Antipsychotics for dementia linked to ‘multiple adverse outcomes’
The use of antipsychotic drugs in patients with dementia is linked to more harms than currently acknowledged, which needs to be taken into account by prescribers, warn UK researchers.
They flagged that their findings showed a considerably wider range of harms associated with antipsychotic use in people with dementia than previously reflected in regulatory alerts.
“Absolute risk differences between antipsychotic users and their matched comparators were substantial for most adverse events”
Study authors
They found that antipsychotics were associated with elevated risks of serious adverse outcomes including stroke, blood clots, heart attack, heart failure, fracture, pneumonia and acute kidney injury.
According to the researchers, the risks were highest soon after starting the drugs, which they said “underscored” a need for increased caution in the early stages of treatment.
They noted that antipsychotics were widely prescribed for behavioural and psychological symptoms of dementia such as apathy, depression, aggression, anxiety, irritability, delirium and psychosis.
Previous regulatory warnings when prescribing antipsychotics for these symptoms were based on evidence of increased risks for stroke and death, said the study authors.
However, evidence of other adverse outcomes was previously less conclusive among people with dementia, highlighted the researchers in the British Medical Journal.
In order to address this apparent uncertainty, they set out to investigate the risks of several adverse outcomes potentially associated with antipsychotic use in people with dementia.
Using linked primary care, hospital and mortality data in England, they identified 173,910 patients with dementia, who had not been prescribed an antipsychotic in the year before their diagnosis.
Each of the 35,339 patients prescribed an antipsychotic on or after the date of their dementia diagnosis was then matched with up to 15 randomly selected patients who had not used the drugs.
The most commonly prescribed antipsychotics were risperidone, quetiapine, haloperidol, and olanzapine, which together accounted for almost 80% of all prescriptions.
The outcomes of interest to the researchers were stroke, venous thromboembolism, myocardial infarction, heart failure, ventricular arrhythmia, fractures, pneumonia and acute kidney injury.
Compared with non-use, antipsychotic use was associated with increased risks for all outcomes, except ventricular arrhythmia.
For example, in the first three months of treatment, rates of pneumonia among antipsychotic users were 4.48% versus 1.49% for non-users.
“Clinicians should actively consider the risks, considering patients’ pre-existing comorbidities and living support”
Study authors
At one year, this rose to 10.41% for antipsychotic users versus 5.63% for non-users, said the researchers.
Risks were also high among antipsychotic users for acute kidney injury, as well as stroke and venous thromboembolism compared with non-users.
For almost all outcomes, risks were highest during the first week of antipsychotic treatment, particularly for pneumonia, the researchers noted.
They estimated that, over the first six months of treatment, antipsychotic use might be associated with one additional case of pneumonia for every nine patients treated and one additional heart attack for every 167 patients treated.
At two years, there might be one additional case of pneumonia for every 15 patients treated and one additional heart attack for every 254 patients treated.
The researchers said: “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,” they said.
The authors stated: “Absolute risk differences between antipsychotic users and their matched comparators were substantial for most adverse events, and largest for pneumonia.”
As a result, they cautioned that any potential benefits of antipsychotic treatment needed “to be weighed against the risk of serious harm across multiple outcomes”.
“Although there may be times when an antipsychotic prescription is the least bad option, clinicians should actively consider the risks, considering patients’ pre-existing comorbidities and living support,” they added.
The research was a collaboration across the universities of Manchester, Nottingham, Edinburgh and Dundee
It was funded by the National Institute of Health and Care Research (NIHR) and the NIHR Greater Manchester Patient Safety Translational Research Centre, now the NIHR Greater Manchester Patient Safety Research Collaboration.
According to the National Institute for Health and Care Excellence, antipsychotics should only be prescribed for the treatment of behavioural and psychological symptoms of dementia if non-drug interventions have been ineffective, patients are at risk of harming themselves or others, or are experiencing agitation, hallucinations or delusions causing them severe distress.
