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Do antiepileptic drugs or generalized tonic–clonic seizure frequency increase SUDEP risk? A combined analysis

  1. Dale C. Hesdorffer1,
  2. Torbjorn Tomson2,
  3. Emma Benn2,
  4. Josemir W. Sander3,4,
  5. Lena Nilsson5,
  6. Yvonne Langan3,
  7. Thaddeus S. Walczak6,
  8. Ettore Beghi7,
  9. Martin J. Brodie8,
  10. W. Allen Hauser1,9,
  11. for the ILAE Commission on Epidemiology; Subcommission on Mortality

Article first published online: 22 DEC 2011

DOI: 10.1111/j.1528-1167.2011.03354.x

Issue

Epilepsia

Epilepsia

Volume 53, Issue 2, pages 249–252, February 2012

Additional Information

How to Cite

Hesdorffer, D. C., Tomson, T., Benn, E., Sander, J. W., Nilsson, L., Langan, Y., Walczak, T. S., Beghi, E., Brodie, M. J., Hauser, W. A. and for the ILAE Commission on Epidemiology; Subcommission on Mortality (2012), Do antiepileptic drugs or generalized tonic–clonic seizure frequency increase SUDEP risk? A combined analysis. Epilepsia, 53: 249–252. doi: 10.1111/j.1528-1167.2011.03354.x

Author Information

  1. 1

    Department of Epidemiology, GH Sergievsky Center, Columbia University, New York, New York, U.S.A.

  2. 2

    Department of Neurology, Karolinska Institutet, Stockholm, Sweden

  3. 3

    UCL Institute of Neurology, Queen Square, London, United Kingdom

  4. 4

    SEIN – Epilepsy Institute in the Netherlands Foundation, Heemstede, The Netherlands

  5. 5

    Department of Neurological Rehabilitation, Stora Sköndal Hospital, Stockholm, Sweden

  6. 6

    Department of Neurology, University of Minnesota, Minneapolis, Minnesota, U.S.A.

  7. 7

    Laboratory of Neurological Disorders, Institute for Pharmacological Research “Mario Negri” Milan, Italy

  8. 8

    Department of Neurology and Clinical Pharmacology, University of Glasgow, Glasgow, Scotland

  9. 9

    Department of Neurology, GH Sergievsky Center, Columbia University, New York, New York, U.S.A.

*Address correspondence to Dale C. Hesdorffer, GH Sergievsky Center, Columbia University, 630 West 168th Street, P & S Unit 16, New York, NY 10032, U.S.A. E-mail: dch5@columbia.edu

  1. This report was written by experts selected by the International League Against Epilepsy (ILAE) and was approved for publication by the ILAE. Opinions expressed by the authors, however, do not necessarily represent official policy or position of the ILAE.

Publication History

  1. Issue published online: 26 JAN 2012
  2. Article first published online: 22 DEC 2011
  3. Accepted October 26, 2011; Early View publication December 22, 2011.

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Keywords:

  • SUDEP;
  • Epilepsy;
  • Case–control study;
  • Antiepileptic drugs;
  • Generalized tonic–clonic seizures frequency

Summary

Purpose:  In an analysis of four case–control studies of sudden unexpected death in epilepsy (SUDEP), we found that yearly frequency of generalized tonic–clonic seizures (GTCS) and antiepileptic drug (AED) polytherapy were associated with an increased risk for SUDEP. The prior analysis, however, did not evaluate AEDs and GTCS frequency concurrently.

Methods:  We combined data from the three case–control studies with information on the frequency of GTCS and AED therapy, that is, carbamazepine, phenytoin, valproic acid, and other AED therapy. Number of AEDs was also considered. Lamotrigine and GTCS frequency were considered separately in two of the case–control studies. Logistic regression analysis was used to evaluate GTCS frequency, each of the AEDs, and number of AEDs. Adjusted analysis of the different AEDs accounted for study, age at death, gender, and GTCS frequency.

Key Findings:  In crude analysis, GTCS frequency, AED polytherapy, and number of AEDs were associated with an increased risk for SUDEP. Analysis of individual AEDs and of number of AEDs, adjusting for GTCS frequency, revealed no increased risk associated with AEDs as monotherapy, polytherapy, or total number. GTCS frequency remained strongly associated with an increased risk for SUDEP.

Significance:  Our findings—that none of the AEDs considered were associated with increased SUDEP risk as monotherapy or as polytherapy when GTCS frequency was taken into account—provide a consistent message that number of GTCS increases SUDEP risk and not AEDs. These results suggest that prevention of SUDEP must involve increased efforts to decrease GTCS frequency in order to avert the occurrence of this devastating epilepsy outcome.

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