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April 26, 2022; 98 (17) Research Article

Sudden Death and Cardiac Arrythmia With Lamotrigine

A Rapid Systematic Review

Johanna W. Bunschoten, Nafisa Husein, Orrin Devinsky, Jacqueline A. French, Josemir W. Sander, Roland D. Thijs, Mark R. Keezer
First published March 8, 2022, DOI: https://doi.org/10.1212/WNL.0000000000200164
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Article Information

vol. 98 no. 17 e1748-e1760
DOI: 
https://doi.org/10.1212/WNL.0000000000200164
PubMed: 
35260442
Published By: 
Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology
Print ISSN: 
0028-3878
Online ISSN: 
1526-632X
History: 
  • Received August 6, 2021
  • Accepted in final form January 21, 2022
  • First Published March 8, 2022.

Article Versions

Copyright & Usage: 
© 2022 American Academy of Neurology

Author Disclosures

    1. Johanna W. Bunschoten, MSc*,
    2. Nafisa Husein, MSc*,
    3. Orrin Devinsky, MD,
    4. Jacqueline A. French, MD,
    5. Josemir W. Sander, MD, PhD, FRCP,
    6. Roland D. Thijs, MD, PhD, FRCP and
    7. Mark R. Keezer, MDCM, PhD
  1. Johanna W. Bunschoten, MSc*,
    2. 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

  2. Nafisa Husein, MSc*,
    3. 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

  3. Orrin Devinsky, MD,
    4. 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. <br>Cognitive and Behavioral Neurology; Oxford University <br>Press, 2002<br>Epilepsy: Patient and Family Guide, Demos Press, 2008<br>Alternative Therapies for Epilepsy, Demos Press, 2012<br>Epilepsy In Children, Demos Press, 2015<br>

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. <br>I have consulted for Marinus, Ultragenyx, BridgeBio, Xenon and ZOgenix <br>and The Center for Discovery<br>

    Speakers' Bureaus:

    1. NONE

    Other activities:

    1. <br>Scientific Advisory Board and/or Equity Interest for Estate <br>biosciences, Tevard, <br>Egg Rock, Engage, Script biosciences, Regel Biosciences, <br>Empatica, Rettco, <br>Receptor Life Sciences, California <br>Cannabis Enterprises, SilverSpike and Tilray.<br>Principal Investigator, North American SUDEP Registry and <br>Sudden Unexplained Childhood Death Registry and Research <br>Collaborative<br>Funded by NINDS, NIMH, Dept of Defense, CDC<br>

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. <br>For research support:<br>GW Pharmaceuticals<br>Novartis<br>Marinus<br>Eisai<br>Zogenix<br>Ovid Pharma<br>Silver Spike <br>Epilepsy Foundation<br>Script Therapeutics<br>Regel Therapeutics<br>

    Research Support, Government Entities:

    1. <br>Ongoing Support<br><br>NIH R01 R01MH111417 (PI: N Petridou) <br>9/22/2016 – 6/30/2021 <br>Development and validation of empirical models of the <br>neuronal population <br>activity underlying non-invasive human brain measurements<br>The aims of this project are 1) Characterize, model and <br>quantify the exact <br>electrophysiological response of neuronal populations to <br>external stimulation, 2) <br>Characterize, model and quantify the exact haemodynamic <br>response in single <br>voxels to external stimulation, 3) Build comprehensive and <br>integrative models <br>linking stimuli to a) neuronal population <br>electrophysiological activity and b) <br>haemodynamic signals, in order to accurately relate <br>haemodynamics measures <br>to neuronal population activity.<br>Role: Co-Investigator<br><br><br>NIH 1RF1MH116978 (PI: E Yacoub) <br>9/1/2018 – 8/30/2022<br>Neural and vascular underpinnings of laminar fMRI in humans<br>The three aims to this project are 1) validate laminar fMRI <br>against laminar <br>electrophysiology in humans to create a neurovascular <br>coupling model using an <br>oddball paradigm, 2) generalize the neurovascular coupling <br>model to a novel, <br>cross-modal associative learning task, 3) generalize the <br>laminar-fMRI model <br>developed in Aim 1 and 2 to networks of brain regions and <br>validate the results <br>against intracranial electrophysiological signals measured <br>in human subjects in <br>an audio/visual associative learning task.<br><br>NIH U24NS113847 (PI: L Doan) <br>7/1/2019 – 6/30/2024<br>EPPIC-NET<br>The Data Coordinating Center (DCC) of the EPPIC-Net, in <br>close collaboration <br>with the network’s Clinical<br>Coordinating Center (CCC), the Specialized Clinical Centers <br>(SCCs), HEAL, and <br>government partners, will provide statistical and data <br>management expertise for <br>conducting high-quality efficient studies for developing <br>non-addictive <br>treatments for pain. In addition, it will compile a <br>collection of clinical and <br>biomarker data and establish a repository for biospecimens. <br>These resources <br>will be linked and shared with the community of pain<br>researchers.<br>

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. NONE

    Stock/Stock Options/Board of Directors Compensation:

    1. <br>Rettco - Stock<br>Tevard - Stock<br>Engage - Stock<br>Qstate - Stock<br>Tilray - Stock Options<br>Leafly - Stock<br>Docklight - Stock<br>Left coast ventures - Stock<br>California Cannabis Enterprises - stock<br>Receptor Life Sciences - Stock<br>Egg Rock - Stock<br>Empatica - Stock<br>SilverSpike - Stock<br>Regel Biosciences - stock<br>Script biosciences - Stock<br> Signature: Orrin Devinsky Date: Jan 3, 2022<br><br>

    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

  4. Jacqueline A. French, MD,
    5. Scientific Advisory Boards:

    1. <br>On the scientific advisory board or consultant for <br>Adamas, Aeonian/Aeovian, Alterity Therapeutics Limited, Anavex, Arkin Holdings, Arvelle Therapeutics, Inc., Athenen Therapeutics/Carnot Pharma, Autifony Therapeutics Limited, Baergic Bio, Biogen, BioMarin Pharmaceutical Inc., BioXcel Therapeutics, Bloom Science Inc., BridgeBio Pharma Inc., Cavion, Cerebral Therapeutics, Cerevel, Clinical Education Alliance, Corlieve Therapeutics, Crossject, CuroNZ, Eisai, Eliem Therapeutics, Encoded Therapeutics, Engage Therapeutics, Engrail, Epalex, Epihunter, Epiminder, Equilibre BioPharmaceuticals, Fortress Biotech, Greenwich Biosciences, GW Pharma, Janssen Pharmaceutica, Knopp Biosciences, LivaNova, Longboard Pharmaceuticals, Lundbeck, Marinus, Mend Neuroscience, Merck, NeuCyte Inc., Neumirna Therapeutics, Neurocrine, Neuropace, NxGen Medicine Inc., Ono Pharmaceutical Co., Otsuka Pharmaceutical Development, Ovid Therapeutics Inc., Passage Bio, Pfizer, Praxis, PureTech LTY Inc., Redpin, Sage, SK Life Sciences, Sofinnova, Stoke, Supernus, Synergia Medical, Takeda, UCB Inc., West Therapeutic Development, Xenon, Xeris, Zogenix, Zynerba<br>

    Gifts:

    1. NONE

    Funding for travel or speaker honoraria:

    1. <br>Paid travel to present findings at scientific <br>meetings, present at investigators meetings attend <br>advisory boards or give lectures from the Epilepsy Study Consortium, the Epilepsy Foundation, Arvelle Therapeutics, Inc., Biogen, Cerevel, Engage, Lundbeck, NeuCyte, Inc., Otsuka, Sage, UCB, Xenon, Zogenix.<br>

    Editorial Boards:

    1. <br>2) Lancet Neurology,Editorial Board, 3 years<br>3) Neurology Today, Editorial board 3 years<br>

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. <br>President, Epilepsy Study Consortium, that recieves money<br>from multiple pharmaceutical companies. I consult for a<br>number of companies, on behalf of the Epilepsy Study<br>consortium. A fixed 40% of my NYU salary is paid by the<br>study consortium, and some of this money may come from<br>consulting fees. Companies involved include Adamas, Aeonian/Aeovian, Alterity Therapeutics Limited, Anavex, Arkin Holdings, Arvelle Therapeutics, Inc., Athenen Therapeutics/Carnot Pharma, Autifony Therapeutics Limited, Baergic Bio, Biogen, BioMarin Pharmaceutical Inc., BioXcel Therapeutics, Bloom Science Inc., BridgeBio Pharma Inc., Cavion, Cerebral Therapeutics, Cerevel, Clinical Education Alliance, Corlieve Therapeutics, Crossject, CuroNZ, Eisai, Eliem Therapeutics, Encoded Therapeutics, Engage Therapeutics, Engrail, Epalex, Epihunter, Epiminder, Equilibre BioPharmaceuticals, Fortress Biotech, Greenwich Biosciences, GW Pharma, Janssen Pharmaceutica, Knopp Biosciences, LivaNova, Longboard Pharmaceuticals, Lundbeck, Marinus, Mend Neuroscience, Merck, NeuCyte Inc., Neumirna Therapeutics, Neurocrine, Neuropace, NxGen Medicine Inc., Ono Pharmaceutical Co., Otsuka Pharmaceutical Development, Ovid Therapeutics Inc., Passage Bio, Pfizer, Praxis, PureTech LTY Inc., Redpin, Sage, SK Life Sciences, Sofinnova, Stoke, Supernus, Synergia Medical, Takeda, UCB Inc., West Therapeutic Development, Xenon, Xeris, Zogenix, Zynerba<br>Chief Medical/Innovation Officer of the Epilepsy Foundation<br>

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. <br>1) Eisai<br>2) GW Pharma<br>3) Lundbeck<br>4) SK Life Sciences<br>5) Neurelis<br>6) UCB<br>7) Zogenix<br>8) Cerevel<br>9) Xenon<br>10) Sunovion<br>11) Pfizer<br>12) GW Pharmaceuticals<br>13) One8 Foundation<br>14)Faces<br>

    Research Support, Government Entities:

    1. <br>NIH 2U01NS038455-16A1 K Meador (PI) 8/1/12 – 2/28/23<br>Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs<br>This is a multicenter study assessing outcomes of pregnancy in women with epilepsy.<br>Role: Co-Investigator<br>

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. <br>1) Epilepsy Research Foundation<br>2) Epilepsy Study Consortium<br> Signature: /Jacqueline French/ Date: 03/01/2022<br><br>

    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

  5. Josemir W. Sander, MD, PhD, FRCP,
    6. Scientific Advisory Boards:

    1. <br>1) UCB Pharma - membership of Advisory Board<br>2) Zobenix - membership of Advisory Board<br>3) Arvelle - membership of Advisory Board<br>

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. <br>1) Lancet Neurology - member of Editorial Board<br>

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. <br>1) UCB Pharma - membership of Speakers' Bureau<br>2) Zogenix - membership of Speakers' Bureau<br>3) Eisai - membership of Speakers' Bureau<br>4) Arvelle - membership of Speakers' Bureau<br>

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. <br>1) UCB Pharma - research grant to my department<br> Signature: /leysander/ Date: 03/01/2022<br><br>

    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

  6. Roland D. Thijs, MD, PhD, FRCP and
    7. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for travel or speaker honoraria:

    1. <br>Medtronic: speakers and travel <br>honorarium<br>UCB: speakers honorarium<br>Zogenix: speakers honorarium<br>

    Editorial Boards:

    1. <br>Epilepsia, editorial board, 2020-now<br>Seizure, editorial board, 2014-now<br>Clinical Autonomic Research, editorial board, 2014-now<br>

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. <br>Arvelle, Theravance<br>

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. <br>(1) Medtronic Inc.<br>(2) New Life Wearables<br>

    Research Support, Government Entities:

    1. NONE

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. <br>(1) Christelijke Vereniging voor de Verpleging van Lijders aan <br>Epilepsie<br>(2) The Netherlands Organisation for Health <br>Research and Development (ZonMW; 843002707)<br> Signature: /Roland Thijs/ Date: 01/04/2022<br><br>

    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

  7. Mark R. Keezer, MDCM, PhD
    8. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. <br>Epilepsia<br>

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other activities:

    1. <br>Unrestricted educational grants from UCB and Eisai.<br>

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. <br>Research grants for investigator-initiated studies from UCB <br>and Eisai.<br>

    Research Support, Government Entities:

    1. <br>(1) Canadian Institutes of Health Research (CIHR), 408419, <br>co-PI, 2019-2021, (2) Fondation de Recherche du Quebec <br>(FRQS), KEEMA1151, J1 clinician-investigator award, 2020-<br>2024.<br>

    Research Support, Academic Entities:

    1. <br>Savoy Foundation, Canadian Frailty Network, CRCHUM, CHUM<br>Epilepsy Group, Réseau Bio-imagerie du Québec<br>

    Research Support, Foundations and Societies:

    1. <br>Fondation du Jardin de l'Arbre de la Vie, Fondation du <br>CHUM, TSC Alliance<br> Signature: Mark Keezer Date: 3 Jan 2022

    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

  1. From the Stichting Epilepsie Instellingen Nederland (SEIN) (J.W.B., J.W.S., R.D.T., M.R.K.), Heemstede; Department of Neurology (J.W.B., R.D.T.), Leiden University Medical Centre, the Netherlands; School of Public Health (N.H., M.R.K.) and Department of Neurosciences (M.R.K.), Université de Montréal, Canada; Department of Neurology (O.D., J.A.F.), New York University Grossman School of Medicine and NYU Langone Health, New York; UCL Queen Square Institute of Neurology (J.W.S., R.D.T.), London; and Chalfont Centre for Epilepsy (J.W.S., R.D.T.), Chalfont St Peter, UK.
  1. Correspondence
    Dr. Keezer mark.keezer{at}umontreal.ca
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