Hope for Dementia-Related Psychosis

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In the United States, there are currently no Federal Drug Administration (FDA) approved medications for the treatment of psychosis in Alzheimer disease (AD). This is a problem because approximately 25% to 50% of individuals with AD develop psychosis during their illness, and psychosis worsens AD outcomes.¹

But a recent trial found that pimavanserin reduced psychosis symptoms in patients with AD. According to Rajesh Tampi, MD, MS, DFAPA, Psychiatric Times^TM neuropsychiatry section editor, this research could be ground-breaking because “pimavanserin will be the first drug, if approved, for this indication in the US with an indication for psychosis in AD.”

Pimavanserin could improve patient outcomes significantly. Existing antipsychotic drugs may be effective for treating delusions and hallucinations, but antipsychotics are also associated with increased risk for death, cerebrovascular adverse events, sedation, falls, and pneumonia. Given these concerns, effective and safe pharmacological treatment of psychosis in AD remains a pressing need.

Pimavanserin and Psychosis Symptoms

A literature review of clinical studies on pimavanserin as a treatment for psychosis concluded that “pimavanserin may be a pharmacologic consideration for the treatment of psychosis in AD.”¹ In 2 publications, pimavanserin improved psychotic symptoms in individuals with AD when compared with a placebo after 6 weeks. The authors of the literature review warned that further randomized controlled trials were needed before pimavanserin could be considered a standard treatment.

The Latest Study

In 2020 Acadia Pharmaceuticals Inc. submitted an application to the FDA, asking it to approve pimavanserin for dementia-related psychosis.² A serotonergic agent and selective serotonin (5-HT) 2A receptor inverse agonist, pimavanserin may be able to treat hallucinations and delusions.

Acadia’s study is a Phrase 3 trial that began in 2019. It included 117 study locations, scattered across the US, Europe, and Chile, and enrolled 392 participants with dementia who had suffered from symptoms of psychosis for at least the last 2 months.³ Following a 12-week open-label period, participants who responded were broken into 2 groups for the following 26 weeks, in which 1 received a placebo and the other pimavanserin. The study then followed the patients until they had a relapse, defined by hospitalization as a result of dementia-related psychosis, deterioration of dementia symptoms, withdrawal from the study due to lack of efficacy, or use of another antipsychotic medication. 

Acadia reported that pimavanserin significantly reduced the risk of a relapse. Those on the placebo were 2.8 times more likely to relapse during the study period. Given promising results, they filed a supplemental New Drug Application (sNDA) with the FDA.

Bottom Line

Pimavanserin is already FDA approved for the treatment of hallucinations and delusions in individuals with Parkinson disease psychosis (PDS), but the same symptoms have no standard drug treatment for individuals with dementia-related psychosis. The FDA will likely not render a verdict before April 2021, but clinicians may want to keep this research in mind, as it could be an indication for using pimavanserin in the near future.

1. Srinivasan S, Tampi RR, Balaram K, Kapoor A. Pimavanserin for the treatment of psychosis in Alzheimer's disease: A literature review. World J Psychiatry. 2020;10(7):162-174.

2. Pimavanserin – dementia-related psychosis. News release. Acadia Pharmaceuticals, Inc. Accessed November 9, 2020. https://www.acadia-pharm.com/pipeline/pimavanserin-drp/

3. Pimavanserin. Alzforum: networking for a cure. Updated July 24, 2020. Accessed November 9, 2020. https://www.alzforum.org/therapeutics/pimavanserin