OBJECTIVE: Comorbidities in patients with seizure disorders impose significant burdens on patients and families. The purpose of this study was to assess the effect of comorbidities on medical care use and cost among patients with partial seizure disorder who were also refractory to anti-epileptic drug (AED) monotherapy. METHODS: Retrospective data from PharMetrics claims database, which includes 57 managed care plans, were collected for adult patients treated with AEDs between January 1, 2000 and March 30, 2000. Patient data were analyzed over a 6-month baseline period prior to treatment failure (on carbamazepine, phenytoin, or valproic acid monotherapy), and over a 12-month follow-up period. The Charlson Comorbidity Index (CCI) was calculated for each patient. Econometric analysis of total cost and a logistic regression with hospitalization as the dependent variable, examined the impact of the CCI, controlling for age, gender, geographic location, observation period, and AED therapy during follow-up. RESULTS: Data from 549 patients were analyzed. Sixty-percent of patients were male; 25.3% of patients were 18-30 years old, 35.2% 31-45, and 39.5% were ³46. Headache (10.6%), migraine (4.7%), depression (6.9%) and brain tumor (4.0%) were frequently recorded, with headache (p<0.05) and migraine (p<0.01) more common among females. Hypertension and hyperlipidemia occurred most often in the oldest age category (p<0.001), being reported among 20.3% and 10.1% of patients >46 years old. During follow-up, among patients with a CCI > 1, the odds of hospitalization were nearly 3.5 times greater than for patients without recorded comorbidities (OR=3.46, p<0.05), while treatment costs for all medical care were 1.3 times greater (p<0.10). CONCLUSIONS: These analyses suggest that, for patients refractory to initial standard AED monotherapy, the presence of comorbidities substantially increase medical care use and costs for managed care plans.