Pimavanserin Safety Reiterated in Independent Study

September 28, 2018

An independent investigation out of UC San Diego has found no statistically significant evidence showing a higher risk of mortality with the therapy compared to quetiapine or combination therapy.

Fatta B. Nahab, MD

Just days after the FDA announced its stance on the safety of pimavanserin (Nuplazid, Acadia Pharmaceuticals) for the treatment of hallucinations and delusions due to Parkinson disease psychosis, an independent study from researchers at UC San Diego Health has found no statistically significant evidence to the contrary.

The review consisted of 676 qualifying patient cases, and actually revealed a lower mortality percentage for those using pimavanserin in comparison to those using only quetiapine (Seroquel, AstraZeneca) or those using both therapies, although the differences were not statistically significant.1

“This paper is important because pimavanserin has been in the news, and there is considerable debate and concern about its safety,” said coauthor Fatta B. Nahab, MD, associate professor in the Department of Neurosciences at UC San Diego School of Medicine.2 “We wanted to better understand and assess the risks of using pimavanserin within our own patient community, either alone or in combination with other commonly prescribed medications.”

Nahab told NeurologyLive that while prior studies had already identified an increased risk of mortality associated with the use of quetiapine, it has been less clear whether this was a ‘class effect’ and would also be seen with pimavanserin. "In my own practice, I had not had concern about the safety of pimavanserin though the reports in the press did bring to the forefront whether it was safe to use," he said.

The group of researchers examined more than 4,400 anonymous medical records of UC San Diego Health patients with Parkinson disease, identifying more than 600 cases between April 29, 2016, and April 29, 2018. They acknowledged a significantly increased risk of mortality, 74%, in the group of patients using only quetiapine compared to those not on quetiapine monotherapy. Additionally, a trend toward increased risk was also revealed in the combination group.

Although, Nahab noted that it would be “reasonable to assume” that those who require these therapies tend to have greater severity of disease, and thus are at a higher risk of both complications with their medications, as well as mortality.

“Our findings provide the largest comparative report of mortality risk in PDP to date,” said Nahab. “But there were limitations to our study based on its design and nature. We did not find any new or unexpected concerns about the use of pimavanserin in the treatment of PDP, which may provide some reassurance to clinicians, patients, and families. But more work is needed to better evaluate factors like disease severity and cause of death to improve our understanding of the potential risks of treating [Parkinson disease psychosis].”

The concerns about pimavanserin’s safety stemmed from an April 2018 story from CNN,3 which pointed out a lack of extensive clinical review of the therapy and submitted reports of increased adverse events in patients using it, “including deaths, life-threatening incidents, falls, insomnia, nausea, and fatigue,” the story stated.

In a retrospective chart review of the therapy, published in Neurology in April 2018,4 another group of investigators reported that 50 of 59 patients that began treatment with the therapy tolerated it without significant adverse effects. The most common adverse effect was worsening gait instability and weakness, reported in 5 patients. In total, 42 patients reported clinical improvement. Additionally, the authors noted that of the 37 patients who were still taking pimavanserin, 14 were concomitantly taking quetiapine at a median daily dose of 25 mg, and 1 was taking olanzapine. Only 5 of the 20 patients that failed on pimavanserin achieved subsequent symptom improvement on a different antipsychotic medication.

"Based on the data currently available, pimavanserin is a safe option for physicians to use that is specifically indicated for Parkinson’s disease psychosis," Nahab said. "Furthermore, this latest data should help to alleviate concerns by patients and their families about its use. "

REFERENCES

1. Moreno GM, Gandhi R, Lessig SL, Wright B, Litvan I, Nahab FB. Mortality in patients with Parkinson disease psychosis receiving pimavanserin and quetiapine. Neurology. Epub September 26, 2018.

doi

: 10.1212/WNL.0000000000006396.

2. LaFee S. Researchers Evaluate Controversial Treatment for Parkinson’s Disease Psychosis. UC San Diego Health website. health.ucsd.edu/news/releases/Pages/2018-09-26-Researchers-Evaluate-Controversial-Treatment-for-Parkinson%E2%80%99s-Disease-Psychosis.aspx. Published September 26, 2018. Accessed September 27, 2018.

3. Ellis B, Hicken M. FDA worried drug was risky; now reports of deaths spark concern. CNN website. cnn.com/2018/04/09/health/parkinsons-drug-

nuplazid

-invs/index.html. Published April 9, 2018. Accessed September 27, 2018.

4. Sellers J, Darby R, Claassen D. Clinical Experience with Pimavanserin for Treatment of Parkinson’s Disease Psychosis (P1.040). Neurology. 2018;90(15 Suppl).