title: Do antiepileptic drugs or generalized tonic-clonic seizure frequency increase SUDEP risk? A combined analysis.
abstract: OBJECTIVE
  In an analysis of four case-control studies of sudden unexpected death in epilepsy (SUDEP), we found that yearly frequency of generalized tonic-clonic seizures (GTCS) and antiepileptic drug (AED) polytherapy were associated with an increased risk for SUDEP. The prior analysis, however, did not evaluate AEDs and GTCS frequency concurrently.
  
  
  METHODS
  We combined data from the three case-control studies with information on the frequency of GTCS and AED therapy, that is, carbamazepine, phenytoin, valproic acid, and other AED therapy. Number of AEDs was also considered. Lamotrigine and GTCS frequency were considered separately in two of the case-control studies. Logistic regression analysis was used to evaluate GTCS frequency, each of the AEDs, and number of AEDs. Adjusted analysis of the different AEDs accounted for study, age at death, gender, and GTCS frequency.
  
  
  RESULTS
  In crude analysis, GTCS frequency, AED polytherapy, and number of AEDs were associated with an increased risk for SUDEP. Analysis of individual AEDs and of number of AEDs, adjusting for GTCS frequency, revealed no increased risk associated with AEDs as monotherapy, polytherapy, or total number. GTCS frequency remained strongly associated with an increased risk for SUDEP.
  
  
  CONCLUSIONS
  Our findings-that none of the AEDs considered were associated with increased SUDEP risk as monotherapy or as polytherapy when GTCS frequency was taken into account-provide a consistent message that number of GTCS increases SUDEP risk and not AEDs. These results suggest that prevention of SUDEP must involve increased efforts to decrease GTCS frequency in order to avert the occurrence of this devastating epilepsy outcome.
authors.affiliation: Department of Epidemiology, GH Sergievsky Center, Columbia University, New York, New York 10032, USA. dch5@columbia.edu
authors.forename: Dale C
authors.initials: DC
authors.lastname: Hesdorffer
authors.forename: Torbjorn
authors.initials: T
authors.lastname: Tomson
authors.forename: Emma
authors.initials: E
authors.lastname: Benn
authors.forename: Josemir W
authors.initials: JW
authors.lastname: Sander
authors.forename: Lena
authors.initials: L
authors.lastname: Nilsson
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Langan
authors.forename: Thaddeus S
authors.initials: TS
authors.lastname: Walczak
authors.forename: Ettore
authors.initials: E
authors.lastname: Beghi
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Brodie
authors.forename: W Allen
authors.initials: WA
authors.lastname: Hauser
mesh_terms: D000927:Anticonvulsants / Q000009:adverse effects*; D016022:Case-Control Studies; D003645:Death, Sudden / Q000209:etiology*; D004827:Epilepsy / Q000150:complications* / Q000188:drug therapy / Q000453:epidemiology; D006801:Humans; D012307:Risk Factors; D012640:Seizures / Q000150:complications* / Q000188:drug therapy
chemical_list: D000927:Anticonvulsants