Adverse health events associated with antipsychotic use: an umbrella review

INTRODUCTION: Antipsychotic medications are prescribed in nearly 800,000 patients in England. Monitoring the adverse effects of antipsychotics is essential in the prevention of harm to patients. Numerous systematic reviews have found evidence for antipsychotics’ adverse effects, but few attempts have been made to assess the robustness of these evidence. This umbrella review aimed to grade and summarise the evidence for all adverse health events associated with antipsychotic use in the community settings, and assess the potential factors moderating the antipsychotic-adverse event associations, through the comparison across outcomes, quality assessments and identification of the current literature gaps.
METHODS: A systematic search was conducted on 6 databases (PubMed, Embase, PsycINFO, Scopus, CINAHL and Cochrane Library of Systematic Reviews). The risk of each adverse outcome was estimated with RRs or ORs. Subgroup analyses were conducted on the distinct classes and types of antipsychotics, age, diagnoses and study designs. The quality of the evidence of reported associations was examined via assessments on the extent of heterogeneity, 95% prediction intervals, small study effects and excess significance bias in the underlying review literature. The methodological quality of included meta-analyses was assessed with the AMSTAR 2 tool.
RESULTS: Twenty-seven meta-analyses of RCTs or observational studies were identified. The included meta-analyses of RCTs and observational studies reported statistically significant effect sizes for 26 adverse outcomes. Meta-analyses of RCTs found antipsychotics to increase the risk of endocrinological and metabolic, neuropsychiatric and movement-related outcomes. Meta-analyses on observational data found significant associations between antipsychotic use and injuries, circulatory system outcomes and mortality. Evidence was of variable quality, given the heterogenous findings, asymmetry in the funnel plots, and the diverse AMSTAR 2 ratings, prediction intervals and excess significance ratios. The most robust adverse outcomes were gait abnormality (RR 2.74, 95% CI 1.66 to 4.53) and hypertonia (RR 2.91, 95% CI 1.31 to 6.47). Other outcomes were supported by evidence of low-to-moderate quality. Subgroup analyses found atypical antipsychotics to be associated with the highest risk of adverse outcomes, compared to typical antipsychotics. Within SGAs, olanzapine was associated with a higher risk of adverse outcomes than quetiapine and risperidone. In terms of patient variables, older adults aged over 65 and patients with dementia were more likely to experience antipsychotic-associated adverse outcomes than adults and patients with schizophrenia.
CONCLUSIONS: Significant associations were found between antipsychotic use and a wide range of body functions. No conclusive evidence was found for how pharmacological and clinical factors impact on the occurrence of adverse outcomes due to the non-statistically significant difference between subgroups. The inconsistent quality of current evidence demonstrated the need for better conducted studies following reporting guidelines in evaluating the harm profiles of antipsychotics.

Keywords: side effect
antipsychotic
adverse event
umbrella review
psychiatric medication
psychopharmacology
meta review
psychiatry
Advisor: Fazel, S
Paljärvi, T