Risk of sudden unexpected death in epilepsy (SUDEP) with lamotrigine and other sodium channel‐modulating antiseizure medications
Abstract Objective In vitro data prompted U.S Food and Drug Administration warnings that lamotrigine, a common sodium channel modulating anti‐seizure medication (NaM‐ASM), could increase the risk of sudden death in patients with structural or ischaemic cardiac disease, however, its implications for...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2023-06-01
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| Series: | Epilepsia Open |
| Online Access: | https://doi.org/10.1002/epi4.12693 |
| _version_ | 1797813778553765888 |
|---|---|
| author | Russell Nightscales Sarah Barnard Juliana Laze Zhibin Chen Gerard Tao Clarissa Auvrez Shobi Sivathamboo Mark J. Cook Patrick Kwan Daniel Friedman Samuel F. Berkovic Wendyl D'Souza Piero Perucca Orrin Devinsky Terence J. O'Brien |
| author_facet | Russell Nightscales Sarah Barnard Juliana Laze Zhibin Chen Gerard Tao Clarissa Auvrez Shobi Sivathamboo Mark J. Cook Patrick Kwan Daniel Friedman Samuel F. Berkovic Wendyl D'Souza Piero Perucca Orrin Devinsky Terence J. O'Brien |
| author_sort | Russell Nightscales |
| collection | DOAJ |
| description | Abstract Objective In vitro data prompted U.S Food and Drug Administration warnings that lamotrigine, a common sodium channel modulating anti‐seizure medication (NaM‐ASM), could increase the risk of sudden death in patients with structural or ischaemic cardiac disease, however, its implications for Sudden Unexpected Death in Epilepsy (SUDEP) are unclear. Methods This retrospective, nested case–control study identified 101 sudden unexpected death in epilepsy (SUDEP) cases and 199 living epilepsy controls from Epilepsy Monitoring Units (EMUs) in Australia and the USA. Differences in proportions of lamotrigine and NaM‐ASM use were compared between cases and controls at the time of admission, and survival analyses from the time of admission up to 16 years were conducted. Multivariable logistic regression and survival analyses compared each ASM subgroup adjusting for SUDEP risk factors. Results Proportions of cases and controls prescribed lamotrigine (P = 0.166), one NaM‐ASM (P = 0.80), or ≥2NaM‐ASMs (P = 0.447) at EMU admission were not significantly different. Patients taking lamotrigine (adjusted hazard ratio [aHR] = 0.56; P = 0.054), one NaM‐ASM (aHR = 0.8; P = 0.588) or ≥2 NaM‐ASMs (aHR = 0.49; P = 0.139) at EMU admission were not at increased SUDEP risk up to 16 years following admission. Active tonic–clonic seizures at EMU admission associated with >2‐fold SUDEP risk, irrespective of lamotrigine (aHR = 2.24; P = 0.031) or NaM‐ASM use (aHR = 2.25; P = 0.029). Sensitivity analyses accounting for incomplete ASM data at follow‐up suggest undetected changes to ASM use are unlikely to alter our results. Significance This study provides additional evidence that lamotrigine and other NaM‐ASMs are unlikely to be associated with an increased long‐term risk of SUDEP, up to 16 years post‐EMU admission. |
| first_indexed | 2024-03-13T07:57:48Z |
| format | Article |
| id | doaj.art-1dae4077d38c41c78a910a4a7028fd91 |
| institution | Directory Open Access Journal |
| issn | 2470-9239 |
| language | English |
| last_indexed | 2024-03-13T07:57:48Z |
| publishDate | 2023-06-01 |
| publisher | Wiley |
| record_format | Article |
| series | Epilepsia Open |
| spelling | doaj.art-1dae4077d38c41c78a910a4a7028fd912023-06-02T03:50:17ZengWileyEpilepsia Open2470-92392023-06-018233434510.1002/epi4.12693Risk of sudden unexpected death in epilepsy (SUDEP) with lamotrigine and other sodium channel‐modulating antiseizure medicationsRussell Nightscales0Sarah Barnard1Juliana Laze2Zhibin Chen3Gerard Tao4Clarissa Auvrez5Shobi Sivathamboo6Mark J. Cook7Patrick Kwan8Daniel Friedman9Samuel F. Berkovic10Wendyl D'Souza11Piero Perucca12Orrin Devinsky13Terence J. O'Brien14Department of Neuroscience, Central Clinical School Monash University Melbourne Victoria AustraliaDepartment of Neuroscience, Central Clinical School Monash University Melbourne Victoria AustraliaDepartment of Neurology New York University Grossman School of Medicine New York New York USADepartment of Neuroscience, Central Clinical School Monash University Melbourne Victoria AustraliaDepartment of Medicine (The Royal Melbourne Hospital) The University of Melbourne Melbourne Victoria AustraliaDepartment of Neurology The Royal Melbourne Hospital Melbourne Victoria AustraliaDepartment of Neuroscience, Central Clinical School Monash University Melbourne Victoria AustraliaDepartment of Medicine St. Vincent's Hospital, The University of Melbourne Fitzroy Victoria AustraliaDepartment of Neuroscience, Central Clinical School Monash University Melbourne Victoria AustraliaDepartment of Neurology New York University Grossman School of Medicine New York New York USADepartment of Medicine, Austin Health The University of Melbourne Heidelberg Victoria AustraliaDepartment of Medicine St. Vincent's Hospital, The University of Melbourne Fitzroy Victoria AustraliaDepartment of Neuroscience, Central Clinical School Monash University Melbourne Victoria AustraliaDepartment of Neurology New York University Grossman School of Medicine New York New York USADepartment of Neuroscience, Central Clinical School Monash University Melbourne Victoria AustraliaAbstract Objective In vitro data prompted U.S Food and Drug Administration warnings that lamotrigine, a common sodium channel modulating anti‐seizure medication (NaM‐ASM), could increase the risk of sudden death in patients with structural or ischaemic cardiac disease, however, its implications for Sudden Unexpected Death in Epilepsy (SUDEP) are unclear. Methods This retrospective, nested case–control study identified 101 sudden unexpected death in epilepsy (SUDEP) cases and 199 living epilepsy controls from Epilepsy Monitoring Units (EMUs) in Australia and the USA. Differences in proportions of lamotrigine and NaM‐ASM use were compared between cases and controls at the time of admission, and survival analyses from the time of admission up to 16 years were conducted. Multivariable logistic regression and survival analyses compared each ASM subgroup adjusting for SUDEP risk factors. Results Proportions of cases and controls prescribed lamotrigine (P = 0.166), one NaM‐ASM (P = 0.80), or ≥2NaM‐ASMs (P = 0.447) at EMU admission were not significantly different. Patients taking lamotrigine (adjusted hazard ratio [aHR] = 0.56; P = 0.054), one NaM‐ASM (aHR = 0.8; P = 0.588) or ≥2 NaM‐ASMs (aHR = 0.49; P = 0.139) at EMU admission were not at increased SUDEP risk up to 16 years following admission. Active tonic–clonic seizures at EMU admission associated with >2‐fold SUDEP risk, irrespective of lamotrigine (aHR = 2.24; P = 0.031) or NaM‐ASM use (aHR = 2.25; P = 0.029). Sensitivity analyses accounting for incomplete ASM data at follow‐up suggest undetected changes to ASM use are unlikely to alter our results. Significance This study provides additional evidence that lamotrigine and other NaM‐ASMs are unlikely to be associated with an increased long‐term risk of SUDEP, up to 16 years post‐EMU admission.https://doi.org/10.1002/epi4.12693 |
| spellingShingle | Russell Nightscales Sarah Barnard Juliana Laze Zhibin Chen Gerard Tao Clarissa Auvrez Shobi Sivathamboo Mark J. Cook Patrick Kwan Daniel Friedman Samuel F. Berkovic Wendyl D'Souza Piero Perucca Orrin Devinsky Terence J. O'Brien Risk of sudden unexpected death in epilepsy (SUDEP) with lamotrigine and other sodium channel‐modulating antiseizure medications Epilepsia Open |
| title | Risk of sudden unexpected death in epilepsy (SUDEP) with lamotrigine and other sodium channel‐modulating antiseizure medications |
| title_full | Risk of sudden unexpected death in epilepsy (SUDEP) with lamotrigine and other sodium channel‐modulating antiseizure medications |
| title_fullStr | Risk of sudden unexpected death in epilepsy (SUDEP) with lamotrigine and other sodium channel‐modulating antiseizure medications |
| title_full_unstemmed | Risk of sudden unexpected death in epilepsy (SUDEP) with lamotrigine and other sodium channel‐modulating antiseizure medications |
| title_short | Risk of sudden unexpected death in epilepsy (SUDEP) with lamotrigine and other sodium channel‐modulating antiseizure medications |
| title_sort | risk of sudden unexpected death in epilepsy sudep with lamotrigine and other sodium channel modulating antiseizure medications |
| url | https://doi.org/10.1002/epi4.12693 |
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