Cargando…

Seventy Years of Antipsychotic Development: A Critical Review

Since the mid-1950s discovery of the first effective antipsychotic medications (APM), we have only been able to improve the tolerability but not the overall efficacy of currently available APMs, as reflected by effectiveness trials in Europe and the United States. This inability to develop more effe...

Descripción completa

Detalles Bibliográficos
Autor principal: Shad, Mujeeb U.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9856208/
https://www.ncbi.nlm.nih.gov/pubmed/36672638
http://dx.doi.org/10.3390/biomedicines11010130
_version_ 1784873566828756992
author Shad, Mujeeb U.
author_facet Shad, Mujeeb U.
author_sort Shad, Mujeeb U.
collection PubMed
description Since the mid-1950s discovery of the first effective antipsychotic medications (APM), we have only been able to improve the tolerability but not the overall efficacy of currently available APMs, as reflected by effectiveness trials in Europe and the United States. This inability to develop more effective APMs is attributable to multiple factors, including failure to create and use assessment tools to assess core symptom domains in schizophrenia, move beyond the dopaminergic hypothesis and to develop “me too” drugs, imposing ill-defined research domain criteria, and lacking federal funding for clinical trials. The classification of APMs is also confusing, including second-generation, partial agonists, and multimodal APMs in the same class of APMs, despite significant differences in their mechanisms of action. Other factors stagnating drug development include inadequate sample sizes to address heterogeneity, lack of statistical measures correlating with clinical significance, using the atheoretical basis of psychiatric diagnoses, failure to control placebo response, and high cost of newer and perhaps more tolerable APMs. Furthermore, there has been a failure to develop early predictors of antipsychotic response and various tools to optimize an APM response. Finally, some mental health providers are also responsible for the suboptimal use of APMs, by using excessive maintenance doses, often with irrational polypharmacy, further compromising effectiveness and medication adherence. However, some bright spots in antipsychotic development include improved tolerability of APMs and long-acting injectables to address the high prevalence of medication nonadherence. This review critically reviews 70 years of antipsychotic development, the reasons behind the failure to develop more effective APMs, and suggestions for future direction.
format Online
Article
Text
id pubmed-9856208
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-98562082023-01-21 Seventy Years of Antipsychotic Development: A Critical Review Shad, Mujeeb U. Biomedicines Review Since the mid-1950s discovery of the first effective antipsychotic medications (APM), we have only been able to improve the tolerability but not the overall efficacy of currently available APMs, as reflected by effectiveness trials in Europe and the United States. This inability to develop more effective APMs is attributable to multiple factors, including failure to create and use assessment tools to assess core symptom domains in schizophrenia, move beyond the dopaminergic hypothesis and to develop “me too” drugs, imposing ill-defined research domain criteria, and lacking federal funding for clinical trials. The classification of APMs is also confusing, including second-generation, partial agonists, and multimodal APMs in the same class of APMs, despite significant differences in their mechanisms of action. Other factors stagnating drug development include inadequate sample sizes to address heterogeneity, lack of statistical measures correlating with clinical significance, using the atheoretical basis of psychiatric diagnoses, failure to control placebo response, and high cost of newer and perhaps more tolerable APMs. Furthermore, there has been a failure to develop early predictors of antipsychotic response and various tools to optimize an APM response. Finally, some mental health providers are also responsible for the suboptimal use of APMs, by using excessive maintenance doses, often with irrational polypharmacy, further compromising effectiveness and medication adherence. However, some bright spots in antipsychotic development include improved tolerability of APMs and long-acting injectables to address the high prevalence of medication nonadherence. This review critically reviews 70 years of antipsychotic development, the reasons behind the failure to develop more effective APMs, and suggestions for future direction. MDPI 2023-01-04 /pmc/articles/PMC9856208/ /pubmed/36672638 http://dx.doi.org/10.3390/biomedicines11010130 Text en © 2023 by the author. 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 Review
Shad, Mujeeb U.
Seventy Years of Antipsychotic Development: A Critical Review
title Seventy Years of Antipsychotic Development: A Critical Review
title_full Seventy Years of Antipsychotic Development: A Critical Review
title_fullStr Seventy Years of Antipsychotic Development: A Critical Review
title_full_unstemmed Seventy Years of Antipsychotic Development: A Critical Review
title_short Seventy Years of Antipsychotic Development: A Critical Review
title_sort seventy years of antipsychotic development: a critical review
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9856208/
https://www.ncbi.nlm.nih.gov/pubmed/36672638
http://dx.doi.org/10.3390/biomedicines11010130
work_keys_str_mv AT shadmujeebu seventyyearsofantipsychoticdevelopmentacriticalreview