Levetiracetam (Keppra) is an antiepileptic drug (AED) characterized by a novel mechanism of action, unique profile of activity in seizure models, and broad-spectrum clinical efficacy. The present report critically reviews several preclinical studies focused on combination therapy with levetiracetam and other anticonvulsants in various seizure and epilepsy models. Administration of levetiracetam together with many different clinically used AEDs or other anticonvulsants generally enhances their protective activity and, among existing AEDs, this was particularly prevalent with valproate. The protective activity of other AEDs was also enhanced by levetiracetam, which seems to be a universal finding that is independent of seizure model or drug combination studied. However, particularly strong enhancement was observed when levetiracetam was combined with agents either enhancing GABAergic or reducing glutamatergic neurotransmission. Importantly, these combinations were not associated with exacerbation of side effects or pharmacokinetic interactions. Based on the available preclinical data, it appears that combination treatment with levetiracetam and other anticonvulsants provides additional therapeutic benefit that may be attributed to its novel and distinct mechanism of action. Moreover, combinations of levetiracetam with clinically used AEDs that enhance GABAergic inhibition may be considered for rational polytherapy, which is often necessary in drug-resistant patients.