This article is more than 5 years old. Information may no longer be current.
FDA approves Nuplazid for psychosis in Parkinson’s disease
Click Here to Manage Email Alerts
The FDA recently approved Nuplazid for hallucinations and delusions among individuals with Parkinson’s disease.
Efficacy of Nuplazid (pimavanserin, Acadia Pharmaceuticals Inc.) was indicated in a 6-week clinical trial among 199 participants. Compared with placebo, pimavanserin decreased frequency and severity of hallucinations and delusions without worsening primary motor symptoms of Parkinson’s disease.
The most common side effects were swelling in the ankles, legs and feet due to peripheral edema, nausea and confusion.
Nuplazid has a boxed warning that indicates an increased risk for death associated with use of atypical antipsychotics in older individuals with dementia-related psychosis.
“Hallucinations and delusions can be profoundly disturbing and disabling,” Mitchell Mathis, MD, director of the division of psychiatry products at the FDA’s Center for Drug Evaluation and Research, said in a press release. “Nuplazid represents an important treatment for people with Parkinson’s disease who experience these symptoms.”
Perspective
Back to Top
Henry Nasrallah, MD
This new drug is a completely novel mechanism of action. Nuplazid is an inverse agonist of serotonin 2A receptors, a very different kind of mechanism than all of the antipsychotics that have been discovered in the last 60 years.
People with Parkinson’s disease have already lost most of their dopamine receptors (caused by neurodegeneration) and are extremely sensitive to the side effects that are produced when dopamine receptors are blocked, which exacerbates their Parkinsonian symptoms. In fact, when we treat schizophrenia with the currently available antipsychotics — all of which block dopamine D2 receptors — young, healthy individuals develop movement disorders resembling Parkinson’s Disease. So you can imagine what happens when currently available antipsychotics to persons with Parkinson’s Disease who develop psychosis: their motor symptoms become worse. It’s a very heavy price to get rid of the psychosis in Parkinson’s disease.
Treating psychotic symptoms with Nuplazid is a major paradigm shift. For the first time ever, we finally have a drug that works on psychotic symptoms without blocking dopamine receptors, which was believed, until now, to be absolutely necessary. The dogma over the past 60 years has been dopamine receptors must be blocked to get rid of psychosis. This new drug Nuplazid proves that wrong. You can actually get rid of psychotic symptoms like hallucinations and delusions without blocking dopamine receptors. The biggest beneficiary of that are Parkinson’s Disease patients when they develop psychosis (and up to 50% of them will do so as the disease progresses).
Patients with Parkinson’s disease are extremely sensitive to dopamine receptor blockade, but clinicians have been using them because they had no other choice. They had no option to treat psychosis in Parkinson’s disease except antipsychotics on the market, all of which block dopamine receptors. You can imagine how much worse their Parkinson’s Disease becomes when you block their few remaining dopamine receptors. In fact, Parkinson’s Disease need to increase dopamine to improve their rigidity, tremor and gait problems.
This is why Nuplazid is definitely a major breakthrough because you can now treat the non-motor symptoms of Parkinson’s disease without worsening the motor symptoms.
Click Here to Manage Email Alerts