Assessing Pharmacokinetic Correlates of Escitalopram-Related Adverse Drug Reactions.
Journal
Therapeutic drug monitoring
ISSN: 1536-3694
Titre abrégé: Ther Drug Monit
Pays: United States
ID NLM: 7909660
Informations de publication
Date de publication:
01 Apr 2024
01 Apr 2024
Historique:
received:
25
07
2023
accepted:
08
10
2023
medline:
18
3
2024
pubmed:
20
2
2024
entrez:
20
2
2024
Statut:
ppublish
Résumé
To assess the pharmacokinetic correlates of reported adverse drug reactions (ADRs) under antidepressant treatment with escitalopram (ESC) using a large therapeutic drug monitoring database. A large naturalistic sample of inpatients and outpatients prescribed ESC was analyzed. ADRs were classified using the Udvalg for Kliniske Undersogelser side effect rating scale. We compared ESC-treated patients with (n = 35) and without ADRs (n = 273) using ESC plasma concentrations as the primary outcome. We also compared ADR rates in the 2 groups based on 2 cut-off ESC levels reflecting the recommended upper thresholds of the therapeutic reference range of 80 ng/mL, suggested by the consensus therapeutic drug monitoring guidelines, and 40 ng/mL, based on recent meta-analysis data. The effects of age, sex, smoking, daily ESC dose, plasma concentrations, and concentrations corrected for daily dose were included in a binary logistic regression model to predict ADRs. No differences in clinical, demographic, or pharmacokinetic parameters were observed between patients with and without ADRs ( P > 0.05). Patients with ESC-related ADRs were more frequently diagnosed with psychotic disorders than those without (25% vs. 7.1%, P = 0.004). None of the variables was associated with ADR risk. Overall, ADR rates were not significantly different in patients above versus below thresholds of ESC concentrations (ESC concentrations >40 [n = 59] vs. ≤40 ng/mL [n = 249] and >80 [n = 8] vs. ≤80 ng/mL [n = 300]; P = 0.56 and P = 1.0, respectively). No distinct pharmacokinetic patterns underlying ESC-associated ADRs were observed. Further studies with more specific assessments of ADRs in larger cohorts are required to better identify potential underlying patterns.
Sections du résumé
BACKGROUND
BACKGROUND
To assess the pharmacokinetic correlates of reported adverse drug reactions (ADRs) under antidepressant treatment with escitalopram (ESC) using a large therapeutic drug monitoring database.
METHODS
METHODS
A large naturalistic sample of inpatients and outpatients prescribed ESC was analyzed. ADRs were classified using the Udvalg for Kliniske Undersogelser side effect rating scale. We compared ESC-treated patients with (n = 35) and without ADRs (n = 273) using ESC plasma concentrations as the primary outcome. We also compared ADR rates in the 2 groups based on 2 cut-off ESC levels reflecting the recommended upper thresholds of the therapeutic reference range of 80 ng/mL, suggested by the consensus therapeutic drug monitoring guidelines, and 40 ng/mL, based on recent meta-analysis data. The effects of age, sex, smoking, daily ESC dose, plasma concentrations, and concentrations corrected for daily dose were included in a binary logistic regression model to predict ADRs.
RESULTS
RESULTS
No differences in clinical, demographic, or pharmacokinetic parameters were observed between patients with and without ADRs ( P > 0.05). Patients with ESC-related ADRs were more frequently diagnosed with psychotic disorders than those without (25% vs. 7.1%, P = 0.004). None of the variables was associated with ADR risk. Overall, ADR rates were not significantly different in patients above versus below thresholds of ESC concentrations (ESC concentrations >40 [n = 59] vs. ≤40 ng/mL [n = 249] and >80 [n = 8] vs. ≤80 ng/mL [n = 300]; P = 0.56 and P = 1.0, respectively).
CONCLUSIONS
CONCLUSIONS
No distinct pharmacokinetic patterns underlying ESC-associated ADRs were observed. Further studies with more specific assessments of ADRs in larger cohorts are required to better identify potential underlying patterns.
Identifiants
pubmed: 38377253
doi: 10.1097/FTD.0000000000001183
pii: 00007691-990000000-00191
pmc: PMC10930353
doi:
Substances chimiques
Escitalopram
4O4S742ANY
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
246-251Informations de copyright
Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association of Therapeutic Drug Monitoring and Clinical Toxicology.
Déclaration de conflit d'intérêts
M. Kuzin has received travel grants from Sunovion Pharmaceutical (Basel, Switzerland) and Otsuka Pharmaceutical (Glattbrugg, Switzerland). He also received a travel grant, participated, and obtained a grant at speaker board of Lundbeck (Zurich, Switzerland). M. Paulzen has received speaker fees from the following pharmaceutical companies: Neurax Pharm, Lundbeck, Janssen, Otsuka, Idorsia, and Rovi. He has served as a consultant for Neurax Pharm, Otsuka, Lundbeck, Idorsia, and Rovi. He is an editor of PSIAC, an Internet-based drug–drug interaction program for psychopharmacotherapy ( www.psiac.de ). He reports no conflict of interest with this publication. Dr. Schoretsanitis has served as a consultant for Dexcel Pharma, HLS Therapeutics, and Thermo Fisher and has received speaker fees from HLS Therapeutics. The authors declare no conflict of interest.
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