Second Generation Anti-epileptic Drugs, Active Management Improve Some Outcomes in Epilepsy


Researchers question the belief that first generation anti-epileptic drugs are as effective as second generation drugs.

Use of second generation antiepileptic drugs (AEDs) may decrease hospital encounters by 31% in epilepsy patients, compared to the use of first generation AEDs, according to a recently published study.1 Active management and treatment by a neurologist may also improve outcomes, the study found.

Over 2 million people in the US suffer from epilepsy,2 yet 45% of these may not be adequately controlled on AEDs.3 Though first generation AEDs (available before 1993) are commonly thought to have similar efficacy as second generation AEDs (available from 1993 until September 2011), the latter may be more easily tolerated in terms of side effects and other management issues.4

In order to assess the influence of AED use on hospital encounters, senior author Patty Fritz, MS, of UCB Pharma and colleagues at Emory University School of Medicine and The University of Texas performed a retrospective analysis using a claims-based database, and validated their findings using a second claims-based database. Both databases were representative of the US population, and included claims from commercial and government insurance plans from November 2009 to September 2011. The researchers identified epilepsy cases using anti-epileptic drug use and epilepsy diagnosis coding, and considered epilepsy-related hospitalizations and emergency department visits as a proxy for negative outcomes. The analysis included 196,000 people with confirmed epilepsy, 6000 inpatient hospitalizations, and 9500 emergency department visits.

Results showed:

• Use of ≥1 first-generation AED resulted in an epilepsy-related hospital encounter every 684 days (22.8 months), while use of ≥1 second-generation AED resulted in an epilepsy-related hospital encounter every 1001 days (33.4 months) (relative risk reduction 31%, p<0.01).

• Use of second generation AEDs had a greater impact on epilepsy-related hospital encounters among sicker patients with more comorbidities (relative risk reduction 23% for a Charlson Comorbidity Index of 0, and 50% for a Charlson Comorbidity Index ≥ 10).

• Neurologists and physicians near an epilepsy center prescribed second generation AEDs more often than primary care physicians.

• Deliberate provider attempts to change medications after a hospital encounter resulted in better outcomes (relative risk reduction 18.4% [p<0.01] after a therapy modification).

• The largest benefit occurred among those who switched from a first-generation AED to a second generation AED (relative risk reduction of 26.7%, p<0.01).

Explanations for these findings could include better efficacy among second generation AEDs, as well as fewer side effects and ease of use among second generation AEDs, the authors mentioned. Alternatively, socioeconomic disparities in the use of first and second generation AEDs could play a role. Finally, patients using first generation AEDs may have more serious illness or more comorbidities, which could result in worse outcomes in this group.

“Active management of epilepsy makes a difference,” wrote Fritz and colleagues, “From our data, the rationale for the recommendation for referral to a neurologist if seizures are not promptly controlled is clear.”

“[S]econd-generation AEDs and active management of drug therapy reduce epilepsy-related hospital encounters, a major consideration for both patient safety and societal costs,” they emphasized.

Take-home Points:

• Use of second generation antiepileptic drugs (AEDs) may decrease hospital encounters by 31%, compared to the use of first generation AEDs.

• Active management and treatment by a neurologist may also improve epilepsy outcomes.

• Sicker patients with more comorbidities may derive more benefit from using second generation AEDs.

The study was funded by UCB Pharma.


Faught E, et al. Newer antiepileptic drug use and other factors decreasing hospital encounters. Epilepsy Behav. 2015 Apr;45:169-175.

National Epilepsy Foundation. About Epilepsy:  The Basics. Accessed 7 July 2015 at

Kobau R, et al. Epilepsy surveillance among adults--19 States, Behavioral Risk Factor Surveillance System, 2005. MMWR Surveill Summ. 2008 Aug 8;57(6):1-20.

Beghi E, et al. The use of recently approved antiepileptic drugs: use with caution, use in refractory patients or use as first-line indications? Expert Rev Neurother. 2011 Dec;11(12):1759-1767.

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