Use of antipsychotic medications in patients with dementia is linked with a much wider range of serious harms than previously thought, say UK researchers.
Although there have been safety warnings on use of the antipsychotics from regulators about increased risk of stroke and death, a large study has now found increased risks for pneumonia, venous thromboembolism, heart attack, heart failure, fracture, and acute kidney injury.
Reporting the findings in the BMJ, researchers from the University of Manchester said it underscores the need for increased caution when prescribing.
The study compared linked primary care, hospital, and mortality data for 173,901 patients with dementia of whom 35,339 had been prescribed an antipsychotic on or after the date of their dementia diagnosis.
Risperidone, quetiapine, haloperidol, and olanzapine accounted for almost 80% of all prescriptions.
The analysis showed that antipsychotic use was associated with increased risks for all outcomes looked at with the exception of ventricular arrhythmia.
Over the first six months of treatment, it was estimated that antipsychotic use was linked with one additional case of pneumonia for every nine patients treated, and one additional heart attack for every 167 patients treated.
After two years, the figures were one additional case of pneumonia for every 15 patients treated, and one extra heart attack for every 254 patients treated.
For almost all outcomes, risks were highest during the first week of antipsychotic treatment, and this was particularly true for pneumonia, they reported.
Study author Professor Darren Ashcroft, director of the National Institute for Health Research (NIHR) Greater Manchester Patient Safety Translational Research Centre, said in recent years, it had become clear that more people with dementia were 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.’
Co-investigator Professor Tony Avery, professor of primary health care at the University of Nottingham and also the national clinical director for prescribing said for many years there had been safety concerns about the use of antipsychotics for dementia with increased risk of stroke and death being reported.
‘Our study shows that the use of antipsychotics in this group of patients is also associated with other harms including pneumonia, venous thromboembolism, myocardial infarction, heart failure, fracture, and acute kidney injury.
‘This means that it is even more important to take account of risk of harm when considering prescribing these medicines, and to use alternative approaches wherever possible.’
Professor Charles Marshall, professor of clinical neurology at Queen Mary University of London, said the study findings should prompt renewed efforts to reduce the prescribing of antipsychotics to people living with dementia.
‘There are rare circumstances where antipsychotics are genuinely required, and the benefits outweigh these risks, but for the majority of patients with behavioural symptoms that might lead to them being prescribed anti-psychotics, we should be focussing on much safer behavioural management approaches.
‘The problem is that this type of intervention is quite expensive and resource-intensive. There is a risk therefore that patients might be prescribed harmful antipsychotics simply because trained staff who can safely manage their behaviour are not sufficiently available.’
Dr Sheona Scales, director of research at Alzheimer’s Research UK, said concerns about anti-psychotics had been known for some time and the latest findings were particularly concerning given the increase in prescribing seen in the pandemic.
‘The distressing symptoms of dementia, such as confusion and agitation, pose significant challenges for people living with dementia, their families, and caregivers.
‘Treatments that can help manage these symptoms are essential for a better quality of life, but options are currently limited, and in certain circumstances antipsychotics can be used to treat severe symptoms.
‘With nearly one million people affected by dementia in the UK, there is an urgent need for research to develop safer and more effective treatments.’
It must always be remembered that people with dementia (and those without) are liable to an increase in agitation, confusion, wandering, and hallucinations in certain medical situations, notably infections such as UTI and URTI. The latter is often a prodrome to a pneumonia, which is a well-known cause of delirium.
It therefore begs the question whether those who developed pneumonia within a week of starting a new antipsychotic medication did not really do so as a result of their medication, but developed symptoms requiring antipsychotic as a result of their infective medical condition.
This seems to be particularly the case with Covid, where acute covid infection can cause strange mental effects (please do NOT drive to Castle Barnard just to check if you are fit to drive or not), and also unpredictably can cause pneumonias.
At the same time, some of those noted side effects can be a result of sedation and reduced mobility, so one wonders if they are side effets truly of the drug, or side effects of too high a dose?
Ideally, one would wish to see further research detailing the variation in rates of these serious side effects with different antipsychotics, and excluding potential infective causes of behavioural need for them, before we can be sure how we should change prescribing behaviour, in situations where, as noted in the article, there may be a balance of risk in favour of prescribing them.