Cargando…

Individual and simultaneous treatment with antipsychotic aripiprazole and antidepressant trazodone inhibit sterol biosynthesis in the adult brain

Polypharmacy, or the simultaneous use of multiple drugs to treat a single patient, is a common practice in psychiatry. Unfortunately, data on the health effects of commonly used combinations of medications are very limited. In this study, we therefore investigated the effects and interactions betwee...

Descripción completa

Detalles Bibliográficos
Autores principales: Balog, Marta, Anderson, Allison, Genaro-Mattos, Thiago C., Korade, Zeljka, Mirnics, Karoly
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Biochemistry and Molecular Biology 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9386463/
https://www.ncbi.nlm.nih.gov/pubmed/35839864
http://dx.doi.org/10.1016/j.jlr.2022.100249
_version_ 1784769816730533888
author Balog, Marta
Anderson, Allison
Genaro-Mattos, Thiago C.
Korade, Zeljka
Mirnics, Karoly
author_facet Balog, Marta
Anderson, Allison
Genaro-Mattos, Thiago C.
Korade, Zeljka
Mirnics, Karoly
author_sort Balog, Marta
collection PubMed
description Polypharmacy, or the simultaneous use of multiple drugs to treat a single patient, is a common practice in psychiatry. Unfortunately, data on the health effects of commonly used combinations of medications are very limited. In this study, we therefore investigated the effects and interactions between two commonly prescribed psychotropic medications with sterol inhibiting side effects, trazodone (TRZ), an antidepressant, and aripiprazole (ARI), an antipsychotic. In vitro cell culture experiments revealed that both medications alone disrupted neuronal and astroglial sterol biosynthesis in dose-dependent manners. Furthermore, when ARI and TRZ were combined, exposure resulted in an additive 7-dehydrocholesterol (7-DHC) increase, as well as desmosterol (DES) and cholesterol decreases in both cell types. In adult mice, at baseline, we found that the three investigated sterols showed significant differences in distribution across the eight assessed brain regions. Furthermore, experimental mice treated with ARI or TRZ, or a combination of both medications for 8 days, showed strong sterol disruption across all brain regions. We show ARI or TRZ alone elevated 7-DHC and decreased DES levels in all brain regions, but with regional differences. However, the combined utilization of these two medications for 8 days did not lead to additive changes in sterol disturbances. Based on the complex roles of 7-DHC derived oxysterols, we conclude that individual and potentially simultaneous use of medications with sterol biosynthesis-inhibiting properties might have undesired side effects on the adult brain, with as yet unknown long-term consequences on mental or physical health.
format Online
Article
Text
id pubmed-9386463
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher American Society for Biochemistry and Molecular Biology
record_format MEDLINE/PubMed
spelling pubmed-93864632022-08-22 Individual and simultaneous treatment with antipsychotic aripiprazole and antidepressant trazodone inhibit sterol biosynthesis in the adult brain Balog, Marta Anderson, Allison Genaro-Mattos, Thiago C. Korade, Zeljka Mirnics, Karoly J Lipid Res Research Article Polypharmacy, or the simultaneous use of multiple drugs to treat a single patient, is a common practice in psychiatry. Unfortunately, data on the health effects of commonly used combinations of medications are very limited. In this study, we therefore investigated the effects and interactions between two commonly prescribed psychotropic medications with sterol inhibiting side effects, trazodone (TRZ), an antidepressant, and aripiprazole (ARI), an antipsychotic. In vitro cell culture experiments revealed that both medications alone disrupted neuronal and astroglial sterol biosynthesis in dose-dependent manners. Furthermore, when ARI and TRZ were combined, exposure resulted in an additive 7-dehydrocholesterol (7-DHC) increase, as well as desmosterol (DES) and cholesterol decreases in both cell types. In adult mice, at baseline, we found that the three investigated sterols showed significant differences in distribution across the eight assessed brain regions. Furthermore, experimental mice treated with ARI or TRZ, or a combination of both medications for 8 days, showed strong sterol disruption across all brain regions. We show ARI or TRZ alone elevated 7-DHC and decreased DES levels in all brain regions, but with regional differences. However, the combined utilization of these two medications for 8 days did not lead to additive changes in sterol disturbances. Based on the complex roles of 7-DHC derived oxysterols, we conclude that individual and potentially simultaneous use of medications with sterol biosynthesis-inhibiting properties might have undesired side effects on the adult brain, with as yet unknown long-term consequences on mental or physical health. American Society for Biochemistry and Molecular Biology 2022-07-14 /pmc/articles/PMC9386463/ /pubmed/35839864 http://dx.doi.org/10.1016/j.jlr.2022.100249 Text en © 2022 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Research Article
Balog, Marta
Anderson, Allison
Genaro-Mattos, Thiago C.
Korade, Zeljka
Mirnics, Karoly
Individual and simultaneous treatment with antipsychotic aripiprazole and antidepressant trazodone inhibit sterol biosynthesis in the adult brain
title Individual and simultaneous treatment with antipsychotic aripiprazole and antidepressant trazodone inhibit sterol biosynthesis in the adult brain
title_full Individual and simultaneous treatment with antipsychotic aripiprazole and antidepressant trazodone inhibit sterol biosynthesis in the adult brain
title_fullStr Individual and simultaneous treatment with antipsychotic aripiprazole and antidepressant trazodone inhibit sterol biosynthesis in the adult brain
title_full_unstemmed Individual and simultaneous treatment with antipsychotic aripiprazole and antidepressant trazodone inhibit sterol biosynthesis in the adult brain
title_short Individual and simultaneous treatment with antipsychotic aripiprazole and antidepressant trazodone inhibit sterol biosynthesis in the adult brain
title_sort individual and simultaneous treatment with antipsychotic aripiprazole and antidepressant trazodone inhibit sterol biosynthesis in the adult brain
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9386463/
https://www.ncbi.nlm.nih.gov/pubmed/35839864
http://dx.doi.org/10.1016/j.jlr.2022.100249
work_keys_str_mv AT balogmarta individualandsimultaneoustreatmentwithantipsychoticaripiprazoleandantidepressanttrazodoneinhibitsterolbiosynthesisintheadultbrain
AT andersonallison individualandsimultaneoustreatmentwithantipsychoticaripiprazoleandantidepressanttrazodoneinhibitsterolbiosynthesisintheadultbrain
AT genaromattosthiagoc individualandsimultaneoustreatmentwithantipsychoticaripiprazoleandantidepressanttrazodoneinhibitsterolbiosynthesisintheadultbrain
AT koradezeljka individualandsimultaneoustreatmentwithantipsychoticaripiprazoleandantidepressanttrazodoneinhibitsterolbiosynthesisintheadultbrain
AT mirnicskaroly individualandsimultaneoustreatmentwithantipsychoticaripiprazoleandantidepressanttrazodoneinhibitsterolbiosynthesisintheadultbrain