Suicidality at Epilepsy Diagnosis Predicts Future Drug Resistance Risk
Key Clinical Summary
- Suicidality at the time of focal epilepsy diagnosis was linked to a more than twofold increased risk of antiseizure medication (ASM) treatment resistance.
- In a prospective international cohort of 347 adults, 24% developed treatment-resistant epilepsy and 38% had psychiatric disturbances at diagnosis.
- Early psychiatric screening may help identify patients at higher risk for refractory epilepsy and guide clinical management.
Psychiatric disturbances are common among patients with epilepsy and may influence disease outcomes. A prospective cohort study published in JAMA Neurology found that suicidality at the time of focal epilepsy diagnosis was linked to a more than twofold increased risk of future antiseizure medication (ASM) treatment resistance.
Study Findings
Researchers analyzed data from the Human Epilepsy Project (HEP), an international multicenter observational study, to determine whether mood disorders, anxiety disorders, or suicidality at diagnosis are associated with subsequent drug-resistant epilepsy. The study enrolled adults aged 18–60 years with newly diagnosed focal epilepsy between 2012 and 2020. Participants were recruited within 4 months of initiating ASM therapy and followed for up to 6 years.
Among 376 enrolled individuals, 347 completed psychiatric assessments at baseline using the Mini International Neuropsychiatric Interview (MINI) and the Columbia-Suicide Severity Rating Scale (C-SSRS). The cohort had a median age at seizure onset of 33 years (IQR, 23–44) and 60.2% were female. Treatment outcomes were categorized as:
- Treatment-sensitive (TS): seizure freedom during the first 2 adequate ASM trials
- Treatment-resistant (TR): ongoing seizures despite 2 adequate ASM trials
- Indeterminate: neither outcome met
Overall, 55% (191 patients) were treatment sensitive, 24% (83) developed treatment-resistant epilepsy, and 21% (73) had indeterminate outcomes. Psychiatric disturbances at diagnosis were common, occurring in 38% of participants (n = 133). Specifically, 16% had mood or anxiety disorders without suicidality and 22% reported suicidality, with or without another psychiatric disorder.
The study found that suicidality at epilepsy diagnosis was associated with more than a twofold increased risk of treatment resistance (relative risk [RR], 2.02; 95% CI, 1.32–3.09; P = .001). Patients without psychiatric disturbances had a 16.3% probability of treatment resistance, while those with suicidality alone had a 47.1% probability (RR, 2.89; 95% CI, 1.65–5.05; P < .001).
Anxiety disorder alone increased treatment resistance probability to 32.9% (RR, 2.02; 95% CI, 1.10–3.71; P = .02), though the association did not remain statistically significant after correction for multiple comparisons. Mood disorder alone did not significantly alter risk; however, mood disorder combined with suicidality increased treatment resistance probability to 39.6% (RR, 2.43; 95% CI, 1.26–4.68; P = .008).
Clinical Implications
Treatment-resistant epilepsy remains a major clinical challenge, often associated with reduced quality of life, increased morbidity, and higher mortality risk. Early identification of patients likely to develop refractory disease could influence treatment strategies, monitoring intensity, and referral decisions, including earlier consideration of specialized epilepsy care or advanced therapies.
The findings highlight a potential relationship between psychiatric symptoms at epilepsy diagnosis and subsequent treatment response. Routine psychiatric screening at diagnosis, using standardized tools such as the MINI or C-SSRS, may therefore provide valuable prognostic information.
The study also suggests that suicidality may serve as a clinical marker of more severe underlying neuropathology, though further research is needed to clarify mechanisms.
Expert Commentary
Because the study focused on adults with newly-onset epilepsy and limited medical comorbidities, the findings may not be generalizable to all types of epilepsies, noted Sarah N. Barnard, MD, MIPH, Department of Neuroscience, School of Translational Medicine, Monash University, Melbourne, Victoria, Australia, and study co-authors.
Still, the researchers concluded that the “early identification of suicidality at the time of epilepsy diagnosis may help stratify risk and guide more proactive treatment strategies to improve long-term outcomes.”
