Effectiveness of antiepileptic drug combination therapy for partial-onset seizures based on mechanisms of action

Jay M. Margolis, Bong L. Chu, Zhixiao J. Wang, Ronda Copher, Jose E. Cavazos

Research output: Contribution to journalArticlepeer-review

102 Scopus citations


IMPORTANCE: To our knowledge, the current study is the first to describe antiepileptic drug (AED) combination therapy patterns according to their mechanism of action (MOA) in a real-world setting and to evaluate the differences in outcomes comparing different-MOA combination therapy with same-MOA combination therapy for patients with partial-onset seizure. OBJECTIVE: To compare treatment persistence and health care use with AED combinations categorized by MOA in patients with partial-onset seizures. DESIGN, SETTING, AND PARTICIPANTS: Using the Truven Health Market Scan Commercial Claims Database containing 96 million covered lives from July 1, 2004, through March 31, 2011, adults with concomitant use of 2 different AEDs and a recent partial-onset seizure diagnosis were selected. Antiepileptic drugs were categorized by MOA: sodium channel blockers (SC), gamma-aminobutyric acid analogs (G), synaptic vesicle protein 2A binding (SV2), and multiple mechanisms (M). Patients were assigned a combination category based on their concomitant AED use. MAIN OUTCOMES AND MEASURES: Treatment persistencewas measured from the start of AED combination therapy until the end of the combination. Health care resource use was measured during the combination treatment duration. Multivariate analyses evaluated AED discontinuation risk and health care use according to MOA combinations. RESULTS: Distribution of 8615 selected patients by combination was 3.3% for G+G, 7.5% for G+SV2, 8.6% for G+M, 13.9% for SC+SC, 19.0% for G+SC, 21.5% for SC+M, and 26.3% for SC+SV2. The same-MOA (G+G and SC+SC) combinations had the shortest persistence (mean [SD], 344 [345] days and 513 [530] days, respectively) and greater hazard of discontinuation compared with different-MOA combinations. Patients with different-MOA G combinations had a significantly lower risk for inpatient admission (odds ratio, 0.716; 95% CI, 0.539-0.952; P = .02) compared with G+G combinations. Patients with different-MOA SC combinations had significantly lower risks for emergency department visits (odds ratio, 0.853; 95%CI, 0.742-0.980; P = .03) compared with SC+SC combinations. CONCLUSIONS AND RELEVANCE: The findings suggest that AED combinations with different MOAs have greater effectiveness as measured by treatment persistence and lower risks for hospitalization and emergency department visits. Further research is needed to more fully understand the role of the MOA in achieving optimal outcomes.

Original languageEnglish (US)
Pages (from-to)985-993
Number of pages9
JournalJAMA Neurology
Issue number8
StatePublished - Aug 2014

ASJC Scopus subject areas

  • Clinical Neurology


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