Suicidality Is Key Predictor of Treatment-Resistant Focal Epilepsy
Study in JAMA Neurology Shows Suicidality More than Doubles the Risk of Treatment Resistance in Newly Diagnosed Focal Epilepsy Patients
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Affecting 65 million people worldwide, epilepsy has long been associated with co-occurring mental health conditions. Now, a new study published in JAMA Neurology, by a team of researchers, including Manisha Holmes, M.D., associate professor of neurology, has found that patients with newly diagnosed focal epilepsy who experience suicidality—the spectrum of suicidal thoughts, plans, and behaviors—are more than twice as likely to develop treatment-resistant epilepsy than those without mental health conditions.
“This study reinforces a simple but powerful point: brain health and mental health are inseparable,” says Dr. Holmes. “Clinically, we know that psychiatric comorbidities and epilepsy outcomes are closely linked, but most prior work focused on depression and anxiety. What was striking here was how clearly suicidality emerged as the strongest signal. That finding suggests we may have been missing an important risk marker by not routinely and explicitly assessing suicidality at the time of diagnosis.”
The study drew on data from individuals with newly diagnosed focal epilepsy who were enrolled in the much broader Human Epilepsy Project, an international, multicenter, prospective, observational initiative spanning 34 tertiary epilepsy centers in the United States, Australia, and Europe. Using a well-characterized cohort of 347 individuals, the researchers found that nearly 40 percent of participants had psychiatric symptoms when their focal epilepsy was first identified. Notably, individuals who reported current or past suicidality were far more likely to fail their first two antiseizure medications—47 percent compared with 16 percent among those without psychiatric conditions.
Importantly, this association remained even after accounting for co-occurring depression or anxiety, notes Dr. Holmes, suggesting that suicidality itself carries unique prognostic information, beyond other psychiatric diagnoses.
“Historically, psychiatric symptoms identified around the time of epilepsy diagnosis have often been viewed as reactive, developing in response to the stress of living with a chronic neurological condition,” explains Dr. Holmes. “This study challenges that assumption. By evaluating psychiatric status right at diagnosis, before long treatment histories accumulate, we were able to examine the more fundamental question of whether early psychiatric symptoms reflect something about the underlying biology of epilepsy.”
The findings underscore the importance of routinely screening for suicidality at the time of an epilepsy diagnosis, not only to ensure patient safety, which remains paramount, but also because this information may help clinicians identify individuals at greater risk for medication resistance.
“For clinicians, asking about suicidality is not only a psychiatric concern—it can also provide important insight into the patient’s neurological disease and potential treatment course,” says Dr. Holmes. “For patients and families, it highlights the importance of openly discussing mental health symptoms, which can help clinicians provide safer and more personalized care.”
