Severity of Topiramate-Related Working Memory Impairment Is Modulated by Plasma Concentration and Working Memory Capacity.
Adolescent
Adult
Anticonvulsants
/ administration & dosage
Cognition
/ drug effects
Cognitive Dysfunction
/ blood
Cross-Over Studies
Dose-Response Relationship, Drug
Double-Blind Method
Female
Healthy Volunteers
Humans
Male
Memory, Short-Term
/ drug effects
Models, Biological
Neuropsychological Tests
Topiramate
/ administration & dosage
Young Adult
cognitive impairment
modeling
pharmacokinetic/pharmacodynamic
topiramate
working memory
Journal
Journal of clinical pharmacology
ISSN: 1552-4604
Titre abrégé: J Clin Pharmacol
Pays: England
ID NLM: 0366372
Informations de publication
Date de publication:
09 2020
09 2020
Historique:
received:
16
09
2019
accepted:
25
02
2020
pubmed:
17
4
2020
medline:
1
7
2021
entrez:
17
4
2020
Statut:
ppublish
Résumé
Drug side effects that impair cognition can lead to diminished quality of life and discontinuation of therapy. Topiramate is an antiepileptic drug that elicits cognitive deficits more frequently than other antiepileptic drugs, impairing multiple cognitive domains including language, attention, and memory. Although up to 40% of individuals taking topiramate may experience cognitive deficits, we are currently unable to predict which individuals will be most severely affected before administration. The objective of this study was to show the contributions of plasma concentration and working memory capacity in determining the severity of an individual's topiramate-related cognitive impairment. Subjects were enrolled in a double-blind, placebo-controlled crossover study during which they received a single dose of either 100, 150, or 200 mg topiramate. Working memory function was assessed using a modified Sternberg working memory task with 3 memory loads administered 4 hours after dosing. After adjustment for differences in working memory capacity, each 1 μg/mL of topiramate plasma concentration was associated with a 3.6% decrease in accuracy for all memory loads. Placebo effects occurred as a function of working memory capacity, with individuals with high working memory capacity experiencing less severe placebo-related impairment compared with those with low working memory capacity. Our results demonstrate that severity of topiramate-related cognitive deficits occurs as a function of both drug exposure and baseline cognitive function. By identifying patient- and exposure-related characteristics that modulate the severity of cognitive side effects, topiramate dosing strategies may be individually tailored in the future to prevent unwanted cognitive impairment.
Identifiants
pubmed: 32297992
doi: 10.1002/jcph.1611
pmc: PMC7572737
mid: NIHMS1574218
doi:
Substances chimiques
Anticonvulsants
0
Topiramate
0H73WJJ391
Banques de données
ClinicalTrials.gov
['NCT01889602']
Types de publication
Journal Article
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1166-1176Subventions
Organisme : NINDS NIH HHS
ID : R01 NS076665
Pays : United States
Organisme : NINDS NIH HHS
ID : P50 NS016308
Pays : United States
Informations de copyright
© 2020, The American College of Clinical Pharmacology.
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