VALHALLA, NY – April 7, 2026 – Adults newly diagnosed with focal epilepsy who report suicidality may be far more likely to develop treatment-resistant seizures, according to a new study published in JAMA Neurology. Findings from the international Human Epilepsy Project (HEP) suggest that psychiatric symptoms present early in a patient’s diagnosis may be an important marker of disease severity, helping clinicians identify patients at higher risk for poor treatment response and connect them to timely, specialized care.
Psychiatric conditions are common in people with epilepsy and can be associated with lower quality of life, increased premature mortality, and reduced response to antiseizure medications. However, whether psychiatric symptoms present at the time of diagnosis can help predict long-term treatment outcomes has been less clear.
“This study reinforces why comprehensive epilepsy care must include mental health assessment from day one,” said Manisha Holmes, MD, Epilepsy Section Chief at Westchester Medical Center. “By screening for suicidality at diagnosis, we can identify patients who may be at higher risk for treatment-resistant seizures, intensify follow-up when appropriate, and connect people to support that can improve both safety and long-term outcomes.”
Key Findings
Researchers analyzed data from 376 adults (ages 18 to 60) with newly diagnosed focal epilepsy enrolled in the Human Epilepsy Project between 2012 and 2020. Participants enrolled within four months of starting antiseizure medication therapy. Psychiatric symptoms at enrollment were assessed using standardized tools, including the Mini International Neuropsychiatric Interview (MINI) and the Columbia-Suicide Severity Rating Scale (C-SSRS).
- Patients who reported current or past suicidality at diagnosis had a higher risk of future treatment resistance and were about twice as likely to develop resistance to antiseizure medications (relative risk [RR], 2.02; 95% confidence interval [CI], 1.32-3.09; P = .001).
- The probability of developing treatment-resistant epilepsy was 16.3% among patients without any psychiatric disturbance (95% CI, 11.3-21.3), compared with 47.1% among those who reported suicidality at diagnosis (RR, 2.89; 95%CI, 1.65-5.05; P < .001).
- Depression and anxiety alone were not significantly associated with treatment resistance. However, mood disorder combined with suicidality was associated with a higher likelihood of a poor treatment response (39.6%; RR, 2.43; 95% CI, 1.26-4.68; P = .008).
A Call for Early Screening
The researchers emphasize that routine screening for suicidality at the time of epilepsy diagnosis could play a critical role in patient care. Identifying at-risk individuals early may help inform prognosis, guide clinical decision-making and interventions, and support individualized treatment strategies.
About the Study
The Human Epilepsy Project (HEP) is a prospective, observational, international, and multicenter cohort study with follow-up of 376 adults aged 18 to 60 with newly diagnosed focal epilepsy for up to six years. Researchers assessed psychiatric conditions and suicidality at diagnosis and tracked how patients responded to treatment over time.
The study was authored by Sarah N. Barnard, MD, MIPH; Jacqueline A. French, MD; Zhibin Chen, PhD; and Manisha Holmes, MD, et al, on behalf of the HEP1 study investigators.
The researchers underscore the need for further studies to better understand the connection between mental health and epilepsy, and to improve outcomes for patients living with this complex condition.