Comparative analysis of third-generation antipsychotics in first-episode schizophrenia: efficacy, safety, and cognitive impacts. A narrative review

Background and objectives Schizophrenia is a chronic, complex mental health disorder requiring effective management to mitigate its broad personal and societal impacts. This narrative review assesses the efficacy, effectiveness, and side effects of third-generation antipsychotics (TGAs) like aripiprazole, brexpiprazole, and cariprazine, focusing on their use in first-episode schizophrenia. These drugs aim to reduce side effects typical of earlier antipsychotics while more effectively addressing positive and cognitive symptoms. Methods Our extensive literature review, using PubMed and Scopus , includes randomized controlled trials and observational studies, showing TGAs may match older antipsychotics in efficacy with fewer side effects, notably in reducing extrapyramidal symptoms and enhancing cognitive outcomes. Results Aripiprazole appears effective in both acute and maintenance phases of schizophrenia, while brexpiprazole and cariprazine show potential in managing negative symptoms and improving social functioning, essential for patient recovery. Conclusions This review emphasizes the need for personalized treatment and further research to fully determine the long-term benefits and safety of TGAs. These findings can inform clinical decisions and underline the ongoing need for innovation in schizophrenia pharmacotherapy.