title: Sudden unexplained death in epilepsy: observations from a large clinical development program.
abstract: OBJECTIVE
  The present study was conducted to determine the rate of sudden unexplained death in epilepsy (SUDEP) in a well-defined cohort of patients included in the lamotrigine (LTG) clinical development database.
  
  
  METHODS
  A panel of scientists experienced in the area of SUDEP was assembled and provided with case summaries on all deaths (n = 45) reported during the initial clinical development of LTG. The panel developed a set of criteria for classifying cases as SUDEP (definite or highly probable), possible SUDEP, or non-SUDEP. This classification algorithm was then applied to the LTG cases, and SUDEP rates were calculated using patient-years of exposure as the denominator.
  
  
  RESULTS
  At the time of the study, 4,700 patients (5,747 patient-years of exposure) were included in the worldwide LTG clinical trials database. In this cohort, 45 deaths were reported. Eighteen were judged by the panel to be SUDEP, 6 were defined as possible SUDEP, 20 were judged to be due to other causes (non-SUDEP), and 1 lacked sufficient data from which to make a classification. The overall SUDEP rate (definite/ highly probable SUDEP and possible SUDEP combined) was calculated to be 3.5 in 1,000 patient-years of exposure to LTG.
  
  
  CONCLUSIONS
  The rate of SUDEP in this cohort of patients was comparable to the rate that would be expected in young adults with severe epilepsy (the subgroup of patients believed to be at highest risk of SUDEP). The data suggest that the rate of SUDEP in the LTG clinical development program is a function of the clinical trial population and is unrelated to drug treatment.
authors.affiliation: Chicago Institute of Neurosurgery and Neuroresearch, Illinois, USA.
authors.forename: J E
authors.initials: JE
authors.lastname: Leestma
authors.forename: J F
authors.initials: JF
authors.lastname: Annegers
authors.forename: M J
authors.initials: MJ
authors.lastname: Brodie
authors.forename: S
authors.initials: S
authors.lastname: Brown
authors.forename: P
authors.initials: P
authors.lastname: Schraeder
authors.forename: D
authors.initials: D
authors.lastname: Siscovick
authors.forename: B B
authors.initials: BB
authors.lastname: Wannamaker
authors.forename: P S
authors.initials: PS
authors.lastname: Tennis
authors.forename: M A
authors.initials: MA
authors.lastname: Cierpial
authors.forename: N L
authors.initials: NL
authors.lastname: Earl
mesh_terms: D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000627:therapeutic use; D002423:Cause of Death; D002648:Child; D002986:Clinical Trials as Topic; D015331:Cohort Studies; D003645:Death, Sudden / Q000453:epidemiology*; D004332:Drowning / Q000453:epidemiology; D004827:Epilepsy / Q000188:drug therapy / Q000453:epidemiology / Q000401:mortality*; D005260:Female; D006801:Humans; D000077213:Lamotrigine; D008297:Male; D008875:Middle Aged; D010919:Placebos; D014227:Triazines / Q000627:therapeutic use
chemical_list: D000927:Anticonvulsants; D010919:Placebos; D014227:Triazines; D000077213:Lamotrigine