The Adverse Effects of Commonly Prescribed Antiseizure Medications in Adults With Newly Diagnosed Focal Epilepsy

Sarah N. Barnard, From the Department of Neuroscience (S.N.B., Z.C., P.P.), Central Clinical School, and Clinical Epidemiology (Z.C.), School of Public Health and Preventive Medicine, Monash University; Department of Neurology (S.N.B., Z.C., P.P.), Alfred Health, Melbourne, Australia; Department of Neurology (S.N.B., J.F.), New York University Grossman School of Medicine, New York; Department of Neurology (A.M.K.), University of Miami, Miller School of Medicine, FL; Department of Neurology (M.G.H.), Westchester Medical Center Health, Valhalla, NY; Mid-Atlantic Epilepsy and Sleep Center (P.K.), Bethesda, MD; Department of Neurology (P.K.), The George Washington University, DC; Department of Neurology (B.W.A.-K.), Vanderbilt University Medical Center, Nashville, TN; School of Pharmacy (B.E.G.), University of Wisconsin, Madison; Department of Neurology (P.P.), The Royal Melbourne Hospital; Department of Medicine (P.P.), Austin Health, The University of Melbourne; and Bladin-Berkovic Comprehensive Epilepsy Program (P.P.), Department of Neurology, Austin Health, Heidelberg, Australia.
Zhibin Chen, From the Department of Neuroscience (S.N.B., Z.C., P.P.), Central Clinical School, and Clinical Epidemiology (Z.C.), School of Public Health and Preventive Medicine, Monash University; Department of Neurology (S.N.B., Z.C., P.P.), Alfred Health, Melbourne, Australia; Department of Neurology (S.N.B., J.F.), New York University Grossman School of Medicine, New York; Department of Neurology (A.M.K.), University of Miami, Miller School of Medicine, FL; Department of Neurology (M.G.H.), Westchester Medical Center Health, Valhalla, NY; Mid-Atlantic Epilepsy and Sleep Center (P.K.), Bethesda, MD; Department of Neurology (P.K.), The George Washington University, DC; Department of Neurology (B.W.A.-K.), Vanderbilt University Medical Center, Nashville, TN; School of Pharmacy (B.E.G.), University of Wisconsin, Madison; Department of Neurology (P.P.), The Royal Melbourne Hospital; Department of Medicine (P.P.), Austin Health, The University of Melbourne; and Bladin-Berkovic Comprehensive Epilepsy Program (P.P.), Department of Neurology, Austin Health, Heidelberg, Australia.
Andres M. Kanner, From the Department of Neuroscience (S.N.B., Z.C., P.P.), Central Clinical School, and Clinical Epidemiology (Z.C.), School of Public Health and Preventive Medicine, Monash University; Department of Neurology (S.N.B., Z.C., P.P.), Alfred Health, Melbourne, Australia; Department of Neurology (S.N.B., J.F.), New York University Grossman School of Medicine, New York; Department of Neurology (A.M.K.), University of Miami, Miller School of Medicine, FL; Department of Neurology (M.G.H.), Westchester Medical Center Health, Valhalla, NY; Mid-Atlantic Epilepsy and Sleep Center (P.K.), Bethesda, MD; Department of Neurology (P.K.), The George Washington University, DC; Department of Neurology (B.W.A.-K.), Vanderbilt University Medical Center, Nashville, TN; School of Pharmacy (B.E.G.), University of Wisconsin, Madison; Department of Neurology (P.P.), The Royal Melbourne Hospital; Department of Medicine (P.P.), Austin Health, The University of Melbourne; and Bladin-Berkovic Comprehensive Epilepsy Program (P.P.), Department of Neurology, Austin Health, Heidelberg, Australia.
Manisha G. Holmes, From the Department of Neuroscience (S.N.B., Z.C., P.P.), Central Clinical School, and Clinical Epidemiology (Z.C.), School of Public Health and Preventive Medicine, Monash University; Department of Neurology (S.N.B., Z.C., P.P.), Alfred Health, Melbourne, Australia; Department of Neurology (S.N.B., J.F.), New York University Grossman School of Medicine, New York; Department of Neurology (A.M.K.), University of Miami, Miller School of Medicine, FL; Department of Neurology (M.G.H.), Westchester Medical Center Health, Valhalla, NY; Mid-Atlantic Epilepsy and Sleep Center (P.K.), Bethesda, MD; Department of Neurology (P.K.), The George Washington University, DC; Department of Neurology (B.W.A.-K.), Vanderbilt University Medical Center, Nashville, TN; School of Pharmacy (B.E.G.), University of Wisconsin, Madison; Department of Neurology (P.P.), The Royal Melbourne Hospital; Department of Medicine (P.P.), Austin Health, The University of Melbourne; and Bladin-Berkovic Comprehensive Epilepsy Program (P.P.), Department of Neurology, Austin Health, Heidelberg, Australia.
Pavel Klein, From the Department of Neuroscience (S.N.B., Z.C., P.P.), Central Clinical School, and Clinical Epidemiology (Z.C.), School of Public Health and Preventive Medicine, Monash University; Department of Neurology (S.N.B., Z.C., P.P.), Alfred Health, Melbourne, Australia; Department of Neurology (S.N.B., J.F.), New York University Grossman School of Medicine, New York; Department of Neurology (A.M.K.), University of Miami, Miller School of Medicine, FL; Department of Neurology (M.G.H.), Westchester Medical Center Health, Valhalla, NY; Mid-Atlantic Epilepsy and Sleep Center (P.K.), Bethesda, MD; Department of Neurology (P.K.), The George Washington University, DC; Department of Neurology (B.W.A.-K.), Vanderbilt University Medical Center, Nashville, TN; School of Pharmacy (B.E.G.), University of Wisconsin, Madison; Department of Neurology (P.P.), The Royal Melbourne Hospital; Department of Medicine (P.P.), Austin Health, The University of Melbourne; and Bladin-Berkovic Comprehensive Epilepsy Program (P.P.), Department of Neurology, Austin Health, Heidelberg, Australia.
Bassel W. Abou-Khalil, From the Department of Neuroscience (S.N.B., Z.C., P.P.), Central Clinical School, and Clinical Epidemiology (Z.C.), School of Public Health and Preventive Medicine, Monash University; Department of Neurology (S.N.B., Z.C., P.P.), Alfred Health, Melbourne, Australia; Department of Neurology (S.N.B., J.F.), New York University Grossman School of Medicine, New York; Department of Neurology (A.M.K.), University of Miami, Miller School of Medicine, FL; Department of Neurology (M.G.H.), Westchester Medical Center Health, Valhalla, NY; Mid-Atlantic Epilepsy and Sleep Center (P.K.), Bethesda, MD; Department of Neurology (P.K.), The George Washington University, DC; Department of Neurology (B.W.A.-K.), Vanderbilt University Medical Center, Nashville, TN; School of Pharmacy (B.E.G.), University of Wisconsin, Madison; Department of Neurology (P.P.), The Royal Melbourne Hospital; Department of Medicine (P.P.), Austin Health, The University of Melbourne; and Bladin-Berkovic Comprehensive Epilepsy Program (P.P.), Department of Neurology, Austin Health, Heidelberg, Australia.
Barry E. Gidal, From the Department of Neuroscience (S.N.B., Z.C., P.P.), Central Clinical School, and Clinical Epidemiology (Z.C.), School of Public Health and Preventive Medicine, Monash University; Department of Neurology (S.N.B., Z.C., P.P.), Alfred Health, Melbourne, Australia; Department of Neurology (S.N.B., J.F.), New York University Grossman School of Medicine, New York; Department of Neurology (A.M.K.), University of Miami, Miller School of Medicine, FL; Department of Neurology (M.G.H.), Westchester Medical Center Health, Valhalla, NY; Mid-Atlantic Epilepsy and Sleep Center (P.K.), Bethesda, MD; Department of Neurology (P.K.), The George Washington University, DC; Department of Neurology (B.W.A.-K.), Vanderbilt University Medical Center, Nashville, TN; School of Pharmacy (B.E.G.), University of Wisconsin, Madison; Department of Neurology (P.P.), The Royal Melbourne Hospital; Department of Medicine (P.P.), Austin Health, The University of Melbourne; and Bladin-Berkovic Comprehensive Epilepsy Program (P.P.), Department of Neurology, Austin Health, Heidelberg, Australia.
Jacqueline French, From the Department of Neuroscience (S.N.B., Z.C., P.P.), Central Clinical School, and Clinical Epidemiology (Z.C.), School of Public Health and Preventive Medicine, Monash University; Department of Neurology (S.N.B., Z.C., P.P.), Alfred Health, Melbourne, Australia; Department of Neurology (S.N.B., J.F.), New York University Grossman School of Medicine, New York; Department of Neurology (A.M.K.), University of Miami, Miller School of Medicine, FL; Department of Neurology (M.G.H.), Westchester Medical Center Health, Valhalla, NY; Mid-Atlantic Epilepsy and Sleep Center (P.K.), Bethesda, MD; Department of Neurology (P.K.), The George Washington University, DC; Department of Neurology (B.W.A.-K.), Vanderbilt University Medical Center, Nashville, TN; School of Pharmacy (B.E.G.), University of Wisconsin, Madison; Department of Neurology (P.P.), The Royal Melbourne Hospital; Department of Medicine (P.P.), Austin Health, The University of Melbourne; and Bladin-Berkovic Comprehensive Epilepsy Program (P.P.), Department of Neurology, Austin Health, Heidelberg, Australia.
Piero Perucca, From the Department of Neuroscience (S.N.B., Z.C., P.P.), Central Clinical School, and Clinical Epidemiology (Z.C.), School of Public Health and Preventive Medicine, Monash University; Department of Neurology (S.N.B., Z.C., P.P.), Alfred Health, Melbourne, Australia; Department of Neurology (S.N.B., J.F.), New York University Grossman School of Medicine, New York; Department of Neurology (A.M.K.), University of Miami, Miller School of Medicine, FL; Department of Neurology (M.G.H.), Westchester Medical Center Health, Valhalla, NY; Mid-Atlantic Epilepsy and Sleep Center (P.K.), Bethesda, MD; Department of Neurology (P.K.), The George Washington University, DC; Department of Neurology (B.W.A.-K.), Vanderbilt University Medical Center, Nashville, TN; School of Pharmacy (B.E.G.), University of Wisconsin, Madison; Department of Neurology (P.P.), The Royal Melbourne Hospital; Department of Medicine (P.P.), Austin Health, The University of Melbourne; and Bladin-Berkovic Comprehensive Epilepsy Program (P.P.), Department of Neurology, Austin Health, Heidelberg, Australia.

Document Type

Journal Article

Publication Date

10-8-2024

Journal

Neurology

Volume

103

Issue

7

DOI

10.1212/WNL.0000000000209821

Abstract

BACKGROUND AND OBJECTIVES: Systematic screening can help identify antiseizure medication (ASM)-associated adverse events (AEs) that may preclude patients from reaching effective doses or completing adequate trial periods. The Adverse Event Profile (AEP) is a self-completed instrument to identify the frequency of common AEs associated with ASM use. This study aimed to compare the AE profile of commonly used ASMs in adults with newly diagnosed focal epilepsy. METHODS: The Human Epilepsy Project is a prospective, international, observational study investigating markers of treatment response in newly diagnosed focal epilepsy. Participants were enrolled within 4 months of treatment initiation. Adult participants on levetiracetam, lamotrigine, carbamazepine, or oxcarbazepine monotherapy who completed the AEP and Mini International Neuropsychiatric Interview at enrollment were included. Multivariable generalized linear and penalized logistic regression models assessed differences in total and itemized marginal AEP scores and dichotomized responses ("never/rarely" vs "sometimes/always"). RESULTS: A total of 225 adults initiated on levetiracetam (n = 132, 59%), lamotrigine (n = 55, 24%), carbamazepine (n = 19, 8.4%), or oxcarbazepine (n = 19, 8.4%) were included. There were no significant differences in AEP total scores between ASMs. Patients with depression (adjusted marginal score ratio [aMSR] 1.23, 95% CI 1.09-1.39, p = 0.001) and anxiety (aMSR 1.15, 95% CI 1.04-1.26, p = 0.007) had worse AEP total scores than those without. After adjusting for depression and anxiety, levetiracetam users were >3 times more likely to report feelings of aggression (adjusted odds ratio [aOR] 3.38, 95% CI 1.07-10.7, p = 0.038) and almost half as likely to experience unsteadiness (aOR 0.45, 95% CI 0.21-0.99, p = 0.047) than lamotrigine users. Carbamazepine and oxcarbazepine had the highest rates of discontinuation (42.1%, each), followed by levetiracetam (34.8%) and lamotrigine (16.4%). Levetiracetam users had the highest proportion of discontinuations because of AEs alone (18%), and lamotrigine had the lowest (5%). DISCUSSION: Systematic screening for AEs in adults with newly diagnosed focal epilepsy on ASM monotherapy showed that those with comorbid psychiatric conditions report greater AEs overall, irrespective of ASM. Levetiracetam was associated with >3-fold risk of psychiatric AEs and half the risk of experiencing unsteadiness than lamotrigine. Levetiracetam had the highest proportion of discontinuations because of AEs alone, while lamotrigine had the lowest.

Department

Neurology

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