Rational Regimens: How to Combine Drugs in Treating Epilepsy

Andrew N. Wilner, MD; Jose E. Cavazos, MD, PhD


June 03, 2013

Editor's Note: While onsite at the American Academy of Neurology's 2013 Annual Meeting, held in San Diego, California, Andrew N. Wilner, MD, spoke with Jose E. Cavazos, MD, PhD, Professor of Neurology and Assistant Dean for the MD/PhD Program at the University of Texas Health Sciences Center in San Antonio, about choosing a combination treatment regimen in patients with partial-onset seizures.

Rational Antiepileptic Polytherapy

Dr. Wilner: Dr. Cavazos, you are presenting an abstract titled, "Effectiveness and Healthcare Utilization With Newly Initiated Antiepileptic Drug Combination Therapy for Partial Onset Seizures According to Mechanisms of Action."[1] I have been hearing about "rational polytherapy"; in other words, mixing antiepileptic drugs that have different mechanisms of action, as opposed to using a combination of drugs with more or less the same mechanisms of action, as the approach of choice. However, data have been lacking. Today, you provided data on several thousand patients. Can you tell me what you found?

Dr. Cavazos: We started with the records of 96 million people. Using a very strict definition of partial-onset epilepsy, we identified 8615 patients in whom first monotherapy had failed and who were newly initiating combination therapy, before pharmacoresistance is established. We categorized the medications by primary mechanisms of actions, including sodium-channel blockers, modulators of gamma-aminobutyric acid (GABA), medications that use synaptic vesicle protein 2-A (SV2) (specifically levetiracetam), and medications with broad mechanisms of action.

Dr. Wilner: So you had 4 different categories, and ultimately you looked at 8615 patients. This was an observational study, so you looked at their medical records?

Dr. Cavazos: Not medical records; we used medical insurance claims for partial-onset epilepsy -- a diagnosis by International Classification of Diseases, ninth edition (ICD-9), codes 345.4 or 345.5. We looked at prescription claims for the effectiveness and treatment persistence of each patient's first combination regimen. Persistence was how long the patient continued the combination therapy. Effectiveness was measured by tolerability, inferred from duration of use, and healthcare utilization during the time that the combination was used. Healthcare utilization was measured by the number of inpatient hospitalizations, emergency department visits, and clinic visits.


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