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Combination of antidepressants and antipsychotics as a novel treatment option for psychosis in Alzheimer's disease

Psychotic symptoms are reported as one of the most common complications of Alzheimer's disease (AD), in whom they are associated with more rapid deterioration and increased mortality. Empiric treatments, namely first and second‐generation antipsychotics, confer modest efficacy in patients with...

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Autores principales: Fan, Peihao, Zeng, Lang, Ding, Ying, Kofler, Julia, Silverstein, Jonathan, Krivinko, Joshua, Sweet, Robert A., Wang, Lirong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10431054/
https://www.ncbi.nlm.nih.gov/pubmed/37128639
http://dx.doi.org/10.1002/psp4.12979
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author Fan, Peihao
Zeng, Lang
Ding, Ying
Kofler, Julia
Silverstein, Jonathan
Krivinko, Joshua
Sweet, Robert A.
Wang, Lirong
author_facet Fan, Peihao
Zeng, Lang
Ding, Ying
Kofler, Julia
Silverstein, Jonathan
Krivinko, Joshua
Sweet, Robert A.
Wang, Lirong
author_sort Fan, Peihao
collection PubMed
description Psychotic symptoms are reported as one of the most common complications of Alzheimer's disease (AD), in whom they are associated with more rapid deterioration and increased mortality. Empiric treatments, namely first and second‐generation antipsychotics, confer modest efficacy in patients with AD and with psychosis (AD+P) and themselves increase mortality. Recent studies suggested the use and beneficial effects of antidepressants among patients with AD+P. This motivates our rationale for exploring their potential as a novel combination therapy option among these patients. We included electronic medical records of 10,260 patients with AD in our study. Survival analysis was performed to assess the effects of the combination of antipsychotics and antidepressants on the mortality of these patients. A protein–protein interaction network representing AD+P was built, and network analysis methods were used to quantify the efficacy of these drugs on AD+P. A combined score was developed to measure the potential synergetic effect against AD+P. Our survival analyses showed that the co‐administration of antidepressants with antipsychotics have a significant beneficial effect in reducing mortality. Our network analysis showed that the targets of antipsychotics and antidepressants are well‐separated, and antipsychotics and antidepressants have similar Signed Jaccard Index (SJI) scores to AD+P. Eight drug pairs, including some popular recommendations like aripiprazole/sertraline, showed higher than average scores which suggest their potential in treating AD+P via strong synergetic effects. Our proposed combinations of antipsychotic and antidepressant therapy showed a strong superiority over current antipsychotics treatment for AD+P. The observed beneficial effects can be further strengthened by optimizing drug‐pair selection based on our systems pharmacology analysis.
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spelling pubmed-104310542023-08-17 Combination of antidepressants and antipsychotics as a novel treatment option for psychosis in Alzheimer's disease Fan, Peihao Zeng, Lang Ding, Ying Kofler, Julia Silverstein, Jonathan Krivinko, Joshua Sweet, Robert A. Wang, Lirong CPT Pharmacometrics Syst Pharmacol Research Psychotic symptoms are reported as one of the most common complications of Alzheimer's disease (AD), in whom they are associated with more rapid deterioration and increased mortality. Empiric treatments, namely first and second‐generation antipsychotics, confer modest efficacy in patients with AD and with psychosis (AD+P) and themselves increase mortality. Recent studies suggested the use and beneficial effects of antidepressants among patients with AD+P. This motivates our rationale for exploring their potential as a novel combination therapy option among these patients. We included electronic medical records of 10,260 patients with AD in our study. Survival analysis was performed to assess the effects of the combination of antipsychotics and antidepressants on the mortality of these patients. A protein–protein interaction network representing AD+P was built, and network analysis methods were used to quantify the efficacy of these drugs on AD+P. A combined score was developed to measure the potential synergetic effect against AD+P. Our survival analyses showed that the co‐administration of antidepressants with antipsychotics have a significant beneficial effect in reducing mortality. Our network analysis showed that the targets of antipsychotics and antidepressants are well‐separated, and antipsychotics and antidepressants have similar Signed Jaccard Index (SJI) scores to AD+P. Eight drug pairs, including some popular recommendations like aripiprazole/sertraline, showed higher than average scores which suggest their potential in treating AD+P via strong synergetic effects. Our proposed combinations of antipsychotic and antidepressant therapy showed a strong superiority over current antipsychotics treatment for AD+P. The observed beneficial effects can be further strengthened by optimizing drug‐pair selection based on our systems pharmacology analysis. John Wiley and Sons Inc. 2023-05-11 /pmc/articles/PMC10431054/ /pubmed/37128639 http://dx.doi.org/10.1002/psp4.12979 Text en © 2023 The Authors. CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Research
Fan, Peihao
Zeng, Lang
Ding, Ying
Kofler, Julia
Silverstein, Jonathan
Krivinko, Joshua
Sweet, Robert A.
Wang, Lirong
Combination of antidepressants and antipsychotics as a novel treatment option for psychosis in Alzheimer's disease
title Combination of antidepressants and antipsychotics as a novel treatment option for psychosis in Alzheimer's disease
title_full Combination of antidepressants and antipsychotics as a novel treatment option for psychosis in Alzheimer's disease
title_fullStr Combination of antidepressants and antipsychotics as a novel treatment option for psychosis in Alzheimer's disease
title_full_unstemmed Combination of antidepressants and antipsychotics as a novel treatment option for psychosis in Alzheimer's disease
title_short Combination of antidepressants and antipsychotics as a novel treatment option for psychosis in Alzheimer's disease
title_sort combination of antidepressants and antipsychotics as a novel treatment option for psychosis in alzheimer's disease
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10431054/
https://www.ncbi.nlm.nih.gov/pubmed/37128639
http://dx.doi.org/10.1002/psp4.12979
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