Cargando…

A 5-Year Study of Antiseizure Medications (ASMs) Monitoring in Patients with Neuropsychiatric Disorders in an Italian Clinical Center

Despite receiving appropriate antiseizure medications (ASMs), a relevant percentage of neuropsychiatric patients do not benefit from this approach, and one reason is subtherapeutic ASMs plasma concentration (C(p)) due to improper drug adherence, interindividual pharmacokinetic differences, or metabo...

Descripción completa

Detalles Bibliográficos
Autores principales: Biso, Letizia, Carli, Marco, Kolachalam, Shivakumar, Monticelli, Giorgio, Calabrò, Pasquale Fabio, di Paolo, Antonello, Giorgi, Filippo Sean, Bocci, Guido, Scarselli, Marco
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10383891/
https://www.ncbi.nlm.nih.gov/pubmed/37513857
http://dx.doi.org/10.3390/ph16070945
_version_ 1785081022426120192
author Biso, Letizia
Carli, Marco
Kolachalam, Shivakumar
Monticelli, Giorgio
Calabrò, Pasquale Fabio
di Paolo, Antonello
Giorgi, Filippo Sean
Bocci, Guido
Scarselli, Marco
author_facet Biso, Letizia
Carli, Marco
Kolachalam, Shivakumar
Monticelli, Giorgio
Calabrò, Pasquale Fabio
di Paolo, Antonello
Giorgi, Filippo Sean
Bocci, Guido
Scarselli, Marco
author_sort Biso, Letizia
collection PubMed
description Despite receiving appropriate antiseizure medications (ASMs), a relevant percentage of neuropsychiatric patients do not benefit from this approach, and one reason is subtherapeutic ASMs plasma concentration (C(p)) due to improper drug adherence, interindividual pharmacokinetic differences, or metabolic interactions among different drugs. For these reasons, therapeutic drug monitoring (TDM) by measuring ASMs C(p) is an effective tool that improves pharmacological therapies in clinical practice. Based on these premises, in the present real-world study, we analyzed the C(p) of the most used ASMs in diverse medical conditions, which were assayed during the years 2018–2022 at the University Hospital of Pisa, including about 24,000 samples. This population was largely heterogeneous, and our database did not contain clinical information about the patients. The most used ASMs were Valproate (VPA: 54.5%) and Levetiracetam (LEV: 18.6%), followed by Oxcarbazepine (OxCBZ: 8.3%) and Carbamazepine (CBZ: 7.2%), whereas the associations LEV/VPA, Ethosuximide (ESM)/VPA, and CBZ/VPA were the most frequently proposed. In about 2/3 of assays, ASMs C(p) was in range, except for VPA, which was underdosed in almost half of the samples. Importantly, toxic levels of ASMs C(p) were found very rarely. For VPA, there was a decrease of mean C(p) across ages, from adolescents to older patients, while the C(p) of LEV, CBZ, OxCBZ, and Topiramate (TPM) showed a slight tendency to increase. When we compared females and males, we found that for VPA, the average age was higher for females, whereas women taking Lamotrigine (LTG) and OxCBZ were younger than men. Then, comparing ASMs used in neurologic and psychiatric disorders, based on the request form, it emerged that the mean C(p) of CBZ, OxCBZ, and LTG on samples collected in the Psychiatric Unit was lower compared to the Neurology and Child Neuropsychiatry Units. Finally, the ASMs subjected to multiple dosing starting from an initial subtherapeutic C(p) increased their level at different time points within a year, reaching the reference range for some of them. In conclusion, the present study suggests that TDM is widely applied to monitor ASMs C(p), finding many of them within the reference range, as a demonstration of its utility in clinical practice.
format Online
Article
Text
id pubmed-10383891
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-103838912023-07-30 A 5-Year Study of Antiseizure Medications (ASMs) Monitoring in Patients with Neuropsychiatric Disorders in an Italian Clinical Center Biso, Letizia Carli, Marco Kolachalam, Shivakumar Monticelli, Giorgio Calabrò, Pasquale Fabio di Paolo, Antonello Giorgi, Filippo Sean Bocci, Guido Scarselli, Marco Pharmaceuticals (Basel) Article Despite receiving appropriate antiseizure medications (ASMs), a relevant percentage of neuropsychiatric patients do not benefit from this approach, and one reason is subtherapeutic ASMs plasma concentration (C(p)) due to improper drug adherence, interindividual pharmacokinetic differences, or metabolic interactions among different drugs. For these reasons, therapeutic drug monitoring (TDM) by measuring ASMs C(p) is an effective tool that improves pharmacological therapies in clinical practice. Based on these premises, in the present real-world study, we analyzed the C(p) of the most used ASMs in diverse medical conditions, which were assayed during the years 2018–2022 at the University Hospital of Pisa, including about 24,000 samples. This population was largely heterogeneous, and our database did not contain clinical information about the patients. The most used ASMs were Valproate (VPA: 54.5%) and Levetiracetam (LEV: 18.6%), followed by Oxcarbazepine (OxCBZ: 8.3%) and Carbamazepine (CBZ: 7.2%), whereas the associations LEV/VPA, Ethosuximide (ESM)/VPA, and CBZ/VPA were the most frequently proposed. In about 2/3 of assays, ASMs C(p) was in range, except for VPA, which was underdosed in almost half of the samples. Importantly, toxic levels of ASMs C(p) were found very rarely. For VPA, there was a decrease of mean C(p) across ages, from adolescents to older patients, while the C(p) of LEV, CBZ, OxCBZ, and Topiramate (TPM) showed a slight tendency to increase. When we compared females and males, we found that for VPA, the average age was higher for females, whereas women taking Lamotrigine (LTG) and OxCBZ were younger than men. Then, comparing ASMs used in neurologic and psychiatric disorders, based on the request form, it emerged that the mean C(p) of CBZ, OxCBZ, and LTG on samples collected in the Psychiatric Unit was lower compared to the Neurology and Child Neuropsychiatry Units. Finally, the ASMs subjected to multiple dosing starting from an initial subtherapeutic C(p) increased their level at different time points within a year, reaching the reference range for some of them. In conclusion, the present study suggests that TDM is widely applied to monitor ASMs C(p), finding many of them within the reference range, as a demonstration of its utility in clinical practice. MDPI 2023-06-29 /pmc/articles/PMC10383891/ /pubmed/37513857 http://dx.doi.org/10.3390/ph16070945 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Biso, Letizia
Carli, Marco
Kolachalam, Shivakumar
Monticelli, Giorgio
Calabrò, Pasquale Fabio
di Paolo, Antonello
Giorgi, Filippo Sean
Bocci, Guido
Scarselli, Marco
A 5-Year Study of Antiseizure Medications (ASMs) Monitoring in Patients with Neuropsychiatric Disorders in an Italian Clinical Center
title A 5-Year Study of Antiseizure Medications (ASMs) Monitoring in Patients with Neuropsychiatric Disorders in an Italian Clinical Center
title_full A 5-Year Study of Antiseizure Medications (ASMs) Monitoring in Patients with Neuropsychiatric Disorders in an Italian Clinical Center
title_fullStr A 5-Year Study of Antiseizure Medications (ASMs) Monitoring in Patients with Neuropsychiatric Disorders in an Italian Clinical Center
title_full_unstemmed A 5-Year Study of Antiseizure Medications (ASMs) Monitoring in Patients with Neuropsychiatric Disorders in an Italian Clinical Center
title_short A 5-Year Study of Antiseizure Medications (ASMs) Monitoring in Patients with Neuropsychiatric Disorders in an Italian Clinical Center
title_sort 5-year study of antiseizure medications (asms) monitoring in patients with neuropsychiatric disorders in an italian clinical center
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10383891/
https://www.ncbi.nlm.nih.gov/pubmed/37513857
http://dx.doi.org/10.3390/ph16070945
work_keys_str_mv AT bisoletizia a5yearstudyofantiseizuremedicationsasmsmonitoringinpatientswithneuropsychiatricdisordersinanitalianclinicalcenter
AT carlimarco a5yearstudyofantiseizuremedicationsasmsmonitoringinpatientswithneuropsychiatricdisordersinanitalianclinicalcenter
AT kolachalamshivakumar a5yearstudyofantiseizuremedicationsasmsmonitoringinpatientswithneuropsychiatricdisordersinanitalianclinicalcenter
AT monticelligiorgio a5yearstudyofantiseizuremedicationsasmsmonitoringinpatientswithneuropsychiatricdisordersinanitalianclinicalcenter
AT calabropasqualefabio a5yearstudyofantiseizuremedicationsasmsmonitoringinpatientswithneuropsychiatricdisordersinanitalianclinicalcenter
AT dipaoloantonello a5yearstudyofantiseizuremedicationsasmsmonitoringinpatientswithneuropsychiatricdisordersinanitalianclinicalcenter
AT giorgifilipposean a5yearstudyofantiseizuremedicationsasmsmonitoringinpatientswithneuropsychiatricdisordersinanitalianclinicalcenter
AT bocciguido a5yearstudyofantiseizuremedicationsasmsmonitoringinpatientswithneuropsychiatricdisordersinanitalianclinicalcenter
AT scarsellimarco a5yearstudyofantiseizuremedicationsasmsmonitoringinpatientswithneuropsychiatricdisordersinanitalianclinicalcenter
AT bisoletizia 5yearstudyofantiseizuremedicationsasmsmonitoringinpatientswithneuropsychiatricdisordersinanitalianclinicalcenter
AT carlimarco 5yearstudyofantiseizuremedicationsasmsmonitoringinpatientswithneuropsychiatricdisordersinanitalianclinicalcenter
AT kolachalamshivakumar 5yearstudyofantiseizuremedicationsasmsmonitoringinpatientswithneuropsychiatricdisordersinanitalianclinicalcenter
AT monticelligiorgio 5yearstudyofantiseizuremedicationsasmsmonitoringinpatientswithneuropsychiatricdisordersinanitalianclinicalcenter
AT calabropasqualefabio 5yearstudyofantiseizuremedicationsasmsmonitoringinpatientswithneuropsychiatricdisordersinanitalianclinicalcenter
AT dipaoloantonello 5yearstudyofantiseizuremedicationsasmsmonitoringinpatientswithneuropsychiatricdisordersinanitalianclinicalcenter
AT giorgifilipposean 5yearstudyofantiseizuremedicationsasmsmonitoringinpatientswithneuropsychiatricdisordersinanitalianclinicalcenter
AT bocciguido 5yearstudyofantiseizuremedicationsasmsmonitoringinpatientswithneuropsychiatricdisordersinanitalianclinicalcenter
AT scarsellimarco 5yearstudyofantiseizuremedicationsasmsmonitoringinpatientswithneuropsychiatricdisordersinanitalianclinicalcenter