title: Is a separate monotherapy indication warranted for antiepileptic drugs?
abstract: Antiepileptic drugs (AEDs) are the only neurotherapeutics for which regulatory approval is consistently separated into monotherapy or adjunctive-therapy indications. Because head-to-head comparisons of AEDs (used in the European Union to approve drugs for monotherapy) have not shown substantial differences in efficacy between drugs, FDA approval for use of an AED as monotherapy has typically been based on trials with novel designs that have been criticised for reasons of ethics and clinical relevance. Many new-generation AEDs have not been approved for monotherapy, causing drug labelling and real-world use to be increasingly inconsistent, with negative consequences for patients. The regulatory requirement for separate monotherapy and adjunctive-therapy indications in epilepsy is unnecessarily restrictive. We recommend that regulatory agencies approve AEDs for the treatment of specific seizure types or epilepsy syndromes, irrespective of concomitant drug use.
authors.affiliation: Thomas Jefferson University, Philadelphia, PA, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Mintzer
authors.affiliation: NYU Langone School of Medicine, New York, NY, USA. Electronic address: jacqueline.french@nyumc.org.
authors.forename: Jacqueline A
authors.initials: JA
authors.lastname: French
authors.affiliation: University of Pavia and C. Mondino National Neurological Institute, Pavia, Italy.
authors.forename: Emilio
authors.initials: E
authors.lastname: Perucca
authors.affiliation: Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Joyce A
authors.initials: JA
authors.lastname: Cramer
authors.affiliation: Retired, Moncure, NC, USA.
authors.forename: John A
authors.initials: JA
authors.lastname: Messenheimer
authors.affiliation: Sunovion Pharmaceuticals, Marlborough, MA, USA.
authors.forename: David E
authors.initials: DE
authors.lastname: Blum
authors.affiliation: University of California, Davis, Sacramento, CA, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Rogawski
authors.affiliation: Department of Neurology, Hôpital Pitié-Salpêtriére, Paris, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Baulac
mesh_terms: D000927:Anticonvulsants / Q000627:therapeutic use*; D017277:Drug Approval; D004359:Drug Therapy, Combination; D004827:Epilepsy / Q000188:drug therapy*; D006801:Humans
chemical_list: D000927:Anticonvulsants