Early Drug Resistance in Focal Epilepsy Linked to Seizure Frequency and Psychiatric History: JAMA
Australia: A new study published in JAMA Neurology highlights that most people with newly diagnosed focal epilepsy take more than a year and often require multiple antiseizure medications (ASMs) to achieve seizure freedom. The research, led by Sarah N. Barnard and colleagues from the School of Translational Medicine at Monash University, further indicates that patients with frequent pretreatment seizures and psychiatric comorbidities are at greater risk of developing drug resistance.
"Patients with newly diagnosed focal epilepsy needed extended treatment—often exceeding a year and involving more than one ASM—to attain seizure freedom, while baseline seizure frequency and mental health issues were strong indicators of treatment resistance," the authors wrote.
The findings are from the Human Epilepsy Project, an international, prospective cohort study that followed participants across 34 epilepsy centers in the US, Australia, and Europe for up to six years. The study aimed to quantify treatment response and identify predictors of resistance among individuals with newly diagnosed focal epilepsy. Participants aged 12 to 60 years were enrolled within four months of initiating ASM therapy and closely monitored to assess outcomes using standardized definitions from the International League Against Epilepsy.
The analysis of 448 participants yielded several significant findings:
- 59.6% of participants eventually became seizure-free, with 83.5% of these maintaining remission without relapse.
- Early control was uncommon; during the first year of therapy, 63% of patients continued to experience seizures or worsening symptoms.
- Most patients required more than one ASM trial to achieve stability, and the median time to seizure freedom was 12.1 months.
- For those who never relapsed, this milestone was reached much sooner—around 2.2 months—compared to 7.4 months for those who experienced recurrence.
- More than half of the cohort (54.7%) were classified as treatment-sensitive, achieving seizure control with two or fewer adequate ASM trials, and nearly 90% of these responded to monotherapy.
- About half of the treatment-sensitive group, representing 27% of the total study population, became seizure-free on their first ASM.
- Treatment resistance was seen in 22.8% of participants, while 22.5% had outcomes that did not fit either category.
- The study identified important predictors of resistance. Patients who experienced frequent seizures before treatment were significantly more likely to fail therapy compared to those with infrequent episodes.
- Individuals with a history of psychiatric disorders had an approximately 1.8-fold higher risk of developing treatment resistance than those without such conditions.
According to the authors, recognizing these risk factors early can help clinicians tailor treatment strategies and reduce the time to seizure control. The findings highlight the importance of individualized care, taking into account seizure frequency and mental health history when managing newly diagnosed focal epilepsy.
Reference:
Barnard SN, Chen Z, Holmes M, et al. Treatment Response to Antiseizure Medications in People With Newly Diagnosed Focal Epilepsy. JAMA Neurol. Published online August 25, 2025. doi:10.1001/jamaneurol.2025.2949
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