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Antipsychotic drug shows promising results for treatment of dementia-related psychosis

Clinical trial demonstrates reduced delusions and hallucinations without some side effects associated with current treatments

Phoenix (July 21, 2021) - A two-year study of an investigational antipsychotic drug used to treat severe dementia-related delusions and hallucinations found it was more effective than placebo in decreasing the risk of recurring psychosis--without some of the side effects associated with current treatment options, according to a study published today in the New England Journal of Medicine.

“This is not a miracle drug, but these results suggest the potential of a future new therapeutic tool in our toolbox,” said Pierre N. Tariot, MD, Banner Alzheimer’s Institute director and lead author of the study. “Our current options are older antipsychotic drugs, which are just so toxic.”

The clinical trial of the drug, pimavanserin, was conducted between 2017 and 2019 at 101 sites in North America, Europe, and Latin America among patients with dementia who had persistent psychosis whose average age was 75 and who mostly lived at home. It began with a 12-week open-label trial of 351 eligible patients and found that 217, or 61.8 percent, had a sustained reduction of symptoms. The 217 patients who responded positively were then entered into a double-blind, randomized trial over 26 weeks; the primary end point was the time from randomization to relapse of psychosis. A planned interim analysis showed that the hazard ratio for time to relapse was 0.35 (95% confidence interval [CI], 0.17 to 0.73; P = 0.005), that is, patients on pimavanserin were significantly (about 65%) less likely to relapse than patients on placebo, and the trial was stopped early for efficacy. 

Dementia affects more than 40 million people worldwide, including many elderly patients who suffer severe psychoses that debilitate and torment them, as well as their caregivers. Older generations of antipsychotic drugs have limited effectiveness but result in severe adverse reactions including motor function disorders, cognitive impairment, cerebrovascular events, and increased risk of death; many of the same problems have been seen with relatively newer, so-called atypical, antipsychotics. 

Pimavanserin has been approved by the Food and Drug Administration (FDA) since 2016 to treat hallucinations and delusion related specifically to Parkinson’s disease psychosis. The new study tested its safety and efficacy in patients with psychosis associated with dementia due to Alzheimer’s disease, Parkinson’s disease, Lewy body disease, frontotemporal degeneration, or cerebrovascular disease, indications that are not approved by the FDA. 

The initial phase that lasted for 12 weeks identified 217 patients who had a reduction in symptoms of at least 30 percent on standardized assessments for delusions and hallucinations. Those patients were then randomized between pimavanserin or the placebo for 26 more weeks in a trial that was stopped early for positive efficacy results, so that patients receiving placebo were not denied a potential beneficial treatment. Common adverse events included headache, urinary tract infection, and constipation.

“We were gratified to see that a substantial majority of people were helped without decline in their cognition,” Dr. Tariot said. “On a personal note, my mother suffered through Parkinson’s-related dementia and psychosis, and the only way she could be free of terrifying delusions was to be sedated, unsteady, and confused. It was awful. It would have been good for her to have had a different treatment option.”

The study had limitations, the authors noted, partly because stopping the trial because of its efficacy meant that researchers were unable to measure predictors of relapse over a longer term. The study was supported by Acadia Pharmaceuticals Inc. of San Diego, producers of pimavanserin.

Since its inception in 2006, Banner Alzheimer’s Institute (BAI) has sought to find effective Alzheimer’s disease prevention therapies without losing another generation, establish a new model of dementia care for patients and family caregivers, and forge new models of collaboration in biomedical research. It has made groundbreaking contributions to the unusually early detection, tracking, diagnosis and study of Alzheimer’s, and aims to find an effective prevention therapy by 2025. It includes the pioneering Alzheimer’s Prevention Initiative (API), an extensive profile of research studies and clinical trials, comprehensive clinical, family and community service programs, a leading brain imaging research program, and strategic partnerships with numerous public and private research organizations around the world. Learn more at

Banner Alzheimers Institute Banner Health Research

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