Epilepsy patients receiving additional treatment with anti-epileptic drugs (AEDs) have an approximately seven times lower risk of dying from a sudden unexpected death according to new research published online first in The Lancet Neurology.

In comparison with the general population, sudden unexplained death is 20 times more common in people suffering from epilepsy. Researchers have found some potentially preventable risk factors for sudden unexpected death in epilepsy (SUDEP), such as large numbers of generalized tonic-clonic seizures (the most common type of generalized seizure affecting the entire brain) and taking a combined regimen of AEDs (polytherapy). Until recently, no research has examined or developed a beneficial effect at preventing SUDEP in a controlled study.

Philippe Ryvlin from the Hôpital Neurologique in Lyon, France, and his team collated data from 112 randomized trials of AED adjunctive treatment of adults with treatment-resistant (refractory) epilepsy to evaluate comparisons of definite and probable SUDEP incidences between patients receiving add-on AED therapy at effective doses and those given placebo.

During the trials a total of 33 patients died, with 18 deaths being caused by probable or definite SUDEP, and two deaths due to possible SUDEP.

Analyses revealed in general that patients treated with adjunctive AEDs at effective doses had a seven times reduced risk of dying a SUDEP compared with those given placebo with rates of definite and probable SUDEP being 0.9 per 1000 person-years in the AED group and 6.9 per 1000 person-years in the placebo group.

According to the authors, treatment-related reduction in the frequency of seizures seems the most likely explanation for significantly low rate of SUDEP in patients administered with AEDs at effective doses. Opposing research’s suggestion that polytherapy might increase the risk of SUDEP, the authors point out, stating: “Our data suggest that add-on AEDs at doses effective on seizure frequency reduce the risk of SUDEP despite increasing the drug load, at least during the average 3-month duration of randomized trials,” concluding that, “This finding provides an argument not only for active revision and optimum management of treatment in patients with uncontrolled seizures, but also for further prospective and long-term investigation of this unsettled issue.”

Dale Hesdorffer from Columbia University in New York, USA and Torbjorn Tomson from the Karolinska Institute in Stockholm, Sweden, outline three key implications of the findings in a comment:

“First, the study provides strong evidence for an effective intervention to reduce SUDEP risk. Second, the protective effective of adjunctive therapy suggests that seizure control could be extremely important for SUDEP prevention. Third, polytherapy does not increase risk of SUDEP during the time period of a randomized trial.”

Written by Petra Rattue