An umbrella review of adverse effects associated with antipsychotic medications: the need for complementary study designs

Antipsychotic medications are widely prescribed in psychotic illnesses and other mental disorders. Effectiveness is well-established, particularly for reducing symptoms such as delusions and hallucinations, but can be impacted by tolerability. Adverse effects are wide-ranging, and vary between antipsychotics, which is clinically important. This umbrella review aimed to comprehensively summarise the extent and quality of evidence for adverse effects associated with antipsychotic use in people with mental disorders. We included 32 meta-analyses of randomised trials and observational studies. The overall robustness of reported associations was considered in terms of review quality, heterogeneity, excess significance bias, and prediction intervals. Using this approach, endocrine and metabolic, movement-related, and sedation and sleep problems were the clinical domains with strongest evidence. The overall quality of included meta-analyses was low, and individual adverse effects were not typically examined in meta-analyses of both randomised trials and observational study designs. Future reviews should focus on adhering to methodological guidelines, consider the complementary strengths of different study designs, and integrate clinically relevant information on absolute rates and severity of adverse effects.