Summary:Purpose: Compulsory generic substitution of antiepileptic drugs (AEDs) may lead to adverse effects in epilepsy patients because of seizure recurrence or increased toxicity. The study objectives were (a) to quantify and compare the switchback rates from generic to brand-name AEDs versus nonAEDs, and (b) to assess clinical implications of switching from branded Lamictal to generic lamotrigine (LTG) and whether signals exist suggesting outcome worsening.Methods: By using a public-payer pharmacy-claims database from Ontario, Canada, switchback rates from generic to branded AEDs [Lamictal, Frisium (clobazam; CLB), and Depakene (VPA; divalproex)] were calculated and compared with non-AED long-term therapies, antihyperlipidemics and antidepressants, in January 2002 through March 2006. We then assessed pharmacy utilization and AED dosage among LTG patients switching back to branded Lamictal compared with those staying on generic formulation. Results:The 1,354 patients (403 monotherapy, 951 polytherapy) were prescribed generic LTG, of whom 12.9% switched back to Lamictal (11.7% monotherapy, 13.4% polytherapy). Switchback rates of other AEDs were ∼20% for CLB and VPA. The switchback rates for AEDs were substantially higher than for non-AEDs (1.5-2.9%). Significant increases in LTG doses were observed after generic substitution for those who did not switch back (6.2%; p < 0.0001). The average number of codispensed AEDs and non-AED drugs significantly increased (p < 0.0001) after LTG generic entry, especially in the generic group.Conclusions: These results reflect poor acceptance of switching AEDs to generic compounds. They may also indicate increased toxicity and/or loss of seizure control associated with generic AED use.

A higher propensity to switch back to branded medications was observed among antiepileptic drug users compared to users of antihypertensives and antihyperlipidemics, similar to findings from Andermann et al. Switch to generic lamotrigine was significantly associated with increased physician visits and hospitalizations.

Uncontrolled epilepsy in patients requiring ED visit or hospitalization was associated with significantly greater health care resource utilization and increased direct and indirect costs compared to well-controlled epilepsy in both publicly and privately insured settings.

Multiple-generic substitution of topiramate was significantly associated with negative outcomes, such as hospitalizations and injuries, and increased health care costs.

Generic antiepileptic drug use was associated with significantly greater medical utilization and risk of epilepsy-related medical events, compared to brand use. This relationship was observed even in patients characterized as stable. AED = antiepileptic drug; CI = confidence interval; ER = emergency room; HR = hazard ratio; ICD = International Classification of Diseases; IRR = incidence rate ratio.