Schizophrenia management: Systematic review of current medications and Phase-3 agents (2008–2024)

Salma Abdelmoteleb , Jayant Totlani , Salma Ramadan , Mohamed Salem , Ashley Meyer , Tiffany Chang , Madeline Ewing , Luiza Freire , Nathalie Murphy , Sabrina Renteria , Romana Dymkoski , Omer Liran , Rebecca Hedrick , Itai Danovitch , Robert N. Pechnick , Waguih William IsHak
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Abstract

This systematic review evaluates psychiatric medications for schizophrenia approved between 2008 and 2024, considering regulatory practices and approvals across multiple regions, including the United States, Europe, and Asian countries. It details the mechanism of action, indications, efficacy, dosing, and adverse effects of each medication. The methodology involved a literature search of the PubMed database for studies published from 2008 to December 31, 2024 on FDA-approved psychiatric medications and Phase 3 pipeline medications, along with additional medications approved in Europe using the keywords “schizophrenia” OR “psychosis” AND “psychopharm∗” OR “medic∗” OR “pharm∗.” An independent assessment was conducted, followed by a consensus on eligible studies for inclusion in the systematic review. From 2008 to December 31, 2024, the FDA approved 29 medications for schizophrenia including 13 long-acting injectables (LAI), in addition to that there are additional three other medications that are available in Europe but not in the United States. Additionally, 8 pipeline medications are currently in Phase-3 clinical trials including one LAI. Each medication is analyzed, and its mechanisms of action, indications, dosing, efficacy, and adverse effects are described. The 13 approved LAIs and the one LAI in the pipeline are detailed in a separate manuscript. This review highlights a significant increase in approved medications for the treatment of schizophrenia, including long-acting injectable formulations that enhance the range of existing oral therapies. Furthermore, new treatments for medication-related movement disorders have been introduced. Innovative developments in Phase-3 trials for schizophrenia medications, including new mechanisms of action and administration routes, promise to transform treatment strategies and enhance patient outcomes.
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