Obstructive sleep apnea as a potential mechanistic link between second-generation antipsychotics and metabolic syndrome: a narrative review

Abstract

This narrative review examines why metabolic syndrome is highly prevalent among individuals treated with second-generation antipsychotics (SGAs), yet weight gain alone does not fully explain this elevated risk. Metabolic disturbances frequently emerge soon after antipsychotic initiation, even without clinically significant changes in body mass, suggesting weight-independent mechanisms. Emerging evidence indicates that SGAs may influence respiratory regulation and increase vulnerability to obstructive sleep apnea (OSA), a common but underrecognized comorbidity in psychiatric populations. OSA contributes to metabolic dysfunction through recurrent nocturnal hypoxia, inflammation, sympathetic activation, and impaired glucose regulation, raising the possibility that SGA-related alterations in breathing could precipitate or exacerbate OSA thereby accelerating metabolic deterioration. Observational studies report higher OSA prevalence among individuals with psychiatric disorders and suggest that SGA use may increase OSA risk independently of adiposity. Proposed mechanisms include SGA-induced reductions in upper-airway muscle tone, alterations in ventilatory control, and metabolic disturbances such as insulin resistance, each of which may heighten airway collapsibility or breathing instability. Collectively, these findings support the hypothesis that OSA may represent a mechanistic link between SGA exposure and metabolic syndrome. Clarifying this relationship could identify a modifiable pathway and inform screening and treatment strategies aimed at reducing cardiometabolic and psychiatric burden in SGA-treated populations.