Studies supports Nuplazid’s safety in older Parkinson’s psychosis patients
Few serious events noted among 595 treated for a year, better sleep seen overall
Two studies support the safety and tolerability of Nuplazid (pimavanserin) in older or frail adults with psychosis associated with Parkinson’s disease.
Safety data on Nuplazid, the only medication approved by the U.S. Food and Drug Administration (FDA) to treat Parkinson’s-associated psychosis, were presented at this year’s International Congress of Parkinson’s Disease and Movement Disorders, recently held in Philadelphia.
“These data inform the clinical use of pimavanserin, which is the only FDA-approved treatment for hallucinations and delusions associated with Parkinson’s disease psychosis,” Victor Abler, vice president of medical affairs at Acadia Pharmaceuticals, the company that markets the therapy, said in an email response to Parkinson’s News Today.
Nuplazid, unlike atypical antipsychotics, does not affect dopamine activity
People with Parkinson’s can experience a range of nonmotor disease symptoms, including psychosis — seeing or hearing things that aren’t real (hallucinations), or false beliefs not based on reality (delusions).
Psychosis is treated with antipsychotic medications, normally atypical antipsychotics, which are second-generation therapies designed to cause fewer motor-related side effects than typical antipsychotics.
However, because most antipsychotics modulate the activity of dopamine, which is abnormally low in Parkinson’s patients, these medications can worsen disease symptoms, particularly in elderly or frail patients. These include bradykinesia or slowed movements, tremors, problems with balance and gait, and sleepiness (somnolence).
“These patients are highly sensitive to the limiting adverse events of atypical antipsychotics, such as somnolence, extrapyramidal symptoms [motor symptoms or movement disorders], tremor, and falls,” Abler noted.
In contrast to atypical antipsychotics, Nuplazid works by targeting serotonin receptors called 5HT2A and does not affect dopamine activity.
Acadia sponsored a global and placebo-controlled Phase 3b clinical trial (NCT03575052) to test the safety and tolerability of Nuplazid in 730 men and women, ages 60 and older, with psychosis (with or without dementia) associated with Parkinson’s, as well as dementia associated with other neurodegenerative diseases. Participants were randomly assigned to oral Nuplazid (34 mg, two 17 mg tablets) or two placebo tablets taken once daily for eight weeks.
Based on findings published in the Journal of Alzheimer’s Disease, Nuplazid was well tolerated and not associated with motor or cognitive impairment. A similar number of adults given either Nuplazid or a placebo experienced one or more treatment-emergent adverse events (30.4% vs. 29.3%) or a serious event (2% vs. 1.5%).
The most frequently reported treatment-emergent adverse events (TEAEs) with Nuplazid or a placebo were urinary tract infections (6.4% vs.4.1%) and headache (2.0% vs. 3.8%).
Fewer than 7% of 595 patients starting year of Nuplazid’s use left study early
Those who completed the eight-week main trial were invited to join its open-label extension (OLE) study, and either continue or start on daily treatment with Nuplazid for about one year.
The study reporting OLE data, “Pimavanserin Safety in Adult and Elderly Patients With Neuropsychiatric Symptoms Related to Neurodegenerative Disease: an Open-Label Extension Study,” was presented at the 2024 conference. Its researchers noted that 452 (76%) of the 595 patients who entered the OLE completed its entire year. During this period, 40% of patients (238 people) on Nuplazid experienced an adverse event, and 6.2% (37 people) had a serious TEAE. Such events led to study discontinuation in 6.6% of OLE patients (39 people), and 11 patients (1.8%, or 11 people) experienced a TEAE leading to death, which was not considered to be related to treatment with Nuplazid.
One patient (0.2% of the 595 in the OLE) had a serious adverse event that investigators thought related to Nuplazid’s use.
In the second study presented, “Safety of Pimavanserin for Parkinson’s Disease Psychosis: Exploratory Analysis of Sedation and Sleep Data From Clinical Studies,” researchers collected safety data from multiple studies into Nuplazid with outcome measures related to sleep and sedation.
Better nighttime sleep, including deep sleep, reported in treated patients
In one study, assessment scores related to sleepiness and poor sleep were similar between patients given Nuplazid and a placebo. Another study showed Nuplazid was associated with better sleep measures at night but not in the daytime, with similar adverse events reported in treatment and placebo groups. The therapy’s use led to a better duration of slow-wave sleep, also known as deep sleep. Slow-wave sleep is considered to support immune system health and memory, and be a sign of good sleep quality in healthy individuals.
Study findings “suggest that pimavanserin may be associated with low levels of sedation and other sleep-related adverse events as well as improvements in nighttime sleep and sleep architecture,” its researchers concluded, recommending further clinical trials.
“The data presented at the International Congress of Parkinson’s Disease and Movement Disorders (MDS 2024) underscore the safety profile of [Nuplazid], particularly in elderly patients with neuropsychiatric symptoms related to neurodegenerative diseases (NDDs), such as hallucination and delusions associated with Parkinson’s disease,” Abler said.
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