Background: The automatic substitution of bioequivalent generics for brand-name antiepileptic drugs (AEDs) has been linked by anecdotal reports to loss of seizure control.
Objective: To evaluate studies comparing brand-name and generic AEDs, and determine whether evidence exists of superiority of the brand-name version in maintaining seizure control.
Data Sources: English-language human studies identified in searches of MEDLINE, EMBASE and International Pharmaceutical Abstracts (1984 to 2009).
Study Selection: Randomized controlled trials (RCTs) and observational studies comparing seizure events or seizure-related outcomes between one brand-name AED and at least one alternative version produced by a distinct manufacturer.
Data Extraction: We identified 16 articles (9 RCTs, 1 prospective non-randomized trial, 6 observational studies). We assessed characteristics of the studies and, for RCTs, extracted counts for patients whose seizures were characterized as ‘controlled’ and ‘uncontrolled’.
Data Synthesis: Seven RCTs were included in the meta-analysis. The aggregate odds ratio (n = 204) was 1.1 (95% CI 0.9, 1.2), indicating no difference in the odds of uncontrolled seizure for patients on generic medications compared with patients on brand-name medications. In contrast, the observational studies identified trends in drug or health services utilization that the authors attributed to changes in seizure control.
Conclusions: Although most RCTs were short-term evaluations, the available evidence does not suggest an association between loss of seizure control and generic substitution of at least three types of AEDs. The observational study data may be explained by factors such as undue concern from patients or physicians about the effectiveness of generic AEDs after a recent switch. In the absence of better data, physicians may want to consider more intensive monitoring of high-risk patients taking AEDs when any switch occurs.
Generic Drug Seizure Control Health Service Utilization Generic Substitution Seizure Outcome
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The authors would like to thank our colleagues Edward Bromfield, MD (now deceased) and Jong Woo Lee, MD, PhD for their comments on a previous version of this article.Dr Kesselheim is supported by a career development award from the Agency for Healthcare Research and Quality (K08HS18465-01). Dr Gagne is supported by a National Institute on Aging training grant (T32 Ag000158). Dr Brookhart has received investigator-initiated grant support from Amgen Inc. for an unrelated project. Dr Shrank has received research grants from Express Scripts, CVS Caremark and Aetna. No sources of funding were used to assist in the preparation of this study. The remaining authors have no conflicts of interest that are directly relevant to the content of this study.
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