Doctors are being urged to reduce prescribing of antipsychotic drugs to dementia patients after the largest study of its kind found they were linked to more harmful side effects than previously thought.
The powerful medications are widely prescribed for behavioural and psychological symptoms of dementia like apathy, depression, aggression, anxiety, irritability, delirium and psychosis. Tens of thousands of dementia patients in England are prescribed them every year.
Although safety concerns have previously been raised about the drugs, with warnings to medics based on increased risks for stroke and death, evidence of other dangers was less conclusive, reports The Guardian.
Now, the recent research from British scientists suggests a considerably wider range of harms linked to their use than previously acknowledged in regulatory alerts, underscoring the need for increased caution in the early stages of treatment.
The study showed elevated risks of a wide range of serious adverse outcomes, including stroke, blood clots, heart attack, heart failure, fracture, pneumonia and acute kidney injury, the authors reported in their findings, published in The BMJ.
The team examined data from 174 000 adults registered at GP surgeries in England who were diagnosed with dementia between 1998 and 2018.
During the study, 35 339 were prescribed antipsychotics – 63% of whom were women – and their medical records were compared with those of dementia patients who were not prescribed these drugs.
Academics from Manchester, Nottingham, Edinburgh and Dundee universities found that patients using antipsychotic drugs had a twofold increased risk of developing pneumonia compared with those who were not.
They also found that dementia patients on antipsychotics had a 61% increased risk of stroke and a 43% elevated risk of breaking a bone, while there was a 28% increased risk of heart attack and 27% increased risk of heart failure.
The patients also appeared to have a 72% increased risk of kidney injury and 62% increased risk of developing a type of blood clot called a venous thromboembolism. The elevated risks appeared to be highest in the first week after treatment.
The study was observational so no firm conclusions could be made about cause and effect. But the authors wrote: “The range of adverse outcomes was wider than previously highlighted in regulatory alerts, with the highest risks soon after initiation of treatment.”
Professor Darren Ashcroft, the study’s senior author, from the University of Manchester, said: “In recent years, it has become clear that more people with dementia are being prescribed antipsychotic drugs, despite existing regulatory safety warnings.
“It is important that any potential benefits of antipsychotic treatment are weighed carefully against the risk of serious harm, and treatment plans need to be regularly reviewed in all health and care settings.”
Study details
Multiple adverse outcomes associated with antipsychotic use in people with dementia: population based matched cohort study
Pearl Mok, Matthew Carr, Darren Ashcroft et al.
Published in The BMJ on 17 April 2024
Abstract
Objective
To investigate risks of multiple adverse outcomes associated with use of antipsychotics in people with dementia.
Design
Population based matched cohort study.
Setting
Linked primary care, hospital and mortality data from Clinical Practice Research Datalink (CPRD), England.
Population
Adults (≥50 years) with a diagnosis of dementia between 1 January 1998 and 31 May 2018 (n=173 910, 63.0% women). Each new antipsychotic user (n=35 339, 62.5% women) was matched with up to 15 non-users using incidence density sampling.
Main outcome measures
The main outcomes were stroke, venous thromboembolism, myocardial infarction, heart failure, ventricular arrhythmia, fracture, pneumonia, and acute kidney injury, stratified by periods of antipsychotic use, with absolute risks calculated using cumulative incidence in antipsychotic users versus matched comparators. An unrelated (negative control) outcome of appendicitis and cholecystitis combined was also investigated to detect potential unmeasured confounding.
Results
Compared with non-use, any antipsychotic use was associated with increased risks of all outcomes, except ventricular arrhythmia. Current use (90 days after a prescription) was associated with elevated risks of pneumonia (hazard ratio 2.19, 95% confidence interval (CI) 2.10 to 2.28), acute kidney injury (1.72, 1.61 to 1.84), venous thromboembolism (1.62, 1.46 to 1.80), stroke (1.61, 1.52 to 1.71), fracture (1.43, 1.35 to 1.52), myocardial infarction (1.28, 1.15 to 1.42), and heart failure (1.27, 1.18 to 1.37). No increased risks were observed for the negative control outcome (appendicitis and cholecystitis). In the 90 days after drug initiation, the cumulative incidence of pneumonia among antipsychotic users was 4.48% (4.26% to 4.71%) versus 1.49% (1.45% to 1.53%) in the matched cohort of non-users (difference 2.99%, 95% CI 2.77% to 3.22%).
Conclusions
Antipsychotic use compared with non-use in adults with dementia was associated with increased risks of stroke, venous thromboembolism, myocardial infarction, heart failure, fracture, pneumonia, and acute kidney injury, but not ventricular arrhythmia. The range of adverse outcomes was wider than previously highlighted in regulatory alerts, with the highest risks soon after initiation of treatment.
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