FDA Updates Label for Psychosis Medication Pimavanserin
Approved in 2016, the newly updated label changes add more clarity to the use of pimavanserin, noting that patients with Parkinson disease with dementia may be eligible for treatment.
Jeffrey Cummings, MD, ScD
According to a new announcement, the FDA has updated the packaging label for pimavanserin (Nuplazid; Acadia Pharmaceuticals), an approved therapy for Parkinson disease psychosis (PDP), to clarify that the medication may be used for patients with PDP with or without dementia.1
Pimavanserin, originally approved in a tablet form, became the first medication marketed for the treatment of hallucinations and delusions associated with psychosis in patients with PD in 2016. With the new updated label, the agency restated in the Clinical Studies section that the phase 3 study that supported its approval included patients with PDP with or without dementia. Although no risk information was changed, the therapy’s boxed warning language was further clarified to include patients with PDP who also have dementia.
"This update makes it clear that NUPLAZID can be prescribed to treat patients with Parkinson’s disease psychosis, with or without dementia,” Jeffrey Cummings, MD, ScD, director of the Chambers-Grundy Center for Transformative Neuroscience, University of Nevada, Las Vegas, said in a statement.1 "As a prescriber, I believe that this clarification to the Boxed Warning language will help healthcare providers better identify appropriate candidates with Parkinson’s disease psychosis for treatment with Nuplazid."
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Pimavanserin, a selective serotonin inverse agonist and antagonist preferentially targeting 5-HT2A receptors, is the only FDA-approved therapy to treat PDP. Among other antipsychotics, pimavanserin has proven to be one of the most effective in treating symptoms of PDP without affecting motor function. Earlier this year, a published meta-analysis of 19 unique studies assessing antipsychotics in patients with PDP showed that pimavanserin (standardized mean differences [SMD], –4.81; 95% CI, –5.39 to –4.24) and clozapine (SMD, –4.25; 95% CI, –5.24 to –3.26) showed the most significant ability to improve symptoms relative to placebo.2
Led by Ismaeel Yunusa, PharmD, PhD, assistant professor, Department of Clinical Pharmacy, University of South Carolina, pimavanserin continued to significantly improve psychotic symptoms, as indicated by scores on Scale for Assessment of Positive Symptoms for Parkinson’s Disease Psychosis/Hallucinations and Delusions. Using the Unified Parkinson’s Disease Rating Scale, study findings showed that clozapine (SMD, –0.69; 95% CI, –1.35 to –0.02), pimavanserin (SMD, –0.01; 95% CI, –0.56 to 0.53), and quetiapine (SMD, 0.00; 95% CI, –0.68 to 0.69) did not impair motor function.
Pimavanserin remains in development for negative symptoms of schizophrenia with top-line results of the phase 3 ADVANCE-2 trial anticipated in Q1 of 2024. In August 2022, the FDA issued its second complete response letter to Acadia for the to expand pimavanserin’s indication as a treatment for patients with Alzheimer disease psychosis, recommending that the company conduct an additional trial to further demonstrate its safety and efficacy. The FDA did note that while the supportive phase 2 AD psychosis Study-019 (NCT02035553) data were significant, they were limited in their interpretability.3
