SUDEP: What Are the Risk Factors? Do Seizures or Antiepileptic Drugs Contribute to an Increased Risk?

Commentary Although sudden unexpected death in epilepsy (SUDEP) is one of the most frequent causes of death among patients with epilepsy (1), risk factors identifying those most at risk have not been clarified. Currently, epilepsy and seizure severity factors including generalized tonic seizures (GTCS) are most commonly associated with SUDEP (1–4). In addition, studies suggest that antiepileptic drug PURPOSE: 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. KEY FINDINGS: 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 mono-therapy, polytherapy, or total number. GTCS frequency remained strongly associated with an increased risk for SUDEP. SIGNIFICANCE: Our findings—that none of the AEDs considered were associated with increased SUDEP risk as mono-therapy 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. PURPOSE: Most people with epilepsy who die suddenly and whose death is attributed to sudden unexpected death in epilepsy (SUDEP) are found in or by the bed for unknown reasons. We assessed whether those with sleep-related SUDEP were more likely to have nocturnal seizures, and whether seizure patterns (diurnal vs. nocturnal) differed from people dying suddenly and living controls with epilepsy. METHODS: Seizure patterns in a cohort of 154 people with epilepsy who died suddenly and after autopsy conformed to the definition of SUDEP and 616 controls living with …