Effects of antiepileptic drug substitutions on epileptic events requiring acute care.

Study Objectives: To determine the odds of antiepileptic drug substitution among patients who had an epileptic event requiring acute care-ambulance service, emergency department visit, or hospitalization-relative to patients who did not have an event, and to compare these results with those from a recent study involving a similar method but different patients.

Design: Case-control analysis.

Data Source: United States health care claims from the PharMetrics database.

Patients: A cohort of patients aged 12-64 years with a primary diagnosis of epilepsy between October 1, 2005, and December 31, 2006; 991 cases (patients who experienced an epileptic event requiring acute care) and 2973 controls (patients who did not have an event) were matched in a 1:3 ratio for sex, age, and type of epilepsy.

Measurements And Main Results: Using discordant pairs analysis, we calculated the odds ratio of an epileptic event that required acute care occurring in patients whose antiepileptic drug underwent substitution to an A-rated (therapeutically equivalent) alternative (switch from branded product to generic, generic to branded, or generic to generic) versus those whose drugs were not substituted. For matched data, 109 (11.0%) of 991 cases had an A-rated antiepileptic drug substitution in the 6 months before the event, whereas only 186 (6.3%) of 2973 controls had a substitution (odds ratio 1.84, 95% confidence interval 1.44-2.36). Our results were similar to those of a previous study involving a different patient database, which showed substitution rates of 11.3% for cases versus 6.5% for controls (odds ratio 1.81, 95% confidence interval 1.25-2.63). Our sensitivity analyses were robust, and we found a temporal relationship in that numerous substitutions occurred in the month before the acute event.

Conclusion: Patients who had an epileptic event requiring acute care were about 80% more likely than matched controls without an acute event to have recently had an antiepileptic drug substitution. Our replication of a previously published case-control analysis revealed a similar association between substitution involving A-rated antiepileptic drugs and subsequent epileptic events requiring acute care, thereby lending credibility to the findings.