“Association of metabolic syndrome in schizophrenia: a systematic comparison between atypical and typical antipsychotics”
DOI:
https://doi.org/10.69849/77y7az29Keywords:
Schizophrenia, Antipsychotic Agents, Metabolic Syndrome, Weight Gain, Systematic ReviewAbstract
Schizophrenia is a severe mental disorder characterized by symptoms such as hallucinations and blunted affect, requiring continuous pharmacological therapy with antipsychotics and lifelong psychological support. However, the adverse effects of these medications, both first- and second-generation, are closely associated with the development of Metabolic Syndrome (MetS), a complication that directly impacts patient survival. Therefore, this study aimed to evaluate the association between the use of atypical antipsychotics (second generation), compared to typical ones (first generation), and the incidence or prevalence of MetS in adults with schizophrenia. This is a systematic review guided by the PRISMA guidelines, with PICO-structured searches in PubMed, Embase, and LILACS databases. Clinical trials and observational studies (2021-2025) were included, with peer selection and data extraction using the Rayyan software. Seven studies comprised the final sample, encompassing over 20,000 patients. In the short to medium term, atypicals (especially olanzapine and clozapine) showed a substantially higher risk for MetS, inducing early insulin resistance via the elevation of macrophage migration inhibitory factor (MIF). However, strong intraclass heterogeneity was noted, with risperidone presenting a favorable metabolic profile. Long-term (5 years), the supposed safety superiority of typicals was not sustained: in individuals with baseline overweight, first-generation antipsychotics (such as haloperidol and thioridazine) induced obesity at rates (42% to 46%) equivalent to or higher than those of olanzapine. In conclusion, the classic dichotomy of metabolic safety between typical and atypical antipsychotics is inaccurate. Prescription requires strict individualization based on the patient's prior metabolic state (baseline BMI), making early and continuous cardiometabolic monitoring imperative, regardless of the adopted pharmacological class.
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Copyright (c) 2026 Pedro Leoncini Bussons, Lucas Antunes da Silva, Carolina Pontes Soares (Autor)
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