A higher risk of SUDEP is found among patients with epilepsy who receive placebo in randomized controlled trials, according to researchers.
BOSTON—The global incidence of Sudden Unexpected Death in Epilepsy (SUDEP) that occurs in the double-blind phase of add-on randomized placebo-controlled trials is five times lower in patients who receive an additional AED at an efficacious dosage, and 50% higher in those receiving a placebo, according to research presented at the 63rd Annual Meeting of the American Epilepsy Society.
“This observation questions the safety of double-blind, placebo-controlled randomized trials in patients with drug-resistant epilepsy, and raises the issue of an alternative strategy for the optimal development of new AEDs,” Philippe Ryvlin, MD, and coauthors stated.
Dr. Ryvlin, Professor of Neurology at the University Hospital of Lyon, France, and colleagues searched two electronic databases for all randomized placebo-controlled trials that used any AED in the add-on treatment of patients with drug-resistant epilepsy.
Patients were separated into three groups: those who were randomized to an AED at an efficacious dosage, those randomized to an AED at a nonefficacious dosage versus placebo, and those randomized to placebo. The incidence of SUDEP was calculated for each group, per 1,000 patient-years and according to the duration of the treatment phase of each trial.
SUDEP incidence was compared across groups using three scenarios: an AED at efficacious dosage versus placebo, an AED at both efficacious and nonefficacious dosages versus placebo, and an AED at efficacious dosage versus placebo and an AED at nonefficacious dosage.
Both the primary and sensitivity analyses revealed that the risk of SUDEP is significantly greater in patients who received placebo, compared with those who received AEDs.
In the primary analysis, the scenario that compared an efficacious dose of an AED with placebo, the odds ratio (OR) for SUDEP was 0.12. In the scenario that compared both efficacious and nonefficacious doses with placebo, the OR for SUDEP was 0.21. In the scenario that compared efficacious doses with placebo and nonefficacious doses of AEDs, the OR for SUDEP was 0.12.
—Laura Sassano