Nuplazid Can Lower Risk of Death for Parkinson’s Psychosis Patients

US study of compares people using Nuplazid, other antipsychotics

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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Mortality rates appear to be lower among people with Parkinson’s disease psychosis (PDP) being treated with Nuplazid (pimavanserin) relative to those using other antipsychotic medications, according to a real-world study in the U.S.

The study, “Mortality in Patients with Parkinson’s Disease-Related Psychosis Treated with Pimavanserin Compared with Other Atypical Antipsychotics: A Cohort Study,” was published in Drug Safety.

The work was conducted largely by researchers at RTI Health Solutions, an independent nonprofit research organization, and it was funded by Acadia Pharmaceuticals, the company that markets Nuplazid.

“We were encouraged by this large, real-world study showing a lower mortality risk in patients with PDP after initiation of [Nuplazid], compared to other atypical antipsychotics,” Ponni Subbiah, MD, Acadia’s senior vice president, global head of medical affairs, and chief medical officer, said in a company press release.

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Psychosis is a frequent Parkinson’s non-motor symptom, defined as hallucinations, mostly visual, and/or delusions, which are fixed beliefs without a basis in observable reality.

Nuplazid, an oral medicine, is currently the only therapy approved in the U.S. specifically for hallucinations and delusions associated with PDP. Other antipsychotic medications commonly have been used off-label to help manage such psychosis.

Researchers conducted a comparative analysis of mortality between people with Parkinson’s disease psychosis on Nuplazid and those treated with other antipsychotics.

They used data collected from Medicare — the government-funded program that provides health insurance to people 65 years and older — between 2016 and 2019, the first few years that Nuplazid was commercially available.

The scientists identified over 20,000 people with PDP: 2,892 who initiated treatment with Nuplazid and 19,083 who started on a different antipsychotic, such as clozapine, quetiapine, risperidone, olanzapine, aripiprazole, or brexpiprazole.

“This sample drawn from US Medicare data should be broadly generalizable to older patients with PDP initiating antipsychotic treatment in the USA,” the team wrote.

Most of these patients (53%) were men, they had a mean age of 80.9, and 30% lived in long-term care or skilled nursing facilities.

Severe simultaneous conditions, or comorbidities, were less common in the Nuplazid group than in the comparator group, while a greater proportion of patients on Nuplazid were on Parkinson’s medications.

Patients were followed for a mean of six months, with deaths reported for 317 Nuplazid-treated patients and 2,880 of those given other therapies.

To reduce the effect of potential influencing factors when comparing mortality between these groups, the researchers conducted propensity score matching, a statistical method aimed at selecting the people in each group with the most similar features.

Differences in mortality risk ‘consistent’ across patient subgroups

The resulting treatment groups, generally matched for demographic and clinical characteristics, consisted of 2,891 Nuplazid-treated PDP patients and 2,891 PDP patients given other antipsychotics.

Here, results showed that patients on Nuplazid had a significantly lower overall mortality risk — by 22% — compared with those on other antipsychotics.

“The largest differences in mortality risk between treatment groups were observed in the first 180 days [about six months] of follow-up,” the researchers wrote.

A sub-analysis that looked only at 652 matched patients residing in long-term care or skilled nursing facilities found similar results, as did other sub-analyses looking at age groups, sex, and dementia status.

“This large study of [Nuplazid] compared with atypical antipsychotic use among patients aged [at least] 65 years with PDP in the USA demonstrated that [Nuplazid] was associated with a lower risk of mortality compared with that for other atypical antipsychotics,” the team wrote.

“This observed association was consistent across subgroups and sensitivity analyses,” they added.

The researchers noted that this study was limited by its reliance on insurance data.

“Information contained in Medicare is recorded for billing purposes rather than for clinical or research purposes,” they wrote, noting that some important information — such as family history, lifestyle habits, and psychosis severity — could not be assessed, and it may have influenced the results.

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