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Articles
February 4, 2015
Letter to the Editor

Antiepileptic drug use by pregnant women enrolled in Florida Medicaid

March 3, 2015 issue
84 (9) 944-950

Abstract

Objective:

The study aims were to investigate secular trends in antiepileptic drug (AED) use in women during pregnancy, and to compare the use of first- and second-generation AEDs.

Methods:

Study participants consisted of female Florida Medicaid beneficiaries, older than 15 years, and pregnant within the time period 1999 to 2009. Fifteen AEDs were categorized into first and second generation of AEDs. Continuous use of AEDs was defined as at least 2 consecutive AED prescriptions totaling more than a 30-day supply. Polytherapy was defined as 2 or more AEDs continuously used for at least 30 overlapping days. Annual prevalence was estimated and compared.

Results:

We included 2,099 pregnant women who were enrolled in Florida Medicaid from 1999 to 2009 and exposed to AEDs during pregnancy. Although there were fluctuations, overall AED use in the study cohort did not increase from 2000 to 2009 (β ± standard error [SE]: −0.07 ± 0.06, p = 0.31). The use of first-generation AEDs decreased (β ± SE: −6.21 ± 0.47, p < 0.0001), whereas the use of second-generation AEDs increased (β ± SE: 6.27 ± 0.52, p < 0.0001) from 2000 to 2009. AED use in polytherapy did not change through the study period. Valproate use reduced from 23% to 8% in the study population (β ± SE: −1.61 ± 0.36, p = 0.0019), but this decrease was only for women receiving an AED for epilepsy and was not present for other indications.

Conclusion:

The second-generation AEDs are replacing first-generation AEDs in both monotherapy and polytherapy. Valproate use has declined for epilepsy but not other indications. Additional changes in AED use are expected in future years.

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Letters to the Editor
24 March 2015
CHANGING SCENARIO OF ANTIEPILEPTICS IN PREGNANT FEMALES
Khichar Purnaram Shubhakaran, Associate Professor Neurology
Rekha Jakhar Khichar, Associate Professor, Gyae & Obs,Jodhpur, India

Wen et al. studied the secular trends in use of antiepileptic drugs (AED), comparing the use of first- and second- line AED drugs in pregnant females. [1] The authors found that the use of first-line AED is declining while second-line AED use is on the rise. Jette further elaborated in her comment [2] to fill the gaps in knowledge.

The authors noted less decline in the first-line AED valproate for nonepileptic use. The biggest disadvantage with valproate use is congenital malformations, but weight gain, hyperammonemic encephalopathy, and polycystic ovary syndrome are other major issues.

Second-line AED levetiracetam has also caused hyperammonemic encephalopathy increase, requiring further evaluation. [3] Studies have demonstrated the role of levetiracetam in headache, but regarding a correlation with weight gain, there are conflicting reports. Levetiracetam has not shown to negatively affect cognition, rather to improve. [4] However, further studies are warranted.

1. Wen X, Meador KJ, Hartzema A. Antiepileptic drug use by pregnant women enrolled in Florida Medicaid. Neurology 2015;84:944-950.

2. Jette N. Comment: Are we filling knowledge gaps about antiepileptic drugs and pregnancy? Neurology 2015;84:950.

3. Roh SY, Jang HS, Jeong EH. Valproic acid enduced hyperammonemic encephalopathy promoted by levetiracetam. J Epilepsy Res 2014;4:82-84.

4. Huang CW, Pai MC, Tsai JJ. Comparative cognitive effects of levetiracetam and topiramate in intractable epilepsy. Psychiatry Clin Neurosci 2008;62: 548-553.

For disclosures, please contact the editorial office at [email protected].

17 February 2015
First Vs. Second generation antiepileptic drugs
Nitin K. Sethi, Assistant Professor of Neurology

Wen et al. reported on trends in antiepileptic drug (AED) use by pregnant women enrolled in Florida Medicaid. [1] The authors found that the use of first-generation AEDs for epilepsy treatment decreased while second-generation drugs (e.g., levetiracetam and lamotrigine) increased. The higher cost of second-generation AEDs compared with first-generation drugs is a major reason for their restriction from formularies. Data show that second generation AEDs have lower risk of teratogenesis and a more favorable side-effect profile compared with first-generation drugs. While the risks of brand to generic substitution of AEDs are still unclear, generic versions of second generation AEDs are far more affordable as compared to brand name drugs. The Wen et al. study strengthens the argument for easy availability of good quality, low-cost, generic versions of second-generation AEDs so that pregnant women without insurance and even those residing in low and middle income countries can benefit.

1. Wen X, Meador KJ, Hartzema A. Antiepileptic drug use by pregnant women enrolled in Florida Medicaid. Neurology. 2015 Feb 4. [Epub ahead of print].

For disclosures, please contact the editorial office.

Information & Authors

Information

Published In

Neurology®
Volume 84Number 9March 3, 2015
Pages: 944-950
PubMed: 25653296

Publication History

Received: May 6, 2014
Accepted: November 3, 2014
Published online: February 4, 2015
Published in print: March 3, 2015

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Disclosure

X. Wen reports no disclosures relevant to the manuscript. K. Meador serves on the editorial boards of Neurology®, Behavior & Neurology, Epilepsy & Behavior, Epilepsy.com, and the Journal of Clinical Neurophysiology and on the professional advisory board for the Epilepsy Foundation; he has received travel support from Sanofi-Aventis, and received research support from GlaxoSmithKline, Eisai Inc., Marinus Pharmaceuticals, Inc., Myriad Genetics, Inc., NeuroPace, Inc., Pfizer, SAM Technology Inc., UCB Pharma, the NIH National Institute of Neurological Disorders and Stroke (2RO1-NS38455 [PI], 2U01-NS038455 [multi-PI], 1 R01 NS076665 [consultant]), the PCORI (PCORI 527 [co-PI]), and the Epilepsy Foundation. Dr. Meador has consulted for the Epilepsy Study Consortium, which receives money from multiple pharmaceutical companies (in relation to his work for Eisai, NeuroPace, Novartis, Supernus, Upsher-Smith Laboratories, UCB Pharma, and Vivus Pharmaceuticals). The funds for consulting for the Epilepsy Study Consortium were paid to his university. A. Hartzema has a consultant appointment with Pfizer not related to this study. He also has a senior advisor appointment to the FDA CDRH, and declares that the views expressed here are his personal views and not those of the FDA. Go to Neurology.org for full disclosures.

Study Funding

This work was supported in part by grant U01 NS038455 (Meador).

Authors

Affiliations & Disclosures

Xuerong Wen, PhD
From the Department of Medicine (X.W.), and Department of Pharmaceutical Outcomes and Policy, College of Pharmacy (A.H.), University of Florida, Gainesville; and Department of Neurology & Neurological Sciences (K.J.M.), Stanford University, CA.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Kimford J. Meador, MD
From the Department of Medicine (X.W.), and Department of Pharmaceutical Outcomes and Policy, College of Pharmacy (A.H.), University of Florida, Gainesville; and Department of Neurology & Neurological Sciences (K.J.M.), Stanford University, CA.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
Travel support from Sanofi-Aventis (maker of valproate) to lecture in 2010 on effects of fetal exposure to antiepileptic drugs at epilepsy symposium
Editorial Boards:
1.
Neurology, Epilepsy & Behavior, Cognition & Behavioral Neurology
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
Dr. Meador has acted as a consultant for the Epilepsy Study Consortium that receives money from multiple pharmaceutical companies; Dr. Meador has received salary support to his university from the Epilepsy Consortium for research consultant work related for Eisai, NeuroPace, Novartis, Supernus, Upsher Smith Laboratories, UCB Pharma and Vivus Pharmaceuticals.
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
Clinical care of patients with epilepsy.
Research Support, Commercial Entities:
1.
Dr. Meador reports receiving active research support from UCB Pharma, and receiving past research support from Pfizer in the last 2 years.
Research Support, Government Entities:
1.
Dr. Meador is receiving active research support for NIH/NINDS 2-U01-NS038455-11 Meador (Multi-PI) Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs; NIH/NINDS 1 R01 NS076665-01 Meador (Consultant) Characterizing and Predicting Drug Effects on Cognition; NIH/NINDS #1U01NS077366-03 Meador (Co-I) Emory Clinical Research Site for NIH NEXT; PCORI Meador (Co-PI) Cognitive AED Outcomes in Pediatric Localization Related Epilepsy (COPE).
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Abraham Hartzema, PhD
From the Department of Medicine (X.W.), and Department of Pharmaceutical Outcomes and Policy, College of Pharmacy (A.H.), University of Florida, Gainesville; and Department of Neurology & Neurological Sciences (K.J.M.), Stanford University, CA.
Disclosure
Scientific Advisory Boards:
1.
Pfizer: Active Surveillance Expert Panel United States Pharmacopeia, Council of experts, Nomenclature, Safety, and labeling 2010-2015. FDA CDRH Senior Advisor 2013-current
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
Pharmaceutical Research, 1995 ? 1997 International Journal of Pharmacy Practice, 1998- Mahidol University Journal of Pharmaceutical Sciences 1/1/2005 -
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE

Notes

Correspondence to Dr. Wen: [email protected]
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

Author Contributions

Dr. Xuerong Wen: drafting/revising the manuscript for content, study concept or design, analysis or interpretation of data, acquisition of data, statistical analysis. Dr. Kimford Meador: drafting/revising the manuscript for content, study concept or design, interpretation of data, obtaining funding. Dr. Abraham Hartzema: drafting/revising the manuscript for content, study concept or design, and interpretation of data.

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