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March 10, 2020; 94 (10) Article

Antiepileptic drugs are not independently associated with cognitive dysfunction

Emma Foster, Charles B. Malpas, Karena Ye, Benjamin Johnstone, Patrick W. Carney, Dennis Velakoulis, Terence J. O'Brien, Patrick Kwan
First published February 3, 2020, DOI: https://doi.org/10.1212/WNL.0000000000009061
Emma Foster
From the Departments of Neurology (E.F., C.B.M., K.Y., B.J., T.J.O., P.K.) and Neuropsychiatry (D.V.), The Royal Melbourne Hospital, Parkville; Department of Neurology (E.F., C.B.M., T.J.O., P.K.), Alfred Health; Department of Neurosciences, Central Clinical School (E.F., T.J.O., P.K.), Monash University, Melbourne; Clinical Outcomes Research (CORe) Unit, Department of Medicine (RMH) (C.B.M.), The University of Melbourne, Parkville; Department of Medicine (P.W.C.), Monash University and Eastern Health; and Florey Institute of Neuroscience and Mental Health (P.W.C.), Melbourne, Australia.
FRACP
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Charles B. Malpas
From the Departments of Neurology (E.F., C.B.M., K.Y., B.J., T.J.O., P.K.) and Neuropsychiatry (D.V.), The Royal Melbourne Hospital, Parkville; Department of Neurology (E.F., C.B.M., T.J.O., P.K.), Alfred Health; Department of Neurosciences, Central Clinical School (E.F., T.J.O., P.K.), Monash University, Melbourne; Clinical Outcomes Research (CORe) Unit, Department of Medicine (RMH) (C.B.M.), The University of Melbourne, Parkville; Department of Medicine (P.W.C.), Monash University and Eastern Health; and Florey Institute of Neuroscience and Mental Health (P.W.C.), Melbourne, Australia.
PhD, MAPS, FCCN
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Karena Ye
From the Departments of Neurology (E.F., C.B.M., K.Y., B.J., T.J.O., P.K.) and Neuropsychiatry (D.V.), The Royal Melbourne Hospital, Parkville; Department of Neurology (E.F., C.B.M., T.J.O., P.K.), Alfred Health; Department of Neurosciences, Central Clinical School (E.F., T.J.O., P.K.), Monash University, Melbourne; Clinical Outcomes Research (CORe) Unit, Department of Medicine (RMH) (C.B.M.), The University of Melbourne, Parkville; Department of Medicine (P.W.C.), Monash University and Eastern Health; and Florey Institute of Neuroscience and Mental Health (P.W.C.), Melbourne, Australia.
MBBS
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Benjamin Johnstone
From the Departments of Neurology (E.F., C.B.M., K.Y., B.J., T.J.O., P.K.) and Neuropsychiatry (D.V.), The Royal Melbourne Hospital, Parkville; Department of Neurology (E.F., C.B.M., T.J.O., P.K.), Alfred Health; Department of Neurosciences, Central Clinical School (E.F., T.J.O., P.K.), Monash University, Melbourne; Clinical Outcomes Research (CORe) Unit, Department of Medicine (RMH) (C.B.M.), The University of Melbourne, Parkville; Department of Medicine (P.W.C.), Monash University and Eastern Health; and Florey Institute of Neuroscience and Mental Health (P.W.C.), Melbourne, Australia.
MD
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Patrick W. Carney
From the Departments of Neurology (E.F., C.B.M., K.Y., B.J., T.J.O., P.K.) and Neuropsychiatry (D.V.), The Royal Melbourne Hospital, Parkville; Department of Neurology (E.F., C.B.M., T.J.O., P.K.), Alfred Health; Department of Neurosciences, Central Clinical School (E.F., T.J.O., P.K.), Monash University, Melbourne; Clinical Outcomes Research (CORe) Unit, Department of Medicine (RMH) (C.B.M.), The University of Melbourne, Parkville; Department of Medicine (P.W.C.), Monash University and Eastern Health; and Florey Institute of Neuroscience and Mental Health (P.W.C.), Melbourne, Australia.
FRACP, PhD
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Dennis Velakoulis
From the Departments of Neurology (E.F., C.B.M., K.Y., B.J., T.J.O., P.K.) and Neuropsychiatry (D.V.), The Royal Melbourne Hospital, Parkville; Department of Neurology (E.F., C.B.M., T.J.O., P.K.), Alfred Health; Department of Neurosciences, Central Clinical School (E.F., T.J.O., P.K.), Monash University, Melbourne; Clinical Outcomes Research (CORe) Unit, Department of Medicine (RMH) (C.B.M.), The University of Melbourne, Parkville; Department of Medicine (P.W.C.), Monash University and Eastern Health; and Florey Institute of Neuroscience and Mental Health (P.W.C.), Melbourne, Australia.
DMedSc, FRANZCP
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Terence J. O'Brien
From the Departments of Neurology (E.F., C.B.M., K.Y., B.J., T.J.O., P.K.) and Neuropsychiatry (D.V.), The Royal Melbourne Hospital, Parkville; Department of Neurology (E.F., C.B.M., T.J.O., P.K.), Alfred Health; Department of Neurosciences, Central Clinical School (E.F., T.J.O., P.K.), Monash University, Melbourne; Clinical Outcomes Research (CORe) Unit, Department of Medicine (RMH) (C.B.M.), The University of Melbourne, Parkville; Department of Medicine (P.W.C.), Monash University and Eastern Health; and Florey Institute of Neuroscience and Mental Health (P.W.C.), Melbourne, Australia.
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Patrick Kwan
From the Departments of Neurology (E.F., C.B.M., K.Y., B.J., T.J.O., P.K.) and Neuropsychiatry (D.V.), The Royal Melbourne Hospital, Parkville; Department of Neurology (E.F., C.B.M., T.J.O., P.K.), Alfred Health; Department of Neurosciences, Central Clinical School (E.F., T.J.O., P.K.), Monash University, Melbourne; Clinical Outcomes Research (CORe) Unit, Department of Medicine (RMH) (C.B.M.), The University of Melbourne, Parkville; Department of Medicine (P.W.C.), Monash University and Eastern Health; and Florey Institute of Neuroscience and Mental Health (P.W.C.), Melbourne, Australia.
PhD, FRACP
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Antiepileptic drugs are not independently associated with cognitive dysfunction
Emma Foster, Charles B. Malpas, Karena Ye, Benjamin Johnstone, Patrick W. Carney, Dennis Velakoulis, Terence J. O'Brien, Patrick Kwan
Neurology Mar 2020, 94 (10) e1051-e1061; DOI: 10.1212/WNL.0000000000009061

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Abstract

Objective To test the hypothesis that individual antiepileptic drugs (AEDs) are not associated with cognitive impairment beyond other clinically relevant factors, we performed a cross-sectional study of patients admitted to an inpatient video-EEG monitoring unit.

Methods We prospectively enrolled patients admitted to an inpatient specialist epilepsy program between 2009 and 2016. Assessments included objective cognitive function, quality of life subscales for subjective cognitive function, and questionnaires for anxiety and depressive symptoms. Bayesian model averaging identified predictors of cognitive function. Bayesian model selection approach investigated effect of individual AEDs on cognition. Conventional frequentist analyses were also performed.

Results A total of 331 patients met inclusion criteria. Mean age was 39.3 years and 61.9% of patients were women. A total of 45.0% of patients were prescribed AED polypharmacy, 25.1% AED monotherapy, and 29.9% no AED. Age, seizure frequency, and a diagnosis of concomitant epilepsy and psychogenic nonepileptic seizure were predictors of objective cognitive function. Depression, anxiety, and seizure frequency were predictors of subjective cognitive function. Individual AEDs were not independently associated with impaired cognitive function beyond other clinically relevant variables.

Conclusions This study found that no AED was independently associated with cognitive dysfunction. Significant determinants of objective and subjective cognitive dysfunction included seizure frequency and depression, respectively. These findings suggest that optimizing therapy to prevent seizures is not likely to occur at the expense of cognitive function.

Glossary

AED=
antiepileptic drug;
BF=
Bayes factor;
BMA=
Bayesian model averaging;
GLM=
general linear model;
HADS=
Hospital Anxiety and Depression Scale;
NUCOG=
Neuropsychiatry Unit Cognitive Assessment Tool;
PCA=
principal components analysis;
PIP=
posterior inclusion probability;
PNES=
psychogenic nonepileptic seizures;
QOLIE=
Quality of Life in Epilepsy inventory;
VEM=
video-EEG monitoring

Footnotes

  • 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.

  • ↵* These authors contributed equally to this work.

  • Editorial, page 419

  • Podcast: NPub.org/neicin

  • CME Course: NPub.org/cmelist

  • Received May 1, 2019.
  • Accepted in final form October 10, 2019.
  • © 2020 American Academy of Neurology
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Letters: Rapid online correspondence

  • Author response: Antiepileptic drugs are not independently associated with cognitive dysfunction
    • Emma Foster, Neurologist, Alfred Health
    Submitted February 19, 2020
  • Reader response: Antiepileptic drugs are not independently associated with cognitive dysfunction
    • Juri-Alexander Witt, Neuropsychologist, Department of Epileptology, University Hospital Bonn (UKB)
    • Carolin Meschede, Neuropsychologist, Department of Epileptology, University Hospital Bonn (UKB)
    • Christoph Helmstaedter, Neuropsychologist, Department of Epileptology, University Hospital Bonn (UKB)
    Submitted February 12, 2020
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