Little Evidence to Support Treatments for Prevention of Sudden Unexpected Death in Epilepsy

By Will Boggs MD

April 17, 2020

NEW YORK (Reuters Health) - More research is needed to identify effective interventions aimed at preventing sudden unexpected death in patients with epilepsy (SUDEP), according to an updated Cochrane review.

SUDEP occurs with an incidence of 1 to 2 per 1,000 patient-years and is the most common epilepsy-related cause of death. Predictors of SUDEP risk include the presence and frequency of generalized tonic-clonic seizures (GTCS), male sex, early age of seizure onset, duration of epilepsy, and polytherapy.

Whether any of the current preventive strategies for SUDEP is effective remains unclear.

To investigate, Dr. Melissa J. Maguire of Leeds General Infirmary, in the UK, and colleagues searched for studies of early versus delayed presurgical evaluation for lesional epilepsy; educational programs; seizure-monitoring devices; safety pillows; nocturnal supervision; selective serotonin reuptake inhibitors (SSRIs); opiate antagonists; and adenosine antagonists.

Out of 33 full-text articles they screened, the authors excluded 29, of which eight did not assess interventions to prevent SUDEP, eight were actually review articles, five measured sensitivity of devices to detect GTCS but did not directly measure SUDEP, six assessed risk factors for SUDEP but not interventions to prevent it, and two lacked a control group.

All four included studies showed serious to critical risk of bias, the researchers report in the Cochrane Database of Systematic Reviews.

One six-month prospective cohort study found no significant benefit in terms of drug compliance, quality of life, anxiety, or depression of providing SUDEP information to patients. There were no deaths in either group, making it impossible to determine a protective effect.

Two case-control studies reported significant protective effects of nocturnal supervision against SUDEP, with one study reporting 66% lower odds and the other study reporting 92% lower odds of SUDEP with nocturnal supervision.

A third case-control study of patients at a residential care center who were already receiving physical checks more than 15 minutes apart throughout the night reported no protective effect for additional nocturnal supervision (less than 15 minutes apart), although residential centers with the lowest level of supervision had the highest incidence of SUDEP.

"We found limited, very low-certainty evidence that supervision at night reduces the incidence of SUDEP," the authors conclude. "Further research is required to identify the effectiveness of other current interventions in preventing SUDEP in people with epilepsy."

Dr. Orrin Devinsky of New York University School of Medicine's Comprehensive Epilepsy Center, who studies SUDEP, told Reuters Health by email, "Nocturnal monitoring is worth pursuing as long as someone is nearby who can attend to the person with epilepsy. If I have a seizure at 5 am in bed alone and my brother is notified 20 miles away, he can't do much to save me. It would need to be someone in my home or very close who comes to provide basic aid (rolling me over if face down, gently stimulating by calling my name, etc.)."

"The big message is to prevent seizures," said Dr. Devinsky, who was not involved in the review. "Everyone with epilepsy or even a single seizure is at risk. Patients and neurologists and other doctors/nurses caring for people with epilepsy need to understand and know about SUDEP - too often a person dies and the family had no idea that SUDEP existed."

"We need more rigorous scientific study," Dr. Devinsky said. "The problem is that SUDEP is a rare event and large studies will be needed."

The North American SUDEP Registry provides data for researchers aiming to advance SUDEP understanding and prevention. More information is available at

Dr. Maguire did not respond to a request for comments.

SOURCE: Cochrane Database of Systematic Reviews, online April 2, 2020.