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Use of antipsychotics in dementia patients was associated with an increased risk for a wider range of adverse outcomes than previously acknowledged, a population-based matched cohort study from England showed.

In the analysis of more than 170,000 adults with dementia, those prescribed antipsychotics were more than twice as likely to be diagnosed with pneumonia within 90 days as non-users (HR 2.19, 95% CI 2.10-2.28), and increases in risk were seen for nearly all outcomes evaluated:

• Acute kidney injury: HR 1.72 (95% CI 1.61-1.84)
• Venous thromboembolism (VTE): HR 1.62 (95% CI 1.46-1.80)
• Stroke: HR 1.61 (95% CI 1.52-1.71)
• Fracture: HR 1.43 (95% CI 1.35-1.52)
• Myocardial infarction: HR 1.28 (95% CI 1.15-1.42)
• Heart failure: HR 1.27 (95% CI 1.18-1.37)

Relative hazards were highest in the first 7 days of use for nearly all the outcomes. Notably, the risk of pneumonia was nearly 10 times higher in that initial period (HR 9.99, 95% CI 8.78-11.40), researchers led by Pearl Mok, PhD, of Manchester Academic Health Science Center in England, reported in .

Indeed, the number needed to harm (NNH) through 90 days for pneumonia was nine, whereas the next-lowest NNH was stroke, at 29, followed by acute kidney injury at 35. Cumulative incidence of pneumonia at that point reached 4.48% among antipsychotic users versus 1.49% in the matched controls.

"The range of adverse outcomes was wider than previously highlighted in regulatory alerts, which were based on the risks of stroke and death," Mok told 木瓜直播. "Risks for these wide-ranging adverse outcomes need to be considered before prescribing antipsychotic drug treatment to people with dementia."

Antipsychotics are still commonly prescribed to patients with dementia to manage behavioral and psychological symptoms, despite , Mok said. On top of that, the efficacy of antipsychotics for the treatment of those symptoms is limited, she said.

In the U.S., all atypical antipsychotics have carried black box warnings since 2005 over an increased risk of death when used to treat dementia-related psychosis, this was extended to all typical antipsychotics in 2008.

In the study, the risks for all the outcomes noted above were higher with typical versus atypical antipsychotics in the 90 days after a prescription except for VTE and myocardial infarction, where no significant differences were observed.

"Our study shows that it is even more important to take account of risk of harm when considering prescribing these medicines, and to use alternative non-drug approaches wherever possible," Mok said.

In , Raya Elfadel Kheirbek, MD, and Cristina LaFon, BS, both of the University of Maryland School of Medicine in Baltimore, said the findings indeed expand the scope of known risks associated with prescribing antipsychotics in dementia.

"The findings of this study will equip healthcare professionals with more nuanced data to help guide personalized treatment decisions," they wrote, adding that the study highlighted "the need 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."

To conduct the study, the authors collected data from anonymized electronic health records on patients diagnosed with dementia from January 1998 through May 2018 from the Clinical Practice Research Datalink in England. Most patients were women (63%) and had a mean age of 82 years.

In total, 35,339 of the 173,910 included patients were prescribed an antipsychotic drug during the study period. Risperidone (29.8% of all prescriptions) and quetiapine (28.7%) were the most prescribed antipsychotics, followed by haloperidol (10.5%) and olanzapine (8.8%).

Beyond pneumonia, Mok and colleagues found that the risk of adverse outcomes was highest in the first week after initiating any antipsychotic, including for stroke (HR 3.75, 95% CI 3.00-4.69), acute kidney injury (HR 3.79, 95% CI 2.96-4.87), and heart failure (HR 2.85, 95% CI 2.15-3.78).

Through 90 days, the cumulative incidences of other outcomes for those on antipsychotics versus controls were as follows: stroke (1.74% vs 1.04%), acute kidney injury (1.46% vs 0.74%), VTE (0.39% vs 0.26%), myocardial infarction (0.46% vs 0.33%), heart failure (1.15% vs 0.74%), fracture (1.88% vs 1.42%). Significant differences remained for all except heart failure at 1 year as well.

Risks of many adverse outcomes were higher for haloperidol than for quetiapine, including pneumonia (HR 2.53, 95% CI 2.21-2.89) and VTE (HR 1.99, 95% CI 1.33-2.97), the researchers reported.

The study was limited by its observational approach, and by the potential for residual confounders, which they attempted to address by adjusting for a wide range of patient characteristics.

Kheirbek and LaFon noted that the lack of effective nonpharmacological treatment alternatives for behavioral and psychological symptoms of dementia poses a challenge to reducing the use of antipsychotics.

Mok told 木瓜直播 that since the "number of people living with dementia [is] 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."

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