Studies have shown that people with dementia taking antipsychotics are at increased risk of serious health problems such as stroke and pneumonia, especially soon after starting treatment, highlighting the need to carefully evaluate and manage antipsychotic use in this vulnerable population.
Experts stress that extreme caution is needed in the early stages of treatment, as the risks are highest immediately after starting the medication.
Recently published studies BMJ The use of antipsychotics in people with dementia has been associated with a higher risk of many serious adverse events compared to not using them, including stroke, blood clots, heart attack, heart failure, fractures, pneumonia and acute kidney injury.
These findings indicate that harms associated with antipsychotic use in patients with dementia are considerably more widespread than previously recognized in regulatory warnings, and highlight the need for enhanced vigilance early in treatment, as risks are highest immediately after starting the medication.Despite safety concerns, antipsychotics continue to be widely prescribed to treat behavioral and psychological symptoms of dementia, including apathy, depression, aggression, anxiety, irritability, delirium, and psychosis.
Previous regulatory warnings on prescribing antipsychotics for these conditions are based on evidence of increased risk of stroke and death, but evidence of other adverse outcomes in dementia patients is inconclusive.
To address this uncertainty, the researchers decided to look at the risk of several adverse outcomes that may be associated with antipsychotic use in people with dementia: stroke, serious blood clots (venous thromboembolism), heart attack (myocardial infarction), heart failure, irregular heartbeat (ventricular arrhythmia), fractures, pneumonia, and acute kidney injury.
Study design and methodology
Using linked primary care, hospital and mortality data for England, the researchers identified 173,910 people (63% women) who were diagnosed with dementia between January 1998 and May 2018, were a mean age of 82 and had not been prescribed an antipsychotic in the year prior to diagnosis. Each of the 35,339 patients who had been prescribed an antipsychotic after their dementia diagnosis date was matched with up to 15 randomly selected patients who were not using antipsychotics.
Patients with a history of the specific outcome under investigation prior to diagnosis were excluded from the 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 influencing factors such as patients’ personal characteristics, lifestyle, medical conditions, and prescribed medications were also taken into account. Use of antipsychotics was associated with an increased risk of all outcomes, except ventricular arrhythmias, compared with non-users. For example, during the first 3 months of treatment, the incidence of pneumonia was 4.48% in antipsychotic users compared with 1.49% in non-users. After 1 year, this increased to 10.41% in antipsychotic users compared with 5.63% in non-users.
Antipsychotic users also had a higher risk of acute kidney injury (1.7-fold increased risk), stroke, and venous thromboembolism (1.6-fold increased risk) compared with non-users. For almost all outcomes, the highest risk occurred during the first week of antipsychotic treatment, especially for pneumonia.
The researchers estimated that during the first six months of treatment, antipsychotic use may increase one case of pneumonia for every nine treated patients and one heart attack for every 167 treated patients. After two years, it may increase one case of pneumonia for every 15 treated patients and one heart attack for every 254 treated patients.
Significance of the study
Because this is an observational study, no firm conclusions about causation can be drawn, and the researchers caution that misclassification of antipsychotic use may have occurred, and although they controlled for a range of factors, they cannot rule out the possibility that other unmeasured variables may have influenced the results.
However, this was a large analysis based on reliable health data, looked at a range of adverse events, and reported both relative and absolute risks across multiple time periods.
As such, the researchers say, antipsychotics are associated with a much wider range of serious adverse events than highlighted in previous regulatory warnings, with the highest risk occurring soon after treatment initiation, and are of direct relevance to guideline developers, regulators, clinicians, patients and their carers.
The potential benefits of antipsychotic treatment must be weighed against the risks of serious harm, and treatment plans should be regularly reviewed, the researchers add.
The findings will provide medical professionals with more detailed data to guide personalised treatment decisions, the US researchers said in an accompanying editorial.
International guidelines recommend restricting its use to adults with severe behavioural and psychological symptoms of dementia, but prescription rates have increased in recent years because there are relatively few effective non-drug alternative treatments and the significant resource costs required to implement them, the researchers explain.
“The time has come to prioritise more patient-centred care, tailored care plans, regular re-evaluation of management options and a move away from over-prescribing antipsychotics,” they conclude.
Reference: “Multiple Adverse Events Associated with Antipsychotic Use in Patients with Dementia: A Population-Based Matched Cohort Study”, 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, Darren M Ashcroft, April 17, 2024, BMJ.
Posted on: October 11, 2023
The research was funded by the National Institute for Health and Care Research (NIHR).
