In a recent British Medical Journal study, researchers are evaluating side effects associated with the use of antipsychotic drugs in people with dementia.
Study: Multiple adverse events associated with antipsychotic use in people with dementia: a population-based matched cohort study. Image credit: Fahroni / Shutterstock.com
The role of antipsychotics in the management of dementia
People diagnosed with dementia experience functional disability and progressive cognitive decline. Some common psychological and behavioral symptoms of dementia include anxiety, depression, apathy, aggression, delirium, irritability, and psychosis.
To manage the psychological and behavioral symptoms of dementia, patients are usually treated with antipsychotics. The UK National Institute for Health and Care Excellence currently recommends the use of antipsychotics only when non-pharmacological interventions are ineffective in alleviating the behavioral and psychological symptoms of dementia. However, there has been an increase in the use of antipsychotics during the recent coronavirus disease 2019 (COVID-19) pandemic, which has been attributed to containment measures and the unavailability of non-pharmacological treatments.
In the UK, risperidone and haloperidol are the only antipsychotics approved for the treatment of behavioral or psychological symptoms of dementia. In 2003, the United States Food and Drug Administration (FDA) highlighted the risks, including stroke, transient ischemic attack, and mortality, associated with the use of risperidone in older adults with dementia.
Based on many study reports, regulatory guidelines have been formulated in the UK, USA and Europe to reduce the inappropriate prescribing of antipsychotics for the treatment of behavioral and psychological symptoms of dementia. To date, few studies have provided evidence of the association between antipsychotic drug prescription in older adults with dementia and risks of multiple diseases, including myocardial infarction, venous thromboembolism, ventricular arrhythmia, and acute kidney injury.
About the study
The current study investigated the risk of adverse outcomes associated with antipsychotics in a large cohort of adults with dementia. Some adverse outcomes examined in this study were venous thromboembolism, stroke, heart failure, ventricular arrhythmia, fracture, myocardial infarction, pneumonia, and acute kidney injury.
Over 98% of the UK population is registered with a National Health Service (NHS) Primary Care General Practice. All relevant data were collected from electronic health records held in the Clinical Practice Research Datalink (CPRD), which is associated with more than 2,000 general practices. The CPRD includes the Aurum and GOLD databases, which can be considered to be broadly representative of the UK population.
People over the age of 50 and diagnosed with dementia were selected. Importantly, none of the study participants were under antipsychotic intervention in the year prior to their diagnosis.
The researchers used a cohort-matching design, in which every patient who used antipsychotics after their initial diagnosis of dementia was matched using the incidence density sampling method. This method looked at up to 15 randomly selected patients who were diagnosed with dementia on the same date but were not prescribed antipsychotic medication.
Antipsychotics increase the risk of adverse effects in patients with dementia
Across both groups, the mean age of participants was 82.1 years. A total of 35,339 participants were prescribed an antipsychotic during the study period.
The mean number of days between the first diagnosis of dementia and the date of the first antipsychotic prescription was 693.8 and 576.6 days for Aurum and GOLD, respectively. The most commonly prescribed antipsychotics were risperidone, haloperidol, olanzapine and quetiapine.
The current population-based study revealed that adults with dementia who were prescribed antipsychotics were at greater risk of venous thromboembolism, myocardial infarction, stroke, heart failure, pneumonia, fracture, and acute kidney injury than nonusers. This observation was based on the analysis of 173,910 adults with dementia selected from both databases.
The increased risk of adverse outcomes was more prevalent among current and recent users of antipsychotic medications. After 90 days of antipsychotic use, the risk of venous thromboembolism, pneumonia, acute kidney injury and stroke was higher than non-users. However, antipsychotic drugs did not affect the risk of ventricular arrhythmia, appendicitis, and cholecystitis.
Compared with the use of risperidone, haloperidol was significantly associated with an increased risk of pneumonia, fracture, and acute kidney injury. Although the adverse effects of haloperidol were higher than quetiapine, no significant differences were observed between risperidone and quetiapine for the risk of fracture, heart failure, and myocardial infarction. The risk of pneumonia, stroke, acute kidney injury and venous thromboembolism was lower for quetiapine compared to risperidone.
conclusions
The current study highlights how antipsychotic drugs affect older people with dementia. The use of these drugs was associated with many serious adverse outcomes, including stroke, acute kidney injury, pneumonia, venous thromboembolism, heart failure, and myocardial infarction.
In the future, these risks should be considered, along with stroke and mortality, when making regulatory decisions about the use of antipsychotic drugs to treat dementia in older adults.
Journal Reference:
- Mok, LHP, Carr, MJ, Guthrie, B., et al. (2024) Multiple adverse outcomes associated with antipsychotic use in people with dementia: a population-based matched cohort study. BMJ. doi:10.1136/bmj.2023.076268
