WASHINGTON -- The FDA has approved pimavanserin (Nuplazid) for the treatment of hallucinations and delusions associated with psychosis experienced by some people with Parkinson's disease, the agency announced Friday.
Hallucinations or delusions can occur in as many as 50% of patients with Parkinson's disease at some time during the course of their illness, the FDA .
"Hallucinations and delusions can be profoundly disturbing and disabling," , director of the Division of Psychiatry Products in the FDA's Center for Drug Evaluation and Research, said in the release. "Nuplazid represents an important treatment for people with Parkinson's disease who experience these symptoms." It is the first drug approved for this indication, the FDA noted.
In a 6-week clinical trial of 199 participants, Nuplazid was found to be superior to placebo in decreasing the frequency and/or severity of hallucinations and delusions without worsening Parkinson's disease's primary motor symptoms.
The drug has a Boxed Warning advising of an increased mortality risk associated with the use of these drugs to treat older people with dementia-related psychosis, which would be an off-label use.
In clinical trials, the most common side effects reported by participants taking Nuplazid were swelling -- usually of the ankles, legs, and feet -- due to peripheral edema; nausea; and confused state.
In March, an FDA advisory committee voted 12-2 that the benefits of Nuplazid -- which had been granted both a breakthrough therapy designation and expedited review -- outweighed the risks in Parkinson's disease psychosis, although panel members still expressed reservations.
The Psychopharmacologic Drugs Advisory Committee (PDAC) did not make a direct vote on whether or not to recommend approval. However, it did decide that the drug appeared to be efficacious (12-to-2) and that the safety profile was adequately characterized (11-to-3).
Committee chairperson , of the University of Pittsburgh, noted that panelists said that while the pros of the agent outweigh the cons, there are some caveats.
"There were concerns about safety, and an emphasis that the FDA should be as specific as possible in labeling the drug to restrict off-label use," Brent said. "But given the lack of alternatives and the poor quality of life in this condition, I think that explained the majority of endorsements for the favorable risk-benefit ratio."
In terms of alternatives, other antipsychotics such as olanzapine (Zyprexa), quetiapine (Seroquel), and risperidone (Risperdal) are used off-label to treat the condition, but these can block dopamine, which is the most commonly used medication to treat the motor symptoms of Parkinson's disease.
Instead, pimavanserin is a selective serotonin inverse agonist that targets serotonin 5HT2A receptors, so it can reduce the symptoms of hallucinations, delusions, and agitation without adversely impacting the motor symptoms of Parkinson's, the FDA said.