DAY 2 | Depression Complicates the Management of Newly Diagnosed Epilepsy

Patients with newly diagnosed epilepsy and depression are more likely to discontinue or switch first-line therapies than those without depressive symptoms, resulting in an increased risk of treatment failure, according to a study presented at the 2025 American Epilepsy Society Annual Meeting (AES 2025) in Atlanta, Georgia. 

A retrospective analysis of U.S. health insurance claims was conducted to assess the burden of depression among patients with a new diagnosis of epilepsy, as well as the effects of psychiatric comorbidities on treatment patterns and outcomes in this population. Samuel Terman, MD, assistant professor of neurology at the University of Michigan Medical School, in Ann Arbor, and co-authors identified more than 90,000 patients newly diagnosed with epilepsy whose claims for anti-seizure medications were submitted between January 1, 2016 and December 31, 2023. More than 60% of the individuals included in the analysis were Medicare beneficiaries, while the rest of the claims were submitted to Managed Medicaid (24.6%) and to commercial insurance plans (11.1%). 

Nearly one-quarter (24%) of the included patients had comorbid depression. The analysis showed that patients with epilepsy and depression tend to have a complex clinical profile and to experience a higher comorbidity burden compared with those without depression. The prevalence of chronic cardiometabolic diseases such as diabetes, heart failure, and peripheral vascular disease was higher among the patients with depression than among the rest of the participants. A significant proportion of this group had multiple psychiatric comorbidities; more than half of the patients with depression were also diagnosed with anxiety disorders and over 40% reported sleep disorders. 

The authors found that depression was also associated with a shorter duration of initial therapy and with an increased risk of treatment failure, suggesting that this population could benefit from personalized treatment approaches. The results showed that patients with depression continued the first line of therapy for epilepsy for a shorter time compared with those without depression (4.8 months vs. 5.8 months). The duration of the subsequent lines of therapy was similar between the two groups, with modest declines over time. Logistic regression analysis, adjusted for age, sex, race, ethnicity, and payer, demonstrated significantly higher odds of treatment failure among patients with depression compared to those without depression.

“This is the largest and most diverse study [looking at] real-world treatment outcomes in patients newly diagnosed with epilepsy,” Terman said during a poster presentation at AES 2025. “While the data are based mostly on Medicare claims, these findings from across the country have the highest [degree of] generalizability to other populations.”