Reducing the number of generalized seizures may help prevent SUDEP, while use of one particular AED may increase the risk, according to researchers.
SAN ANTONIO—An increased frequency of generalized tonic-clonic seizures (GTCS) and antiepileptic drug (AED) polytherapy are significant risk factors for sudden unexpected death in epilepsy (SUDEP), reported Dale C. Hesdorffer, PhD, and colleagues.
Other risk factors for SUDEP include a long duration of epilepsy, young age at onset, gender, symptomatic cause, and use of lamotrigine therapy, said Dr. Hesdorffer at the 64th Annual Meeting of the American Epilepsy Society.
“The emerging profile from our pooled analysis indicates that people with early-onset refractory symptomatic epilepsy who have frequent GTCS and take more than one AED are at highest risk,” said Dr. Hesdorffer, Associate Professor of Neurology, Gertrude H. Sergievsky Center, Columbia University in New York City. “The results suggest that reducing the number of these generalized seizures is a priority of more importance than reducing the number of AEDs.”
Pooled Analysis Strengthens Risk Factor Assessment
Previous case-control studies using living patients with epilepsy as controls have aimed at identifying factors that distinguish those at risk of SUDEP, but a lack of precision in the risk estimates was attributed, in part, to the small number of cases in each study. To counterbalance those study limitations, the Epidemiology Task Force of the International League Against Epilepsy pooled data from four published studies of SUDEP from the United States, Sweden, Scotland, and England.
The investigators defined patients with SUDEP as having: 1) a history of epilepsy (one or more seizures during a five-year period); 2) death occurring suddenly; 3) death unexpected with no life-threatening illness; and 4) death remaining unexplained after all investigative efforts, including autopsy. Definite SUDEP required meeting all four criteria.
“Results persisted when epilepsy onset was younger than 16 and when it was 16 or older,” stated Dr. Hesdorffer. “In univariate analysis, lamotrigine therapy was associated with a significantly increased risk for SUDEP among individuals with idiopathic generalized epilepsy.”
The researchers noted that the role of AEDs and other forms of epilepsy treatment should be analyzed further in future studies. Another challenge for future research is to focus on patients with refractory epilepsy to clarify what features may distinguish the patients in this high-risk population who die with SUDEP from those who survive.
SUDEP, Gender, and AEDs
In a separate study, Dag Aurlien, MD, and colleagues found that the incidence of SUDEP in patients treated with lamotrigine therapy was significantly increased, compared with use of other AEDs, with a higher incidence in women.
The researchers’ analysis focused on 26 cases (15 females) of SUDEP. All but one patient were taking an AED, either as monotherapy or as polytherapy. Among the 26 cases, 16 were definite, three were probable, and seven were possible. The incidence of SUDEP was 1.0 per 1,000 patient-years when all 26 cases were included and 0.7 per 1,000 patient-years for definite and probable SUDEP. Two of 10 patients using lamotrigine were classified as possible SUDEP, and both were on polytherapy. Eight of the 19 cases (42%) classified as definite or probable SUDEP were taking lamotrigine.
The incidence of SUDEP for patients treated with lamotrigine (all cases included) was 4.9 per 1,000 patient-years, compared with 0.7 per 1,000 patient-years for patients who were not treated with lamotrigine. The incidence of definite and probable SUDEP for patients treated with lamotrigine was 3.9 per 1,000 patient-years and 0.46 per 1,000 patient-years for those who were not treated with lamotrigine.
Among the 26 cases, seven were treated with carbamazepine (four in monotherapy) and eight with valproate (four in monotherapy). The SUDEP incidence for carbamazepine and valproate was not significantly different from the incidence among those not treated with these AEDs. In addition, three patients were treated with phenytoin, three with vigabatrin, three with oxcarbazepine, two with topiramate, one with phenobarbital, and one patient was untreated.
“Our findings may suggest a gender difference with a higher incidence of SUDEP among women treated with lamotrigine,” said Dr. Aurlien, of the Stavanger University Hospital in Norway, “although the total incidence of SUDEP in our study was similar to that of previous population-based studies.”