OBJECTIVES: Monotherapy with antiepileptic drugs (AEDs) is the preferred initial management approach in patients with epilepsy. Differences in treatment patterns were assessed across monotherapy and combination therapy users. METHODS: Texas Medicaid medical and prescription claims from January 1, 2007 - October 31, 2010 were extracted for adults (18-63 years) diagnosed with epilepsy. The index date was the first date of AED use with no previous use in the 6-month pre-index period. Patients were followed for 12 months. Combination therapy was defined as the use of ≥2 AEDs with an overlap of at least 14 days following index date. Treatment patterns consisting of additions, switches, and discontinuations in the 1-year follow up period were assessed for patients on mono vs. combination therapy.  Logistic regression was used to evaluate the association of mono vs. combination therapy and types of treatment patterns while controlling for demographics, chronic disease score (CDS), mental comorbidities, and type of epilepsy. SAS 9.3 was used for statistical analyses. RESULTS: Patients with epilepsy (n=4,163) had a mean age of 37.8±13.3 years, were primarily female (57.8%), White (41.5%), on monotherapy (87.6%), with a mean CDS of 1.2±3.0. Of the patients on monotherapy (n=3,647) 4.3% added, 14.2% switched, and 46.7% discontinued the index AED. Of the patients on combination therapy (n=516), 5.6% added, 7.9% switched, and 38.6% discontinued at least one of the index AEDs. Logistic regression showed that the likelihood of change in treatment patterns was significantly higher in the monotherapy group (odds ratio=1.7; confidence interval=1.401-2.039; p<0.0001) as compared to the combination therapy group, while controlling for covariates. CONCLUSIONS: Patients on monotherapy were more likely to change treatment patterns as compared to those on combination therapy in Texas Medicaid. Future research assessing the benefits of combination therapy over monotherapy is needed.