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September 23, 2020
Open AccessLetter to the Editor

Pharmacologic treatment and SUDEP risk
A nationwide, population-based, case-control study

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Olafur Sveinsson, MD, PhD https://orcid.org/0000-0002-4507-2935, Tomas Andersson, BSc, Peter Mattsson, MD, PhD, Sofia Carlsson, PhD, and Torbjörn Tomson, MD, PhDAuthors Info & Affiliations
November 3, 2020 issue
95 (18) e2509-e2518
https://doi.org/10.1212/WNL.0000000000010874
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Letters to the Editor
13 October 2020
Author response: Pharmacological treatment and SUDEP risk: A nationwide population-based case-control study
Olafur Sveinsson, MD, PhD| Karolinska Institutet (Stockholm, Sweden)
Tomas Andersson, BSc| Karolinska Institutet (Stockholm, Sweden)
Peter Mattsson, MD, PhD| University of Uppsala (Uppsala, Sweden)
Sofia Carlsson, PhD| Karolinska Institutet (Stockholm, Sweden)
Torbjörn Tomson, MD, PhD| Karolinska Institutet (Stockholm, Sweden)

We are thankful for the excellent comments made by Dr Sethi on our article.1 We have neither investigated the specific combination of lamotrigine and valproic nor the intensity of statin therapy on SUDEP risk. We are currently looking into the possibilities to make such and similar subgroup analyses, but it is clear that the interpretation of the results of such assessments will be hampered by the comparatively small numbers in each subgroup.  

Disclosure

The authors report no relevant disclosures. Contact [email protected] for full disclosures.

Reference

  1. Sveinsson O, Andersson T, Mattsson P, Carlsson S, Tomson T . Pharmacological treatment and SUDEP risk: A nationwide population-based case- control study. Neurology 2020 Epub Sep 23.
5 October 2020
Author response: Pharmacological treatment and SUDEP risk: A nationwide population-based case-control study
Olafur Sveinsson, MD, PhD| Karolinska Institutet (Stockholm, Sweden)
Tomas Andersson, BSc| Karolinska Institutet (Stockholm, Sweden)
Peter Mattsson, MD, PhD| University of Uppsala (Uppsala, Sweden)
Sofia Carlsson, PhD| Karolinska Institutet (Stockholm, Sweden)
Torbjörn Tomson, MD, PhD| Karolinska Institutet (Stockholm, Sweden)

We are grateful for the comments on our article1 from our colleagues, Anand Kumar and Neha Lall, who recognize the novel findings of our study presenting the potential protective effects of polytherapy with antiepileptic drugs and with monotherapy on SUDEP risk. Furthermore, they rightly emphasize the need for future studies exploring the possible association between statins/SSRIs and SUDEP risk.  

Disclosure

The authors report no relevant disclosures. Contact [email protected] for full disclosures.

Reference

  1. Sveinsson O, Andersson T, Mattsson P, Carlsson S, Tomson T . Pharmacological treatment and SUDEP risk: A nationwide population-based case- control study. Neurology 2020 Epub Sep 23.
27 September 2020
Reader response: Pharmacological treatment and SUDEP risk: A nationwide population-based case-control study
Anand Kumar, Neurologist| Banaras Hindu University, Institute of Medical Sciences (Varanasi, India)
Neha Lall, Doctor| Banaras Hindu University, Institute of Medical Sciences (Varanasi, India)

We read, with interest the article by Sveinsson et al.1 on Sudden Unexpected Death in Epilepsy (SUDEP). This is the largest case control population-based study with 255 cases (167 definite & 88 probable). The most important highlights of this study is that polytherapy treatment with three or more antiepileptic drugs (AEDs) is associated with reduced SUDEP risk, contrary to various previous studies which showed polytherapy itself as a risk factor.2 While previous studies have showed either negative association of AEDs or no significant association with SUEDP,3 for the first time, there is a positive correlation reported with levetiracetam. Preventive effects of non-AED drugs—like statins on SUDEP in the current study1—need to be explored for their potential benefits. Cochrane Reviews advocates further research on potential beneficial effects of selective serotonin reuptake inhibitors (SSRI).4 SSRI reduces central hypoventilation by enhancing serotonergic mechanism of respiratory regulation as one of the proposed mechanism for SUDEP in patients of epilepsy.4 Contrasting findings on SSRIs by authors need further explanation.

However, adequate seizure control with appropriate AEDs, education, and awareness regarding SUDEP remains universally accepted for patients with epilepsy. 

Disclosure

The authors report no relevant disclosures. Contact [email protected] for full disclosures.

References

  1. Sveinsson O, Andersson T, Mattsson P, Carlsson S, Tomson T . Pharmacological treatment and SUDEP risk: A nationwide population-based case- control study. Neurology 2020 Epub Sep 23.
  2. Nilsson L, Farahmand BY, Persson P, Thiblin I, Tomson T. Risk factors for sudden unexpected death in epilepsy: a case-control study. Lancet 1999;353:888–893.
  3. Devinsky O, Hesdorffer DC, Thurman DJ, Lhatoo S, Richerson G. Sudden unexpected death in epilepsy: epidemiology, mechanisms, and prevention. Lancet Neurol 2016;15:1075–1088.
  4. Maguire MJ, Jackson CF, Marson AG, Nolan SJ. Treatments for the prevention of Sudden Unexpected Death in Epilepsy (SUDEP). Cochrane Database Syst Rev 2016 Jul;7:CD011792.
25 September 2020
Reader response: Pharmacological treatment and SUDEP risk: A nationwide population-based case-control study
Nitin K. Sethi, Associate Professor of Neurology| New York-Presbyterian Hospital, Weill Cornell Medical Center (New York, NY)

I read with interest nationwide population-based case-control study by Sveinsson et al.1 looking at pharmacologic treatment and SUDEP risk and the accompanying editorial by Nashef and Rugg-Gunn.2 It is intriguing to think that it is not just the level of GTCS control but also the AEDs used to achieve that seizure control that may be protective in the context of SUDEP prevention. The hunt for rational polypharmacy has remained elusive in epilepsy but lamotrigine and valproic acid combination is generally regarded as having synergistic anticonvulsant effect. Do the authors have any data on SUDEP risk in this particular combination of AEDs? Also, was it low, moderate, or high-intensity statin therapy that was determined to be protective?

Disclosure

The authors report no relevant disclosures. Contact [email protected] for full disclosures.

References

  1. Sveinsson O, Andersson T, Mattsson P, Carlsson S, Tomson T . Pharmacological treatment and SUDEP risk: A nationwide population-based case- control study. Neurology 2020 Epub Sep 23.
  2. Nashef L, Rugg-Gunn F. Reducing the risk of SUDEP: From uncertainty to reality. Neurology. 2020 Epub Sep 23.

Information & Authors

Information

Published In

Neurology®
Volume 95 • Number 18 • November 3, 2020
Pages: e2509-e2518
PubMed: 32967928

Copyright

Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

Publication History

Received: December 23, 2019
Accepted: June 18, 2020
Published online: September 23, 2020
Published in print: November 3, 2020

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Disclosure

O. Sveinsson has received grants from GSK, personal fees from Biogen, and honoraria to his institution from Biogen and UCB for lectures and advisory board, outside the submitted work. T. Andersson and S. Carlsson report no disclosures. P. Mattsson received research support from the Uppsala County Council, CURE, Epilepsifonden, and Selander Foundation. T. Tomson is an employee of Karolinska Institutet, is associate editor of Epileptic Disorders, has received speaker's honoraria to his institution from Eisai, Sanofi, Sun Pharma, UCB, and Sandoz, and received research support from Stockholm County Council, EU, CURE, GSK, UCB, Eisai, and Bial. Go to Neurology.org/N for full disclosures.

Study Funding

The study was supported by funding from Stockholm County Council, GlaxoSmithKline, and Citizens United for Research in Epilepsy (CURE). The sponsors had no influence on the conduct of the study, analysis, interpretation, writing of the manuscript, or the decision to publish the results.

Authors

Affiliations & Disclosures

Olafur Sveinsson, MD, PhD https://orcid.org/0000-0002-4507-2935
From the Department of Neurology (O.S., T.T.), Karolinska University Hospital; Department of Clinical Neuroscience (O.S., T.T.) and Institute of Environmental Medicine (T.A., S.C.), Karolinska Institutet, Stockholm; Center for Occupational and Environmental Medicine (T.A.), Stockholm County Council; and Department of Neuroscience (P.M.), University of Uppsala, Sweden.
Disclosure
Scientific Advisory Boards:
1.
1) Advisory board for Biogen Idec on the medication Plegridy for MS.
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
1) Travel funding from Biogen Idec 2) Travel funding from UCB 3) Travel funding from Sandoz
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
1) Consultant for Biogen Idec on Plegridy and Zinbryta.
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
Received consulting fees from Biogen, other from Biogen, other from UCB and Sandoz, outside the submitted work.
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
1) The study was supported by Stockholm County Council, GlaxoSmithKline and Citizens United for Research in Epilepsy (CURE).
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
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Tomas Andersson, BSc
From the Department of Neurology (O.S., T.T.), Karolinska University Hospital; Department of Clinical Neuroscience (O.S., T.T.) and Institute of Environmental Medicine (T.A., S.C.), Karolinska Institutet, Stockholm; Center for Occupational and Environmental Medicine (T.A.), Stockholm County Council; and Department of Neuroscience (P.M.), University of Uppsala, Sweden.
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
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Peter Mattsson, MD, PhD
From the Department of Neurology (O.S., T.T.), Karolinska University Hospital; Department of Clinical Neuroscience (O.S., T.T.) and Institute of Environmental Medicine (T.A., S.C.), Karolinska Institutet, Stockholm; Center for Occupational and Environmental Medicine (T.A.), Stockholm County Council; and Department of Neuroscience (P.M.), University of Uppsala, Sweden.
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.
Meducan Limited
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.
Uppsala County Council
Research Support, Foundations and Societies:
1.
Epilepsifonden Selander Foundation CURE (with prof Tomson) Stock/Stock Options, Medical Equipment & Materials: Elekta AB
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
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NONE
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NONE
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NONE
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Sofia Carlsson, PhD
From the Department of Neurology (O.S., T.T.), Karolinska University Hospital; Department of Clinical Neuroscience (O.S., T.T.) and Institute of Environmental Medicine (T.A., S.C.), Karolinska Institutet, Stockholm; Center for Occupational and Environmental Medicine (T.A.), Stockholm County Council; and Department of Neuroscience (P.M.), University of Uppsala, Sweden.
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.
Grants from the Swedish Research Council, Swedish Diabetes Association, Swedish Research Council for social and working life (other research)
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
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1.
NONE
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1.
NONE
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NONE
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Torbjörn Tomson, MD, PhD
From the Department of Neurology (O.S., T.T.), Karolinska University Hospital; Department of Clinical Neuroscience (O.S., T.T.) and Institute of Environmental Medicine (T.A., S.C.), Karolinska Institutet, Stockholm; Center for Occupational and Environmental Medicine (T.A.), Stockholm County Council; and Department of Neuroscience (P.M.), University of Uppsala, Sweden.
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
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Notes

Correspondence Dr. Sveinsson [email protected]
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
The Article Processing Charge was funded by Karolinska Institute.

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