Third-Generation Antipsychotics: The Quest for the Key to Neurotrophism

Antipsychotic drugs (APs) have profoundly changed the treatment landscape for psychiatric disorders, yet their impact on neuroplasticity and neurotrophism remains only partially understood. While second-generation antipsychotics (SGAs) are associated with a better side effect profile than their pred...

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Main Authors: Federico Mucci, Alessandro Arone, Riccardo Gurrieri, Francesco Weiss, Gerardo Russomanno, Donatella Marazziti
Format: Article
Language:English
Published: MDPI AG 2025-03-01
Series:Life
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Online Access:https://www.mdpi.com/2075-1729/15/3/391
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author Federico Mucci
Alessandro Arone
Riccardo Gurrieri
Francesco Weiss
Gerardo Russomanno
Donatella Marazziti
author_facet Federico Mucci
Alessandro Arone
Riccardo Gurrieri
Francesco Weiss
Gerardo Russomanno
Donatella Marazziti
author_sort Federico Mucci
collection DOAJ
description Antipsychotic drugs (APs) have profoundly changed the treatment landscape for psychiatric disorders, yet their impact on neuroplasticity and neurotrophism remains only partially understood. While second-generation antipsychotics (SGAs) are associated with a better side effect profile than their predecessors, the emergence of third-generation antipsychotics (TGAs)—such as brexpiprazole, cariprazine, lurasidone, iloperidone, lumateperone, pimavanserin, and roluperidone—has prompted renewed interest in their potential neuroprotective and pro-cognitive effects. This review attempts to carefully examine the evidence on the neurotrophic properties of TGAs and their role in modulating brain plasticity by analyzing studies published between 2010 and 2024. Although data remain limited and focused primarily on earlier SGAs, emerging findings suggest that some TGAs may exert positive effects on neuroplastic processes, including the modulation of brain-derived neurotrophic factors (BDNFs) and synaptic architecture. However, robust clinical data on their long-term effects and comparative efficacy are lacking; therefore, further research is necessary to validate their role in preventing neurodegenerative changes and improving cognitive outcomes in patients with psychiatric conditions.
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spelling doaj-art-0831e0984b78445da8f36f25eba2e6f82025-08-20T01:48:52ZengMDPI AGLife2075-17292025-03-0115339110.3390/life15030391Third-Generation Antipsychotics: The Quest for the Key to NeurotrophismFederico Mucci0Alessandro Arone1Riccardo Gurrieri2Francesco Weiss3Gerardo Russomanno4Donatella Marazziti5Department of Psychiatry, Lucca Zone, Azienda USL Toscana Nord Ovest, 55100 Lucca, ItalyDepartment of Clinical and Experimental Medicine, Section of Psychiatry, University of Pisa, 56100 Pisa, ItalyDepartment of Clinical and Experimental Medicine, Section of Psychiatry, University of Pisa, 56100 Pisa, ItalyDepartment of Clinical and Experimental Medicine, Section of Psychiatry, University of Pisa, 56100 Pisa, ItalyDepartment of Clinical and Experimental Medicine, Section of Psychiatry, University of Pisa, 56100 Pisa, ItalyDepartment of Clinical and Experimental Medicine, Section of Psychiatry, University of Pisa, 56100 Pisa, ItalyAntipsychotic drugs (APs) have profoundly changed the treatment landscape for psychiatric disorders, yet their impact on neuroplasticity and neurotrophism remains only partially understood. While second-generation antipsychotics (SGAs) are associated with a better side effect profile than their predecessors, the emergence of third-generation antipsychotics (TGAs)—such as brexpiprazole, cariprazine, lurasidone, iloperidone, lumateperone, pimavanserin, and roluperidone—has prompted renewed interest in their potential neuroprotective and pro-cognitive effects. This review attempts to carefully examine the evidence on the neurotrophic properties of TGAs and their role in modulating brain plasticity by analyzing studies published between 2010 and 2024. Although data remain limited and focused primarily on earlier SGAs, emerging findings suggest that some TGAs may exert positive effects on neuroplastic processes, including the modulation of brain-derived neurotrophic factors (BDNFs) and synaptic architecture. However, robust clinical data on their long-term effects and comparative efficacy are lacking; therefore, further research is necessary to validate their role in preventing neurodegenerative changes and improving cognitive outcomes in patients with psychiatric conditions.https://www.mdpi.com/2075-1729/15/3/391neuroplasticityneurotrophismthird-generation antipsychoticsbrexpiprazolecariprazinelurasidone
spellingShingle Federico Mucci
Alessandro Arone
Riccardo Gurrieri
Francesco Weiss
Gerardo Russomanno
Donatella Marazziti
Third-Generation Antipsychotics: The Quest for the Key to Neurotrophism
Life
neuroplasticity
neurotrophism
third-generation antipsychotics
brexpiprazole
cariprazine
lurasidone
title Third-Generation Antipsychotics: The Quest for the Key to Neurotrophism
title_full Third-Generation Antipsychotics: The Quest for the Key to Neurotrophism
title_fullStr Third-Generation Antipsychotics: The Quest for the Key to Neurotrophism
title_full_unstemmed Third-Generation Antipsychotics: The Quest for the Key to Neurotrophism
title_short Third-Generation Antipsychotics: The Quest for the Key to Neurotrophism
title_sort third generation antipsychotics the quest for the key to neurotrophism
topic neuroplasticity
neurotrophism
third-generation antipsychotics
brexpiprazole
cariprazine
lurasidone
url https://www.mdpi.com/2075-1729/15/3/391
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