DEPRESSÃO, ANSIEDADE E IDEAÇÃO SUICIDA EM PACIENTES EM USO DE AGONISTAS DO RECEPTOR GLP-1: UMA REVISÃO SISTEMÁTICA DAS EVIDÊNCIAS CLÍNICAS E DOS MECANISMOS NEUROBIOLÓGICOS ENVOLVIDOS

ABSTRACT Glucagon-like peptide-1 (GLP-1) receptor agonists are widely used for the treatment of type 2 diabetes mellitus and, more recently, obesity, owing to their well-established metabolic, cardiovascular, and weight-loss benefits. However, the rapid expansion of their clinical use has raised growing concerns regarding potential psychiatric effects, including depression, anxiety, and suicidal ideation, particularly among psychosocially vulnerable populations. This systematic review aimed to synthesize the available clinical evidence on the association between GLP-1 receptor agonist use and psychiatric outcomes, as well as to discuss the underlying neurobiological mechanisms. A comprehensive literature search was conducted in PubMed/MEDLINE, Scopus, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov, including studies published between 2015 and 2025, in accordance with PRISMA 2020 guidelines. Twenty-eight studies were included, comprising randomized controlled trials, observational studies, and pharmacovigilance analyses, encompassing more than 42,000 individuals. Randomized controlled trials did not demonstrate a consistent increase in the risk of depression, anxiety, or suicidal ideation compared with control groups. Observational studies reported stability or improvement in depressive symptoms, particularly among individuals achieving significant weight loss. Conversely, pharmacovigilance analyses identified safety signals related to suicidal ideation, especially in obesity treatment settings, although without conclusive evidence of causality. In conclusion, while current evidence does not support a consistent association between GLP-1 receptor agonists and adverse psychiatric outcomes, heterogeneity across studies and methodological limitations highlight the need for individualized clinical monitoring and dedicated prospective studies focusing on neuropsychiatric safety.