COHORT STUDY OF INCIDENCE OF SUDDEN UNEXPLAINED DEATH IN PERSONS WITHSEIZURE DISORDER TREATED WITH ANTIEPILEPTIC DRUGS IN SASKATCHEWAN, CANADA

To measure the incidence of sudden unexplained death in treated person s with epilepsy (SUDEP) and to identify risk factors for SUDEP, a coho rt of 6,044 persons aged 1549 years with more than four prescriptions for antiepileptic drugs (AEDs) was identified from the Saskatchewan He alth prescription drug file. To exclude subjects whose sudden deaths ( SUDs) might be misattributed to another chronic underlying disease, su bjects with hospitalizations for cancer or heart problems were exclude d. To exclude subjects without epilepsy, subjects with >2-year AED tre atment followed by AED-free time and subjects receiving <1 U/day were excluded. The final cohort consisted of 3,688 subjects. Follow-up was started at the first AED prescription listed in the prescription drug file and ended at the earliest of the following: age 50 years, death, or last registration in the Saskatchewan Health. For 153 of 163 deaths occurring in the cohort, copies of anonymized death certificates were obtained and copies of anonymized autopsy reports of potential SUDEP cases were examined. There were 18 definite/probable SUDs and 21 possi ble SUDEPs, yielding a minimum incidence of 0.54 SUDEP per 1,000 perso n-years and a maximum of 1.35 SUDEP per 1,000 person-years. SUDEP inci dence increased with male sex, number of AEDs ever prescribed, and pre scription of psychotropic drugs and was highest in males with a histor y of treatment with three or more AEDs and four or more psychotropic d rug prescriptions. Poisson regression showed a 1.7-fold increase in ri sk of SUDEP for each increment in maximum number of AEDs administered, a likely surrogate for severity and persistence of seizures.