Pharmacodynamic interactions of antiepileptic drugs: From bench to clinical practice.
Animals
Anticonvulsants
/ administration & dosage
Drug Evaluation, Preclinical
/ methods
Drug Interactions
/ physiology
Drug Therapy, Combination
Epilepsy
/ drug therapy
Humans
Lacosamide
/ administration & dosage
Lamotrigine
/ administration & dosage
Prospective Studies
Valproic Acid
/ administration & dosage
Antiepileptic drugs
Human studies
Pharmacodynamic interactions
Pharmacoresistant epilepsy
Polytherapy
Preclinical studies
Journal
Epilepsy & behavior : E&B
ISSN: 1525-5069
Titre abrégé: Epilepsy Behav
Pays: United States
ID NLM: 100892858
Informations de publication
Date de publication:
03 2020
03 2020
Historique:
received:
07
10
2019
revised:
15
01
2020
accepted:
17
01
2020
pubmed:
15
2
2020
medline:
15
12
2020
entrez:
15
2
2020
Statut:
ppublish
Résumé
Approximately 50% of patients do not achieve seizure control with antiepileptic drug (AED) monotherapy, and polytherapy, with more than one AED, is often required. To date, no evidence-based criteria on how to combine AEDs exist. This narrative review aimed to provide critical findings of the available literature about the role of pharmacodynamic AEDs' interactions in patients whose epilepsies were treated with polytherapy. Electronic databases, Medical Literature Analysis and Retrieval System Online (MEDLINE) and Excerpta Medica dataBASE (EMBASE), were systematically searched to identify relevant studies on pharmacodynamic AEDs' interactions in patients with epilepsy. Most data on AED combinations are coming from animal models and preclinical studies. Combining AEDs with different mechanisms of actions seems to have greater effectiveness and lower risk of adverse event development. Conversely, the combination of AEDs may cause pharmacodynamic synergistic effects that may result in not only increased efficacy but also more adverse effects. Despite some AED associations that have been proven to be effective in specific epilepsy/seizure type (e.g., phenobarbital+/phenytoin for tonic seizures and ethosiximide + valproate for absences; lamotrigine + valproate for various epilepsy/seizure types), no clear and definitive evidence exists about AED combinations in humans. Examples of pharmacodynamic interactions that possibly explain the synergistic effects on efficacy or adverse effects include the combination between vigabatrin or pregabalin and sodium channel blockers (supra-additive antiseizure effect) and lacosamide combined with other sodium channel blockers (infra-additive antiseizure effect and neurotoxicity synergistic). The pharmacodynamic lamotrigine-valproate interaction is also supported by synergistic adverse events. Therefore, well-designed double-blind prospective studies recruiting a sufficient number of patients possibly with a crossover design and carefully ascertain the role of pharmacokinetic interactions and variations of AEDs' levels in the blood are needed.
Sections du résumé
BACKGROUND
Approximately 50% of patients do not achieve seizure control with antiepileptic drug (AED) monotherapy, and polytherapy, with more than one AED, is often required. To date, no evidence-based criteria on how to combine AEDs exist.
OBJECTIVE
This narrative review aimed to provide critical findings of the available literature about the role of pharmacodynamic AEDs' interactions in patients whose epilepsies were treated with polytherapy.
METHODS
Electronic databases, Medical Literature Analysis and Retrieval System Online (MEDLINE) and Excerpta Medica dataBASE (EMBASE), were systematically searched to identify relevant studies on pharmacodynamic AEDs' interactions in patients with epilepsy.
RESULTS AND CONCLUSION
Most data on AED combinations are coming from animal models and preclinical studies. Combining AEDs with different mechanisms of actions seems to have greater effectiveness and lower risk of adverse event development. Conversely, the combination of AEDs may cause pharmacodynamic synergistic effects that may result in not only increased efficacy but also more adverse effects. Despite some AED associations that have been proven to be effective in specific epilepsy/seizure type (e.g., phenobarbital+/phenytoin for tonic seizures and ethosiximide + valproate for absences; lamotrigine + valproate for various epilepsy/seizure types), no clear and definitive evidence exists about AED combinations in humans. Examples of pharmacodynamic interactions that possibly explain the synergistic effects on efficacy or adverse effects include the combination between vigabatrin or pregabalin and sodium channel blockers (supra-additive antiseizure effect) and lacosamide combined with other sodium channel blockers (infra-additive antiseizure effect and neurotoxicity synergistic). The pharmacodynamic lamotrigine-valproate interaction is also supported by synergistic adverse events. Therefore, well-designed double-blind prospective studies recruiting a sufficient number of patients possibly with a crossover design and carefully ascertain the role of pharmacokinetic interactions and variations of AEDs' levels in the blood are needed.
Identifiants
pubmed: 32058303
pii: S1525-5050(19)31072-8
doi: 10.1016/j.yebeh.2020.106939
pii:
doi:
Substances chimiques
Anticonvulsants
0
Lacosamide
563KS2PQY5
Valproic Acid
614OI1Z5WI
Lamotrigine
U3H27498KS
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
106939Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors declare no conflicts of interest.