New Insights Into Depression and Epilepsy

Individuals diagnosed with epilepsy who also have depression face significantly higher rates of treatment failure and shorter durations of initial treatment compared to those without depression, according to a retrospective claims analysis presented at the 2025 American Epilepsy Society (AES) Annual Meeting. The findings underscore the need for individualized treatment approaches for individuals with epilepsy and comorbid depression.

Researchers used 100% Medicare Fee-for-Service claims and the Inovalon MORE2 closed claims database (Bowie, MD) to identify participants in the study. In all, data was analyzed for 90,738 individuals who were newly diagnosed with incident epilepsy between 2017 and 2019 defined as ≥2 outpatient (OP) or ≥1 inpatient (IP) claims per ICD-10 codes. 

Participants were then stratified into 2 cohorts: 

Depression (21,388, 24%), defined as ≥2 OP or ≥1 IP claims with ICD-10 codes

and

No depression (69,350, 76%) cohorts. 

Lines of therapy (LOTs), including the initial line of therapy (LOT1), and treatment failure were tracked, with up to 4 LOTs captured per patient.

Key findings included:

• Participants in the depression cohort remained on LOT1 for less time than those in the no depression cohort (median length: 145 days vs 173 days). 
• Regression analysis, adjusted for age, sex, race/ethnicity, and payer, found that the depression cohort had significantly higher odds of treatment failure than others (odds ratio [OR] 1.41; 95% CI: 1.34-1.48).
• The depression cohort had a higher proportion of female participants (62% vs 53%). 
• The depression cohort had a higher mean Deyo Charlson Comorbidity Index (CCI) score (3.5 vs 2.5), with 41% having a score of ≥4 vs 27% in the no depression cohort.
• Psychiatric comorbidities were markedly elevated in the depression group: anxiety (65% vs 24%), sleep disorders (42% vs 21%), psychosis (20% vs 8%), and bipolar disorder (18% vs 8%).
• Chronic cardiometabolic and systemic diseases were more prevalent in the depression cohort, including chronic obstructive pulmonary disease (COPD), diabetes, renal disease, heart failure, and peripheral vascular disease (PVD).

​Source: Terman S, Ong A, Davis T, et al. Impact of depression on treatment patterns and outcomes in patients with newly diagnosed epilepsy: a retrospective claims analysis. Presented at: American Epilepsy Society Annual Meeting; December 5–9, 2025; Atlanta, GA.