Drugs

, Volume 70, Issue 5, pp 605–621

Seizure Outcomes Following the Use of Generic versus Brand-Name Antiepileptic Drugs

A Systematic Review and Meta-Analysis
  • Aaron S. Kesselheim
  • Margaret R. Stedman
  • Ellen J. Bubrick
  • Joshua J. Gagne
  • Alexander S. Misono
  • Joy L. Lee
  • M. Alan Brookhart
  • Jerry Avorn
  • William H. Shrank
Original Research Article

Abstract

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.

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Copyright information

© Adis Data Information BV 2010

Authors and Affiliations

  • Aaron S. Kesselheim
    • 1
  • Margaret R. Stedman
    • 1
  • Ellen J. Bubrick
    • 2
  • Joshua J. Gagne
    • 1
  • Alexander S. Misono
    • 1
  • Joy L. Lee
    • 1
  • M. Alan Brookhart
    • 3
  • Jerry Avorn
    • 1
  • William H. Shrank
    • 1
  1. 1.Division of Pharmacoepidemiology and Pharmacoeconomics, Department of MedicineBrigham and Women’s Hospital and Harvard Medical SchoolBostonUSA
  2. 2.Division of Epilepsy, Department of NeurologyBrigham and Women’s Hospital and Harvard Medical SchoolBostonUSA
  3. 3.Department of EpidemiologyUNC Gillings School of Global Public HealthChapel HillUSA

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