Wide range of adverse events in patients with dementia taking antipsychotics

By Rebecca Jenkins

Use of antipsychotic medications in patients with dementia is linked to a wider range of adverse events than previously highlighted in regulatory alerts, research suggests.

Current regulatory warnings when using antipsychotics for the behavioural and psychological symptoms of dementia were based on evidence of increased risks of stroke and death, but evidence for other adverse events was less conclusive, UK researchers wrote in the BMJ.

To address this uncertainty, researchers used linked primary and secondary care data to investigate a range of adverse outcomes potentially associated with antipsychotic use in a large population-based cohort of adults aged 50 years and older with dementia.

The dataset included 173,910 people (63% women) who were given a diagnosis of dementia between 1 January 1998 and 31 May 2018 and who had not been prescribed an antipsychotic in the year before their diagnosis.

Each of the 35,339 adults who were prescribed an antipsychotic on or after the date of their diagnosis was then matched with up to 15 nonusers using incidence density sampling.

The analysis found current antipsychotic use (90 days after a prescription) was associated with elevated risks of pneumonia (hazard ratio [HR], 2.19), 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), compared with nonuse.

‘Increased risks were observed among current and recent users and were highest in the first week after initiation of treatment,’ the researchers wrote.

In the 90 days after a prescription, relative hazards were highest for pneumonia, acute kidney injury, stroke and venous thromboembolism, with increased risks ranging from 1.5-fold for thromboembolism to twofold for pneumonia.

No increased risks were found for ventricular arrhythmia or for the unrelated negative control outcome of appendicitis and cholecystitis combined.

Associate Professor Michael Woodward, Honorary Medical Adviser of Dementia Australia, welcomed the study findings, noting that antipsychotics were widely prescribed for patients with dementia, despite warnings about their adverse effects and advice to use nonpharmacological options first.

‘The drugs tend to be an easier option so they will get used, and they will get used inappropriately – partly because there are not a lot of other options, particularly options that work quickly,’ he told Medicine Today.

Professor Woodward said it was unrealistic to advise clinicians to never use the drugs, but stressed there should be some degree of consent from the patient’s family or the patient themselves when initiating antipsychotics.

‘They should be used in the lowest possible dose for the shortest time possible, they should always be used with nonpharmacological approaches and there should also be constant attempts to deprescribe,’ he said.

Professor Woodward, who is also Director of Aged Care Research at Austin Health, Melbourne, said there were about 1.5 million Australians with some form of neurocognitive disorder and many of them would develop responsive behaviours, such as agitation, irritability and wandering.

Ultimately, clinicians needed safer drugs to treat these symptoms, but in the meantime, there was a need to increase efforts to manage responsive behaviours nonpharmacologically, he said. 

BMJ 2024; 385: e076268.