title: Does the choice of antiepileptic drug affect survival in glioblastoma patients?
abstract: Patients with glioblastoma (GBM) often suffer from symptomatic epilepsy. Older antiepileptic drugs (AEDs) which affect the enzyme system cytochrome P450 have been in extensive use, but there is an increasing focus on interactions with other drugs. This study investigated whether newer AEDs with little or no enzyme effect are increasingly preferred. Previous research has indicated that valproate improves survival in GBM. We investigated the impact of AEDs on overall survival in GBM patients. All GBM patients diagnosed in Norway 2004-2010 were included through a linkage of national registries, and follow-up data on the malignancy and drug usage were analyzed. In a multivariate cox proportional-hazards regression, AEDs were adjusted for each other and for relevant factors. Immortal time bias was eliminated with time-dependent variables. The study population was 1263 patients with histologically confirmed GBM. Carbamazepine was the most frequently prescribed AED to patients diagnosed with GBM during 2004-2006, while levetiracetam was increasingly prescribed to patients diagnosed later. Taking AEDs on a reimbursement code of epilepsy was not beneficial for survival. None of the six AEDs valproate, levetiracetam, carbamazepine, oxcarbazepine, lamotrigine or phenytoin significantly altered overall survival. There has been a shift in the prescriptions of AEDs to GBM patients from older to newer AEDs over time. We found no significant survival benefit in GBM patients neither from treatment with AEDs for epilepsy in general, nor from the usage of six separate AEDs.
authors.affiliation: Department of Neurology, Haukeland University Hospital, Jonas Lies vei 65, 5021, Bergen, Norway. kristinmkb@hotmail.com.|Department of Clinical Medicine 1, University of Bergen, 5021, Bergen, Norway. kristinmkb@hotmail.com.
authors.forename: Kristin M
authors.initials: KM
authors.lastname: Knudsen-Baas
authors.affiliation: Department of Pharmacoepidemiology, Domain of Mental and Physical Health, Norwegian Institute of Public Health, 5020, Bergen, Norway.|Department of Global Public Health and Primary Care, University of Bergen, 5020, Bergen, Norway.
authors.forename: Anders
authors.initials: A
authors.lastname: Engeland
authors.affiliation: Department of Neurology, Haukeland University Hospital, Jonas Lies vei 65, 5021, Bergen, Norway.|Department of Clinical Medicine 1, University of Bergen, 5021, Bergen, Norway.
authors.forename: Nils Erik
authors.initials: NE
authors.lastname: Gilhus
authors.affiliation: Department of Neurology, Haukeland University Hospital, Jonas Lies vei 65, 5021, Bergen, Norway.|Department of Clinical Medicine 1, University of Bergen, 5021, Bergen, Norway.
authors.forename: Anette M
authors.initials: AM
authors.lastname: Storstein
authors.affiliation: Department of Neurology, Haukeland University Hospital, Jonas Lies vei 65, 5021, Bergen, Norway.
authors.forename: Jone F
authors.initials: JF
authors.lastname: Owe
mesh_terms: D000293:Adolescent; D000328:Adult; D017677:Age Distribution; D000368:Aged; D000927:Anticonvulsants / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000150:complications / Q000188:drug therapy / Q000401:mortality; D002648:Child; D002675:Child, Preschool; D004827:Epilepsy / Q000188:drug therapy* / Q000209:etiology*; D005260:Female; D005909:Glioblastoma / Q000150:complications / Q000188:drug therapy / Q000401:mortality; D006801:Humans; D007223:Infant; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009664:Norway / Q000453:epidemiology; D016016:Proportional Hazards Models; D012042:Registries; D012189:Retrospective Studies; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000927:Anticonvulsants
keywords: Antiepileptic drugs; Epilepsy; Glioblastoma; National registries; Overall survival