medwireNews: The use of antipsychotic medications for the treatment of behavioral and psychological symptoms in patients with dementia is associated with a broader range of adverse outcomes than are currently listed in regulatory warnings, suggests a recent study.
“[A]ntipsychotics continue to be frequently prescribed for the management of behavioral and psychological symptoms of dementia,” despite safety concerns, which are currently “based on evidence of increased risk of stroke and death,” explain Pearl Mok (University of Manchester and Manchester Academic Health Science Center, UK) and colleagues in The BMJ.
However, they found that antipsychotic use in people with dementia is also associated with an increased risk for pneumonia, acute kidney injury, venous thromboembolism, fracture, myocardial infarction, and heart failure, compared with no use.
The population-based matched cohort study was conducted between 1998 and 2018 in adults aged 50 years and older who had a diagnosis of dementia at a mean age of 82 years, data on whom were obtained from two Clinical Practice Research Datalink (CPRD) databases in England, namely GOLD and Aurum.
Of the 173,910 identified patients (63% women), 35,339 were prescribed an antipsychotic and were matched using incidence density sampling with up to 15 patients diagnosed with dementia at the same time but who were not prescribed antipsychotics.
In the majority (74.7%) of cases, an atypical antipsychotic was prescribed, most often risperidone (29.8%), quetiapine (28.7%), haloperidol (10.5%), or olanzapine (8.8%).
Mok and colleagues found that the risk for adverse outcomes was highest with current use of antipsychotics (within 90 days of prescription) versus no use, with the greatest risk being for pneumonia (hazard ratio [HR]=2.19). This was followed by acute kidney injury (HR=1.72), venous thromboembolism (HR=1.62), stroke (HR=1.61), fracture (HR=1.43), myocardial infarction (HR=1.28), and heart failure (HR=1.27). However, there was no increased risk for ventricular arrhythmia.
The researchers note that “for almost all outcomes, relative hazards were highest in the first seven days after initiation of antipsychotic treatment.”
Cumulative 90-day incidences were highest for pneumonia (4.48 vs 1.49%), fracture (1.88 vs 1.42%), stroke (1.74 vs 1.04%), and acute kidney injury (1.46 vs 0.74%).
And in terms of numbers needed to harm with antipsychotic use, the investigators report that this figure ranged from nine for pneumonia to 167 for myocardial infarction during the first 180 days after starting antipsychotics, and from 15 to 254, respectively, after 2 years.
Mok and team also considered the type of antipsychotic prescribed, finding that the risks for all outcomes except venous thromboembolism were greater with typical than atypical antipsychotic use.
In a related editorial, Raya Elfadel Kheirbek and Cristina LaFon, both from the University of Maryland School of Medicine in Baltimore, USA, say: “By distinguishing between typical and atypical antipsychotic agents and detailing drug-specific risks, the findings of this study will equip healthcare professionals with more nuanced data to help guide personalized treatment decisions.”
Despite the paucity of alternative treatment options for behavioral and psychological symptoms in patients with dementia, the editorialists advocate for “careful justification of antipsychotic use in dementia care, including a comprehensive assessment of the benefits weighed against a broader range of serious harms than previously acknowledged.”
They add: “Duration of treatment should be minimized, the need for treatment should be regularly reassessed, non-drug options should be explored first and guidelines should be updated to reflect the wider spectrum of risks associated with antipsychotics.”
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BMJ 2024; doi:10.1136/ bmj-2023-076268
BMJ 2024; doi:10.1136/ bmj.q819