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BOSTON -- Generalized tonic-clonic seizures are a risk factor for sudden unexplained death in epilepsy (SUDEP), and clinicians should emphasize control of these events to reduce mortality risk, according to a new guideline.

Epilepsy patients with three or more generalized tonic-clonic seizures per year were 15 times more likely to die suddenly than those with no tonic-clonic seizures, according to the American Academy of Neurology and American Epilepsy Society SUDEP guideline, presented during a press briefing at the AAN meeting here.

"Physicians should tell their patients that controlling seizures, especially generalized tonic-clonic seizures, may reduce the risk of SUDEP," Cynthia Harden, MD, of Mount Sinai Health System in New York and an author of the guideline, said during the briefing. "Educating physicians and people with epilepsy about SUDEP is an important first step. This guideline makes that conversation much easier, with information that might motivate people to take their medications on time, never skip their medications, and to learn and manage their seizure triggers so they can work toward reducing seizures and SUDEP risk."

Harden and colleagues conducted a systematic review of the literature on SUDEP and found that the condition is rare in children, affecting just one in 4,500 kids each year.

Its incidence is higher in adults, but still uncommon at 1 in 1,000 each year, they reported.

They reviewed several risk factors for SUDEP, but the only one that was significant was having generalized tonic-clonic seizures, they reported. The rate translated to up to 18 deaths per 1,000 patients per year in those with frequent generalized tonic-clonic seizures.

There wasn't enough evidence that any other risk factors were associated with SUDEP risk, including nocturnal seizures, any specific anti-epileptic drug, lamotrigine in women, never having been treated with an anti-epileptic drug, the number of anti-epileptic drugs used overall, heart rate variability, extratemporal epilepsy, intellectual disability, male gender, or anxiolytic drug use.

Many other risk factors had low or conflicting evidence, including psychotropic drug use, mental health disorders, duration of epilepsy, and age at epilepsy onset, the researchers added.

"People need to understand that the risk of generalized tonic-clonic seizures isn't just associated with an ability to maintain a driver's license, or work, or other outcomes like that. It's actually related to the risk of death, so it's important to reduce the frequency of tonic-clonic seizures to reduce the risk of death," said Elizabeth Donner, MD, of the Hospital for Sick Children in Toronto, a co-author of the paper.

Harden noted that using the AAN guideline methodology enabled the team to "provide nuance regarding risk factors. Even though this information is available, many neurologists don't have time to synthesize which are truly important for their patients to reduce the risk of SUDEP. We found multiple risk factors that have low evidence and didn't reach our criteria to make a recommendation."

The guideline also recommends managing epilepsy therapies to reduce seizure occurrences and the risk of SUDEP while incorporating patient preferences and weighting the risks and benefits.

Although discussions about risk of death can be challenging, Harden said neurologists often "couch it as the most severe risk of epilepsy."

"When people ask me if having tonic-clonic seizures are dangerous, my answer is truthful -- I say yes, you can die of a convulsion, so that's why we need to stop these seizures," she said.

Donner said it's not difficult to discuss the risk of SUDEP with parents of pediatric epilepsy patients because most are already thinking about it: "When parents have witnessed a convulsive seizure, they're terrified. Most say it ran through their head: Is my child going to die?"