Mortality in epilepsy and the influence of comorbid conditions and antiepileptic drugs

Abstract

Purpose: Based on a clinical observation, this study was initiated to examine whether treatment with lamotrigine (LTG) is associated with an increased risk of sudden unexpected death in epilepsy (SUDEP) in sub-groups of epilepsy patients, and to explore the underlying causes of the increased mortality rate in the epilepsy population. Materials and methods: A nested case-control study of SUDEP in Rogaland county, Norway was conducted by review of post mortem reports, data from the Norwegian Cause of Death Registry, and hospital records. We also examined twenty-six newly diagnosed epilepsy patients by signal-averaged and standard electrocardiography. Fifteen patients were treated with LTG and ten with carbamazepine (CBZ). Furthermore the causes of death (COD) of deceased epilepsy patients at Stavanger University Hospital were compared with the COD in the general population. Results: The incidence of SUDEP was significantly elevated in females on LTG, and a significantly higher proportion of female SUDEP victims were on LTG compared with controls. No significant electrocardiographic abnormalities were detected in the 25 patients that completed the study. A significantly lower proportion of deceased epilepsy patients had died from cardiac disease compared with the general population. In a significant proportion of cases, the onset of the disorder leading to death had preceded the onset of epilepsy. Conclusions: Treatment with LTG in females was significantly associated with SUDEP. However, it remains uncertain whether a causal relationship is present. We found no evidence of cardiac abnormalities caused by LTG or CBZ. Comorbid and underlying disorders were the main determinants of mortality in the epilepsy population.