Antipsychotic use in older adults with dementia is associated with a significant increased risk for stroke, myocardial infarction, heart failure, pneumonia, fracture, acute kidney injury, and a range of other health problems compared with nonuse, new research showed.
The adverse events are far broader and pose more severe health risks than previously reported, investigators noted, and suggested greater caution is needed when prescribing antipsychotics to treat psychological symptoms of dementia.
The matched cohort study used patient registry data on nearly 174,000 people with dementia and compared those who were prescribed an antipsychotic on or after their dementia diagnosis with those who had not received a prescription for the drugs.
Any antipsychotic use was associated with double the risk for pneumonia, a 1.7-fold increased risk for acute kidney injury, and 1.6-fold higher odds of venous thromboembolism compared to nonuse.
Investigators found an increased risk for all outcomes studied, except for ventricular arrythmia, and risk was highest for most within the first week of treatment.
“Any potential benefits of antipsychotic treatment therefore need to be weighed against the risk of serious harm across multiple outcomes. Although there may be times when an antipsychotic prescription is the least bad option, clinicians should actively consider the risks, considering patients’ pre-existing comorbidities and living support,” lead investigator Pearl Mok, research fellow at the Centre for Pharmacoepidemiology and Drug Safety, The University of Manchester, Manchester, England, and colleagues wrote.
The findings were published online in The BMJ.
High Risk
Depression, aggression, anxiety, psychosis, and other behavioral and psychological symptoms are common in people with dementia. Despite earlier reports of increased risk for stroke and mortality with antipsychotic use, the drugs are frequently prescribed to treat these symptoms.
While some preliminary studies identified other adverse outcomes from antipsychotic use, results are limited and inconsistent.
Investigators used primary and secondary care data from the Clinical Practice Research Datalink in England. A total of 173,910 adults (63% women) had a dementia diagnosis between January 1998 and May 2018.
Of the total cohort, 35,339 patients were prescribed an antipsychotic on, or after, a dementia diagnosis. Each was matched with up to 15 patients with dementia with no history of antipsychotic use following diagnosis.
Almost 80% of antipsychotic prescriptions were for risperidone, quetiapine, haloperidol, and olanzapine.
Any antipsychotic use was associated with significantly higher risks for pneumonia (hazard ratio [HR], 2.03; 95% CI, 1.96-2.10), acute kidney injury (HR, 1.57; 95% CI, 1.48-1.66), stroke (HR, 1.54; 95% CI, 1.46-1.63), venous thromboembolism (HR, 1.52; 95% CI, 1.38-1.67), fracture (HR, 1.36; 95% CI, 1.30-1.44), myocardial infarction (HR, 1.22; 95% CI, 1.12-1.34), and heart failure (HR, 1.16; 95% CI, 1.09-1.24).
The risk for all conditions was highest within the first 3 months of treatment, with a cumulative incidence of pneumonia among antipsychotic users of 4.48% vs 1.49% among nonusers. At 1 year, this increased to 10.41% for users vs 5.63% for nonusers.
“Given the higher risks of adverse events in the early days after drug initiation, clinical examinations should be taken before, and clinical reviews conducted shortly after, the start of treatment,” the authors wrote. “Our study reaffirms that these drugs should only be prescribed for the shortest period possible.”