Now under review, the drug pimavanserin may become the first FDA-approved treatment for dementia-related psychosis.
Roughly 2.4 million Americans experience symptoms of dementia-related psychosis, ranging from visual and auditory hallucinations, to paranoid delusions and mistrust of loved ones. While the burden for families and their loved ones can be immense, there is currently no FDA-approved treatment for symptoms linked to dementia-related psychosis, and the off-label antipsychotics that clinicians may prescribe carry significant health risks for older adults with dementia.
However, scientists are inching closer toward developing a safer and more effective drug. In 2016, ACADIA Pharmaceuticals’ pimavanserin, marketed as Nuplazid, was approved by the FDA as the first and only treatment for psychosis linked to Parkinson’s. Now, pimavanserin is under review by the FDA for treating the symptoms of dementia-related psychosis, and a decision is expected by April.
According to the Director of Banner Alzheimer’s Institute Dr. Pierre Tariot, who was a paid consultant with ACADIA in the research of pimavanserin, there is a huge unmet need for an effective treatment of the hallucinations and delusions of dementia: As many as half of people with dementia experience psychotic episodes.
“At some point in the course of somebody’s dementia, there’s virtually 100 percent probability that they will experience significant and distressing neuropsychiatric signs and symptoms, so in other words, [there is a] 100 percent lifetime risk in the course of the illness.” Tariot told Being Patient. “And among those, psychotic features — that is to say delusions and/or hallucinations — loom large [in over] 40 to 50 percent or so of those folks.”
To assess the effectiveness of pimavanserin in preventing the relapse of psychosis symptoms related to dementia, ACADIA launched the Phase 3 HARMONY trial of pimavanserin in 2017. The study enrolled 392 patients with dementia, including those who had Alzheimer’s, Lewy body dementia, Parkinson’s disease dementia, vascular dementia and frontotemporal dementia.
ACADIA reported that pimavanserin significantly reduced the risk of relapse into psychosis by almost 3-fold compared to placebo. It had no negative impacts on patients’ cognition or motor functions, and the side effects often associated with antipsychotics were infrequent.
Tariot, who was the chair of an independent committee that evaluated whether patients met the primary outcome of the study, said most of the current antipsychotics block receptors in a neurotransmitter system known as the dopaminergic system, as well as receptors in other neurotransmitter systems. He noted that the blockade of these receptors is linked with a host of side effects including impaired movement and cognition, falls and sedation.
On the other hand, pimavanserin targets the neurotransmitter known as serotonin, binding onto and blocking a specific receptor of the chemical messenger.
“It was really tailor-made initially for Parkinson’s patients, because it hits a chemical pathway in the brain that doesn’t affect motor symptoms,” ACADIA Executive Director Dr. Erin Foff told Being Patient in a recent interview. “That makes it particularly useful in a Parkinson’s population when [they] already have motor problems, and many of the other antipsychotic have this liability of causing movement problems.”
She added, “That clued us in that maybe the drug would work very well in a broader dementia population, and that’s what we’ve been studying.”
Now, ACADIA is pressing forward as studies are underway to investigate whether pimavanserin could help treat psychological symptoms related to neurodegenerative diseases, as well as conditions like schizophrenia and major depressive disorder.
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