Objective: To evaluate the healthcare and societal economic burden of adjunctively-treated patients with uncontrolled epilepsy. 

Methods: A retrospective claims database (representative of the commercially insured US population) was used to analyze direct and indirect costs (Jan-2006 to Dec-2011) for patients with epilepsy. Patients had ≥1 diagnosis code for epilepsy (ICD-9 345.xx), ≥18 years of age, and had received ≥1 add-on Anti Epileptic Drug (AED) within 60 days of first-line treatment. Patients were grouped into: Well-controlled (no change in AED and no epilepsy-related Emergency Room (ER) or inpatient visits), Uncontrolled (≥2 AED changes in ≥30 days and ≥1 Epilepsy-Related ER or inpatient visits), and Intermediate-controlled (not grouped as Uncontrolled or Well-controlled). The groups were matched based on propensity scoring in a 1:1:1 ratio including age, sex, and Charlson comorbidities index score. A mixed-effects model was used to calculate the adjusted cost differences. 

Results: From 141,173 patients, 6,785 triads were included in the analysis. Mean age was 48±16.6 years (62% female). Uncontrolled patients had significantly higher direct costs: Uncontrolled vs. Well-controlled: $32,077; Uncontrolled vs. Intermediate-controlled: $14,855. Indirect costs were: Uncontrolled vs. Well-controlled: $5,016; Uncontrolled vs. Intermediate-controlled: $2,750. Differences were due to hospitalization costs (Uncontrolled/ Well-controlled: $15,297; Uncontrolled/Intermediated-controlled: $9,123), outpatient visits (Uncontrolled/Well-controlled: $9,248; Uncontrolled/Intermediated-controlled: $4,534), AED costs (Uncontrolled/Well-controlled: $4,546; Uncontrolled/ Intermediate-controlled: $3,079), sick leave costs (Uncontrolled/ Well -controlled:  $4,849; Uncontrolled/Intermediate-controlled: $2,577), and total work loss (Uncontrolled/ Well-controlled: Uncontrolled/Intermediate-controlled : $2,750) $5,016;  (all p<0.01).Adjusted costs were significantly higher for Intermediate-control vs. Well-controlled patients for all cost items (all p<0.01), with the exception of non-AED costs and disability, which were not significantly different. 

Conclusions: In this study, direct and indirect costs were highest for uncontrolled, and lowest for well-controlled epilepsy. These findings suggest the importance of improvements in control of seizure activity (either from uncontrolled to intermediate-controlled, or  from intermediate-controlled to well-controlled), both from a societal cost and public health perspective.