A study has found that antipsychotic medications in dementia patients are associated with an increased risk of serious health problems, such as stroke and pneumonia, especially soon after starting treatment. This underscores the need for careful evaluation and management of antipsychotic use in this vulnerable population.
Experts stress the need for extra caution in the early stages of treatment, as the risks are greatest shortly after starting the medication.
A recently published study by The BMJ concludes that the use of antipsychotics in people with dementia is associated with an increased risk of several serious side effects, including stroke, blood clots, heart attack, heart failure, bone fractures, pneumonia and acute kidney injury, compared with not using them.
These findings demonstrate a significantly wider range of harms associated with antipsychotic use in people with dementia than previously recognised in regulatory warnings, with risks peaking soon after starting the drugs, highlighting the need for increased caution in the early stages of treatment. Despite safety concerns, antipsychotics continue to be widely prescribed for behavioural and psychological symptoms of dementia such as apathy, depression, aggression, anxiety, irritability, delirium and psychosis.
Previous regulatory warnings about prescribing antipsychotics for these symptoms are based on evidence of an increased risk of stroke and death. However, the evidence for other adverse effects is less clear in people with dementia.
To address this uncertainty, researchers set out to investigate the risks of several adverse outcomes that may be associated with antipsychotic use in people with dementia. The outcomes of interest were stroke, large blood clots (venous thromboembolism), heart attack (myocardial infarction), heart failure, irregular heartbeat (ventricular arrhythmia), fractures, pneumonia, and acute kidney injury.
Research design and methodology
Using linked primary care, hospital and mortality data in England, they identified 173,910 people (63% women) who were diagnosed with dementia between January 1998 and May 2018 at an average age of 82 and who had not been prescribed an antipsychotic in the year before their diagnosis. Each of the 35,339 patients who had been 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 taken an antipsychotic.
Patients with a history of the specific outcome being assessed before their diagnosis were excluded from analysis of that outcome. The most commonly prescribed antipsychotics were risperidone, quetiapine, haloperidol, and olanzapine, which together accounted for almost 80% of all prescriptions.
Potentially influential factors, including personal patient characteristics, lifestyle, pre-existing medical conditions, and prescribed medications, were also taken into account. 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. After one year, this increased to 10.41% for antipsychotic users versus 5.63% for non-users.
The risks were also high among antipsychotic users for acute kidney injury (1.7-fold increased risk), as well as stroke and venous thromboembolism (1.6-fold increased risk) compared with nonusers. For almost all outcomes, the risks were highest during the first week of antipsychotic treatment, particularly for pneumonia.
The researchers estimate that antipsychotic use in the first six months of treatment could be associated with one additional case of pneumonia for every nine patients treated and one additional heart attack for every 167 patients treated. After two years, there could be one additional case of pneumonia for every 15 patients treated and one additional heart attack for every 254 patients treated.
Implications of the study
This is an observational study, so no firm conclusions can be drawn about cause and effect, and the researchers cautioned that there may have been some misclassification of antipsychotic use. And while they adjusted for a range of factors, they can’t rule out the possibility that other unmeasured variables could have influenced their results.
However, this was a large-scale analysis based on reliable health data, examining a wide range of adverse events and reporting both relative and absolute risks over different time periods.
The researchers say antipsychotics are associated with a significantly wider range of serious adverse events than previously highlighted in regulatory warnings. The highest risks are seen shortly after starting treatment. They are therefore of immediate concern to guideline developers, regulators, clinicians, patients and their carers.
The potential benefits of antipsychotic treatment should be weighed against the risk of serious harm and treatment plans should be reviewed regularly, they add.
The findings of this study provide health care professionals with more nuanced data to help them make personalized treatment decisions, US researchers say in a linked editorial.
They explain that international guidelines recommend restricting use to adults with severe behavioural and psychological symptoms of dementia, but that the number of prescribers has increased in recent years. This is partly due to the relative shortage of effective, non-pharmacological alternatives and the significant resources required to implement them.
“There has long been a need for greater priority for more patient-centered care, tailored care plans, regular review of treatment options and a reduction in the overprescription of antipsychotics,” they conclude.
Reference: “Multiple adverse outcomes associated with antipsychotic use in people with dementia: population-based matched cohort study” by Pearl LH Mok, Matthew J Carr, Bruce Guthrie, Daniel R Morales, Aziz Sheikh, Rachel A Elliott, Elizabeth M Camacho, Tjeerd van Staa, Anthony J Avery and Darren M Ashcroft, April 17, 2024, BMJ.
DOI: 10.1136/bmj-2023-076268
The research was funded by the National Institute of Health and Care Research (NIHR).