Antipsychotic use in people with dementia is associated with higher risks of a wide range of serious health outcomes compared with non-use, according to a new study from a collaboration across the Universities of Manchester, Nottingham, Edinburgh and Dundee.
The findings show a considerably wider range of harms associated with antipsychotic use in people with dementia than previously acknowledged in regulatory alerts, with risks highest soon after starting the drugs, underscoring the need for increased caution in the early stages of treatment.
Despite safety concerns, antipsychotics continue to be widely prescribed for behavioral and psychological symptoms of dementia such as apathy, depression, aggression, anxiety, irritability, delirium, and psychosis.
To address the uncertainty around the risks of antipsychotic use in dementia, researchers investigated the risks of several adverse outcomes potentially associated with antipsychotic use in people with dementia. The outcomes of interest were stroke, major blood clots (venous thromboembolism), heart attack (myocardial infarction), heart failure, irregular heart rhythm (ventricular arrhythmia), fractures, pneumonia, and acute kidney injury.
Using linked primary care, hospital, and mortality data in England, they identified 173,910 people (63% women) diagnosed with dementia at an average age of 82 between January 1998 and May 2018 who had not been prescribed an antipsychotic in the year before their diagnosis. Each of the 35,339 patients 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 used antipsychotics.
Potentially influential factors including personal patient characteristics, lifestyle, pre-existing medical conditions, and prescribed drugs were also taken into account.
Compared with non-use, antipsychotics were 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% vs 1.49% for non-users. At one year, this rose to 10.41% for antipsychotic users vs 5.63% for non-users. 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 non-users.
For almost all outcomes, risks were highest during the first week of antipsychotic treatment, particularly for pneumonia. The researchers estimate that over the first six months of treatment, antipsychotic use might be associated with one additional case of pneumonia for every 9 patients treated, and one additional heart attack for every 167 patients treated. At two years, there might be one additional case of pneumonia for every 15 patients treated, and one additional heart attack for every 254 patients treated.
This was a large analysis based on reliable health data. However, because it was an observational study, no firm conclusions can be drawn about cause and effect. And although a range of factors have been adjusted for, the possibility that other unmeasured variables may have affected the results can’t be ruled out.
With the number of people living with dementia forecast to increase greatly in the coming years, further research into safer drug and more efficacious non-drug treatments for behavioral and psychological symptoms of dementia are needed.
