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Nuplazid’s Mortality Risk Not Different from Seroquel, Combo Treatment, Study Finds

Treatment with Nuplazid (pimavanserin) does not lead to a different mortality risk compared to the antipsychotic medication Seroquel (quetiapine), or to combination treatment with both medications, in patients with Parkinson’s psychosis, according to results from a large study.
The study, “Mortality in patients with Parkinson disease psychosis receiving pimavanserin and quetiapine” was published in the journal Neurology.
In April 2016, Acadia Pharmaceuticals’ Nuplazid became the first therapy approved by the U.S. Food and Drug Administration (FDA) for hallucinations and delusions associated with Parkinson’s psychosis.
However, two years later, a CNN report cited an analysis by the nonprofit Institute for Safe Medication Practices, which found a total of 700 deaths in the FDA’s Adverse Event Reporting System — including 500 among Parkinson’s patients in which Nuplazid was the only therapy likely involved — in the nine months following Nuplazid’s arrival on the market in June 2016.
Now, researchers at University of California San Diego School of Medicine explored the medication’s safety further. “We wanted to better understand and assess the risks of using pimavanserin (Nuplazid) within our own patient community, either alone or in combination with other commonly prescribed medications,” Fatta B. Nahab, MD, the study’s senior author, said in a press release.
Besides Nuplazid, the team focused on Seroquel, a second-generation antipsychotic (SGA), which is often used to treat Parkinson’s psychosis. Results were mixed. Use of Seroquel and other SGAs led to concerns about increased morbidity and mortality in patients with dementia or those with Parkinson’s, prompting an FDA black box warning.
Unlike Seroquel, Nuplazid does not affect dopamine receptors, so it does not interfere with the effectiveness of Parkinson’s treatments for motor symptoms.
The team conducted a retrospective analysis of 4,478 UC San Diego Health patients with Parkinson’s, of whom 676 were being prescribed Nuplazid, Seroquel, or both, between April 29, 2016 and April 29, 2018.
Results showed that patients treated with Nuplazid alone (113 patients, mean age 75.9 years) had a lower mortality percentage when compared to those treated with quetiapine only (505 patients, mean age 75.2 years), or with both compounds (58 patients, mean age 74.1 years ). However, the differences were not statistically significant.
When compared to 784 Parkinson’s patients not on these medications (mean age 80 years), the results revealed a significantly greater risk (74%) of mortality in the Seroquel-only group and a trend toward increased risk in the combination treatment group.
“It’s reasonable to assume, however, that individuals requiring these medications have greater disease severity and are at a higher risk of complications and death,” Nahab noted.
A subset of the patients receiving both medications exhibited the highest rate of mortality, although not statistically different. Importantly, the team noted that the combination therapy’s safety is not yet established, as the pivotal Phase 3 trial of Nuplazid (NCT01174004) excluded individuals on antipsychotics.
“Our findings provide the largest comparative report of mortality risk in [Parkinson’s psychosis],” researchers wrote.
However, Nahab noted limitations on the study’s design and nature, which precluded the determination of cause of death or duration of antipsychotic treatment.
“While the results pertaining to [Nuplazid] provide some reassurance for clinicians, patients, and families, future studies

Source: Parkinson's News Today

Nuplazid and Clozaril Are Most Reliable Parkinson’s Psychosis Therapies, Review Finds

Parkinson's psychosis therapies

The antipsychotics Nuplazid (pimavanserin) and Clozaril (clozapine) are the only therapies shown to improve Parkinson’s disease psychosis (PDP) symptoms without impairing motor function, in double-blind, placebo-controlled clinical trials, according to a review.

The study, “Pharmacological interventions for psychosis in Parkinson’s disease patients,” was published in the journal Expert Opinion on Pharmacotherapy. 

Parkinson’s disease psychosis is a non-motor symptom that causes patients to experience hallucinations and delusions. More than half of Parkinson’s patients will develop psychosis over the course of their disease.

While hallucinations — seeing, hearing, or feeling things that do not exist — are usually harmless, with no associated emotion, delusions — distorted interpretations of reality — are usually paranoid, creating stressful situations.

Researchers believe the risk factors of Parkinson’s disease psychosis include medication, disease duration, dementia, and delirium — a short-term, reversible symptom usually caused by abnormalities in metabolism, medical conditions, or reactions to medication.

In most cases, Parkinson’s-related psychosis is believed to be a side effect of the medication to treat Parkinson’s. For that reason, treatment involving medication reduction, which can result in aggravated motor symptoms, is only performed when psychosis symptoms become a problem for the patient or caregivers.

In his report, the author argues that before doctors evaluate medication reduction, medical conditions — specially infections — that can cause psychosis should be treated, and psychoactive medication — such as antidepressants, pain killers, and anti-anxiety medication — reduced, if possible.

There is no consensus on the order in which Parkinson’s medications may be reduced, or the speed at which they should be reduced. Clinicians must make those decisions based on the specifics of each patient and their reaction to therapy.

After reducing Parkinson’s medication towards lower levels that can be tolerated by patients, doctors may recommend the use of antipsychotic drugs, such as Nuplazid (pimavanserin), Clozaril (clozapine), or Seroquel (quetiapine, or QTP), to balance abnormal chemical levels in the brain.

Nuplazid and Clozaril are the only therapies which have seen their efficacy supported by double-blind, placebo-controlled clinical trials. Both were shown to reduce psychosis symptoms without impairing motor function.

Nuplazid, the only FDA-approved treatment for PDP, takes four to six weeks to show benefits. On the other hand, Clozaril takes only one week to show responses, but requires frequent blood tests, which makes it inconvenient for elderly patients.

These tests are meant to monitor neutropenia, or reduced levels of neutrophils — a type of white blood cell. This adverse event is reported in some patients under Clozaril.

As for Seroquel, double-blind, placebo-controlled clinical trials showed that it does not improve psychotic symptoms in PDP, even though it does not affect motor function. The author noted that, interestingly, despite the non-positive results in those trials, he and other Parkinson’s experts often use it and find it useful to treat PDP.

Two other antipsychotics, Zyprexa (olanzapine) and Melperone, were also subject to trials. However, none showed benefits for psychosis symptoms. And Zyprexa was shown to induce harmful motor effects, making it a therapy to be avoided.

Dementia drugs, such as cholinesterase inhibitors, showed potential improvements in psychosis features, but additional studies are required to confirm those effects.

As of January 2018, the current position of the International Parkinson Disease and Movement Disorders Society on psychosis, which has not yet been updated to include the positive Nuplazid results, recommends Clozaril over Seroquel. Additional clinical trials are needed to clarify the benefits of other antipsychotic drugs to treat PDP.

The author, Joseph H. Friedman of the Department of Neurology, Warren Alpert Medical School, of Brown University, has received research funding from the National Institutes of Health and the Michael J. Fox Foundation.

The post Nuplazid and Clozaril Are Most Reliable Parkinson’s Psychosis Therapies, Review Finds appeared first on Parkinson’s News Today.

Source: Parkinson's News Today