Adverse events related to antiepileptic drugs

Yew Li Dang; Emma Foster; Michael Lloyd; Genevieve Rayner; Maria Rychkova; Rashida Ali; Patrick W Carney; Dennis Velakoulis; Toby T Winton-Brown; Tomas Kalincik; Piero Perucca; Terence J O'Brien; Patrick Kwan; Charles B Malpas

doi:10.1016/j.yebeh.2020.107657

Adverse events related to antiepileptic drugs

Epilepsy Behav. 2021 Feb:115:107657. doi: 10.1016/j.yebeh.2020.107657. Epub 2020 Dec 22.

Authors

Affiliations

¹ Department of Neurology, The Royal Melbourne Hospital, Parkville, Australia.
² Department of Neurology, The Royal Melbourne Hospital, Parkville, Australia; Department of Neurology, Alfred Health, Melbourne, Australia; Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Australia. Electronic address: emma.foster@monash.edu.
³ Department of Psychiatry, Alfred Health, Melbourne, Australia.
⁴ Melbourne School of Psychological Sciences, University of Melbourne, Parkville, Australia.
⁵ Department of Neurology, The Royal Melbourne Hospital, Parkville, Australia; Department of Neurology, Alfred Health, Melbourne, Australia; Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Parkville, Australia.
⁶ Department of Neurology, Alfred Health, Melbourne, Australia; Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Australia.
⁷ Department of Medicine, Monash University and Eastern Health, Melbourne, Australia; Florey Institute of Neuroscience and Mental Health, Melbourne, Australia.
⁸ Department of Neuropsychiatry, The Royal Melbourne Hospital, Parkville, Australia.
⁹ Department of Neurology, The Royal Melbourne Hospital, Parkville, Australia; Clinical Outcomes Research (CORe) Unit, Department of Medicine (RMH), The University of Melbourne, Parkville, Australia.
¹⁰ Department of Neurology, The Royal Melbourne Hospital, Parkville, Australia; Department of Neurology, Alfred Health, Melbourne, Australia; Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Australia; Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Parkville, Australia.
¹¹ Department of Neurology, The Royal Melbourne Hospital, Parkville, Australia; Department of Neurology, Alfred Health, Melbourne, Australia; Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Parkville, Australia; Clinical Outcomes Research (CORe) Unit, Department of Medicine (RMH), The University of Melbourne, Parkville, Australia.

PMID: 33360400
DOI: 10.1016/j.yebeh.2020.107657

Abstract

Objective: Adverse events (AEs) related to antiepileptic drugs (AEDs) may interfere with adequate dosing and patient adherence, leading to suboptimal seizure control, and relatedly, increased injuries, hospitalizations, and mortality. This study investigated the clinicodemographic factors associated with AEs related to AEDs as reported by the Liverpool Adverse Events Profile (LAEP), and explored the ability of LAEP to discriminate between epilepsy and psychogenic nonepileptic seizures (PNES). We hypothesized that female sex, mood disorders, AED-polytherapy, duration, and severity of epilepsy are associated with increased endorsement of AEs related to AEDs, and that endorsement of AEs related to AEDs would significantly differ between epilepsy and PNES patients.

Methods: We prospectively enrolled adult patients admitted to two inpatient video-electroencephalogram monitoring units. Clinicodemographic variables and psychometric measures of depression, anxiety, and cognitive function were recorded. Patient-reported AE endorsement was obtained using the LAEP, which was reduced to four latent domains using exploratory structural equation modeling. General linear models identified variables associated with each domain. Logistic regression determined the ability of LAEP scores to differentiate between epilepsy and PNES.

Results: 311 patients met inclusion criteria. Mean age was 38 years and 56% of patients were female. Network analysis demonstrated strong relationships between depression and anxiety with physical, sleep, psychiatric, and dermatological AE endorsement. Depression, female sex, and AED polytherapy were associated with greater AE endorsement. Epilepsy, compared to PNES, was associated with lower AE endorsement. Fewer prescribed AEDs and greater reported physical AE endorsement were associated with PNES diagnosis.

Significance: There is a strong relationship between patient-reported AEs and psychiatric symptomatology. Those with PNES paradoxically endorse greater physical AEs despite receiving fewer AEDs. Patients who endorse AEs in clinical practice should be screened for comorbid depression or anxiety and treated accordingly.

Keywords: Adverse event; All epilepsy/seizures; Antiepileptic drugs; Depression; Video/EEG use in epilepsy.

MeSH terms

Adult
Anticonvulsants* / adverse effects
Anxiety / chemically induced
Anxiety Disorders / drug therapy
Electroencephalography
Epilepsy* / drug therapy
Female
Humans
Seizures / chemically induced
Seizures / drug therapy

Substances

Anticonvulsants