Antipsychotic usage in dementia linked to multiple adverse outcomes

Antipsychotics were found to be associated with an increased risk of stroke, heart failure, pneumonia and more.

Prescribing antipsychotics for people with dementia could cause more harm than previously thought, UK research suggests.

A population-based matched cohort study, published in The BMJ, shows the adverse effects of antipsychotics in dementia are not limited to cerebrovascular adverse events. Researchers found their usage was associated with a 22% increase in the risk of myocardial infarction, a 36% increase in the risk of fracture and a 103% increase in the risk of pneumonia.

“Risks of these wide-ranging adverse outcomes need to be considered before prescribing antipsychotic drugs to people with dementia,” the authors concluded.

The study, which combined primary care, hospital and deaths data from the Clinical Practice Research Datalink – identified 170,000 adults, aged over 50 years who were diagnosed with dementia.

After analysing up to 30 years of data and controlling for multiple confounders such as age, sex and comorbidities, researchers found antipsychotic use at any point after dementia diagnosis was associated with a 54% increase in the risk of stroke, a 52% increase in the risk of venous thromboembolism, a 22% increase in the risk of myocardial infarction, a 16% increase in the risk of heart failure, a 36% increase in the risk of facture, a 103% increase in the risk of pneumonia and a 57% increase in the risk of acute kidney injury. There was no association between antipsychotic use and the risk of ventricular arrhythmia.

The risk of an adverse event was greatest in the first 90 days after the antipsychotic was prescribed but declined with extended or ongoing antipsychotic usage.

One in five patients were prescribed an antipsychotic. The most prescribed antipsychotics were risperidone (30% of all prescriptions), quetiapine (29%) and haloperidol (11%).

The risk of stroke, heart failure, fracture, pneumonia and acute kidney injury were higher in patients taking typical (e.g., haloperidol) compared to atypical (e.g., risperidone, quetiapine) antipsychotics. Male antipsychotic users had an increased risk of pneumonia and kidney injury compared to female users but had a lower risk of stroke.

“By distinguishing between typical and atypical antipsychotic agents and detailing drug specific risks, the findings of this study will equip healthcare professionals with more nuanced data to help guide personalised treatment decisions,” wrote the authors of an accompanying editorial. 

The authors offered a potential explanation for the association between antipsychotic use and the increased risk of developing pneumonia.

“Antipsychotic induced extrapyramidal symptoms, sedation, xerostomia (dry mouth) and dyskinesia or impaired swallowing are commonly considered as potential risk factors [for pneumonia],” they wrote.

“It is [also] possible that reverse causality might have contributed to the high risks observed in the early days after drug initiation, as delirium from the onset of pneumonia might have been treated with antipsychotics before pneumonia was diagnosed.”

The BMJ 2024, online 18 April