Does the accumulated antiepileptic drug load in chronic epilepsy reflect disease severity?
antiepileptic drugs
disease severity
drug load
epilepsy
pharmacotherapy
Journal
Epilepsia
ISSN: 1528-1167
Titre abrégé: Epilepsia
Pays: United States
ID NLM: 2983306R
Informations de publication
Date de publication:
12 2020
12 2020
Historique:
received:
25
05
2020
revised:
18
09
2020
accepted:
18
09
2020
pubmed:
16
10
2020
medline:
4
3
2021
entrez:
15
10
2020
Statut:
ppublish
Résumé
To ascertain factors that are related to the antiepileptic drug load in epilepsy. In this cross-sectional study, we analyzed a large cohort of conservatively treated patients with epilepsy (n = 1135) and a smaller homogeneous group of presurgical patients with neuropathologically confirmed unilateral hippocampal sclerosis (n = 91). Considered clinical variables comprised (1) presence of an underlying cerebral lesion, (2) onset and (3) duration of epilepsy, (4) seizure frequency, (5) generalized or focal to bilateral tonic-clonic seizures, (6) ictal impairment of awareness, and (7) a history of convulsive status epilepticus. In the presurgical sample, we additionally considered (8) the degree of pathology (hippocampal neuronal cell densities) instead of (1) presence of a cerebral lesion and (9) an overall rating of epilepsy severity (GASE scale). Drug load was quantified as (a) the number of concomitant antiepileptic drugs (AEDs) and (b) the total defined daily dose (DDD). Analyses disclosed only small correlations between clinical variables and drug load indices. In the conservatively treated cohort, the multiple regression analyses revealed that epilepsy onset, cerebral lesion, history of convulsive status epilepticus, and seizure frequency combined explained only 6%-10% of variance in drug load. Nearly the same variance (5%-8%) could be explained by duration of epilepsy alone. Degree of hippocampal pathology and the epilepsy severity ratings were not related to drug load indices. Clinical markers of epilepsy severity were only marginally associated with drug load. Findings rather indicate that patients seem to accumulate drugs due to the chronicity of epilepsy. Overall, the drug load remained largely unexplained. The findings nevertheless call for scrutinizing multidrug therapies in patients with long-lasting epilepsies.
Substances chimiques
Anticonvulsants
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2685-2695Subventions
Organisme : Open access funding enabled and organized by ProjektDEAL
Informations de copyright
© 2020 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.
Références
Witt J-A, Elger CE, Helmstaedter C. Adverse cognitive effects of antiepileptic pharmacotherapy: Each additional drug matters. Eur Neuropsychopharmacol. 2015;25(11).
Kwan P, Brodie MJ. Early identification of refractory epilepsy. N Engl J Med. 2000;342(5):314-9.
Nuwer MR, Cendes F. Referring people with medically refractory seizures to an epilepsy center. Neurol Clin Pract. 2016;6(4):291-2.
Callaghan B, Schlesinger M, Rodemer W, Pollard J, Hesdorffer D, Allen Hauser W, et al. Remission and relapse in a drug-resistant epilepsy population followed prospectively. Epilepsia. 2011;52(3):619-26.
Luciano AL, Shorvon SD. Results of treatment changes in patients with apparently drug-resistant chronic epilepsy. Ann Neurol. 2007;62(4):375-81.
Steinhoff BJ, Staack AM, Wisniewski I. Seizure control with antiepileptic drug therapy in 517 consecutive adult outpatients at the Kork Epilepsy Centre. Epileptic Disord. 2012;14(4):379-87.
Steinhoff BJ, Hamer H, Trinka E, Schulze-Bonhage A, Bien C, Mayer T, et al. A multicenter survey of clinical experiences with perampanel in real life in Germany and Austria. Epilepsy Res. 2014;108(5):986-8.
Beyenburg S, Stavem K, Schmidt D. Placebo-corrected efficacy of modern antiepileptic drugs for refractory epilepsy: systematic review and meta-analysis. Epilepsia. 2010;51(1):7-26.
Mula M, Trimble MR. Antiepileptic drug-induced cognitive adverse effects: potential mechanisms and contributing factors. CNS Drugs. 2009;23(2):121-37.
Andrew T, Milinis K, Baker G, Wieshmann U. Self reported adverse effects of mono and polytherapy for epilepsy. Seizure. 2012;21(8):610-3.
Witt JA, Elger CE, Helmstaedter C. Impaired verbal fluency under topiramate - evidence for synergistic negative effects of epilepsy, topiramate, and polytherapy. Eur J Neurol. 2013;20(1):130-7.
Fisher RS, Acevedo C, Arzimanoglou A, Bogacz A, Cross JH, Elger CE, et al. ILAE Official Report: a practical clinical definition of epilepsy. Epilepsia. 2014;55(4):475-82.
Sajobi TT, Jette N, Zhang Y, Patten SB, Fiest KM, Engbers JDT, et al. Determinants of disease severity in adults with epilepsy: Results from the Neurological Diseases and Depression Study. Epilepsy Behav. 2015;51:170-5.
Chan CJ, Zou G, Wiebe S, Speechley KN. Global assessment of the severity of epilepsy (GASE) Scale in children: validity, reliability, responsiveness. Epilepsia. 2015;56(12):1950-6.
Cohen J. Statistical power analysis for the behavioral sciences, 2nd ed. Hillsdale, NJ: Lawrence Erlbaum Associates; 1988.
Löscher W, Schmidt D. Experimental and clinical evidence for loss of effect (tolerance) during prolonged treatment with antiepileptic drugs. Epilepsia. 2006;47(8):1253-84.
Stephen LJ, Brodie MJ. Antiepileptic drug monotherapy versus polytherapy. Curr Opin Neurol. 2012;25(2):164-72.
Witt J-A, Helmstaedter C. How can we overcome neuropsychological adverse effects of antiepileptic drugs? Expert Opin Pharmacother. 2017;18(6):1-4.
Pirio Richardson S, Farias ST, Lima AR, Alsaadi TM. Improvement in seizure control and quality of life in medically refractory epilepsy patients converted from polypharmacy to monotherapy. Epilepsy Behav. 2004;5(3):343-7.
Dash D, Aggarwal V, Joshi R, Padma MV, Tripathi M. Effect of reduction of antiepileptic drugs in patients with drug-refractory epilepsy. Seizure. 2015;27:25-9.
Perucca E, Kwan P. Overtreatment in epilepsy: How it occurs and how it can be avoided. CNS Drugs. 2005;19(11):897-908.
Baulac M. Rational conversion from antiepileptic polytherapy to monotherapy. Epileptic Disord. 2003;5(3):125-32.
Boshuisen K, Van Schooneveld MMJ, Uiterwaal CSPM, Cross JH, Harrison S, Polster T, et al. Intelligence quotient improves after antiepileptic drug withdrawal following pediatric epilepsy surgery. Ann Neurol. 2015;78(1):104-14.
Helmstaedter C, Elger CE, Witt JA. The effect of quantitative and qualitative antiepileptic drug changes on cognitive recovery after epilepsy surgery. Seizure. 2016;36:63-9.
Phabphal K, Kanjanasatien J. Montreal cognitive assessment in cryptogenic epilepsy patients with normal mini-mental state examination scores. Epileptic Disord. 2011;13(4):375-81.
Speechley KN, Sang X, Levin S, Zou GY, Eliasziw M, Lou SM, et al. Assessing severity of epilepsy in children: Preliminary evidence of validity and reliability of a single-item scale. Epilepsy Behav. 2008;13(2):337-42.