Long-Term Antipsychotic Use and Cardiometabolic Adverse Effects in Adults with Non-Psychotic Disorders: A Systematic Review

Background Off-label antipsychotic prescribing for non-psychotic disorders is increasing, often at low doses and over extended periods. While cardiometabolic adverse effects are documented among individuals treated with antipsychotics for psychotic disorders, the consequences of long-term off-label antipsychotic use are not well-known. This systematic review synthesises evidence for cardiometabolic adverse effects of long-term antipsychotic therapy in adults and the elderly with non-psychotic disorders. Methods We searched electronic databases for randomised controlled trials or observational studies of ≥1 year duration. Adverse events included weight gain, hyperglycaemia, dyslipidaemia, hypertension, metabolic syndrome, ischaemic heart disease, thrombosis and cardiometabolic mortality. Results : We found 13 observational studies with high heterogeneity. Among adults, antipsychotic-treated individuals displayed increased prevalence of weight gain (28.8–77.9%), hyperglycaemia (4.8–23.2%) and dyslipidaemia (15.8–47.5%) compared with untreated patients. Second-generation antipsychotics had a larger effect than first-generation agents. A weak association was observed for cardiometabolic mortality. Results were sparse for the elderly, with one study indicating increased prevalence of metabolic syndrome and its components, and an inverse correlation of treatment duration with the risk for myocardial infarction. Studies were judged to have moderate-high methodological quality using suitable standardised risk of bias assessment tools. Conclusions : Despite heterogeneity in included studies, this review highlights adverse cardiometabolic outcomes associated with long-term antipsychotic use in adults with non-psychotic disorders, which is concerning given the high proportion of off-label use. Clinicians should exercise caution when prescribing antipsychotics off-label, especially where alternative options are available, and support even low-dose use with regular metabolic monitoring.