Treatment of Parkinson’s Psychosis with Nuplazid

“At what point do you give up – decide enough is enough? There is only one answer really. Never.” Tabitha Suzuma

“Be proud of your scars. They remind you that you have the will to live.” Paulo Coelho

Précis: ~50% of the people with Parkinson’s develop psychotic tendencies. Treatment of their psychosis can be relatively difficult. However, a new drug named Nuplazid™ was just approved by the FDA specifically designed to treat Parkinson’s psychosis. A brief review follows.

Psychosis in Parkinson’s (Hallucinations and Delusions): Psychosis can occur in ~50% of Parkinson’s patients. The Parkinson’s psychosis typically results in hallucinations (where you see or hear things that are not there) and/or delusions (where you have false beliefs). As one could imagine, hallucinations and delusions would be severe/serious aspects of this disorder.  Parkinson’s psychosis requires treatment because these symptoms are life-altering; they lead to an imbalanced emotional status, and they would disrupt interactions with loved ones and others.

“Severe mental illness like psychosis can lead to a tragedy like this – that people can see things that aren’t real and hear things that aren’t real and believe things that aren’t real, and act in that distorted reality.” Andrea Yates

Antipsychotic Drugs (APD) Typically Target Dopamine Receptors: There are many antipsychotic (neuroleptic) drugs available. Historically, most of these drugs target neurotransmitters that regulate nerve cell communications. Blocking the neurotransmitter dopamine is thought important to managing symptoms of psychosis. Modern pharmacology has not only expanded the drugs available, but many years of research has expanded the ‘targets’ for antipsychotic drugs (ADP).

The usual targets for most APD’s include dopamine receptors, serotonin receptors and other monoamine receptors (see figure below).  Therefore, if you are being treated for both Parkinson’s disease and Parkinson’s psychosis you can immediately see the ‘problem’. You likely take some form/mimic of dopamine to manage the movement disorder; at the same time, you could be blocking dopamine receptors with an APD being used to manage the Parkinson’s psychosis. This would likely create an antagonistic medication/treatment-relationship in managing the disorder.


“He wrote on a piece of paper with his pencil. Psychosis: out of touch with reality. Since then, I have been trying to find out what reality is, so that I can touch it.” Jeanette Winterson

“New-Kid-on-the-Block” (Nuplazid™) to Treat Parkinson’s Psychosis: The US FDA has approved Nuplazid (pimavanserin), the first APD of its kind to treat the hallucinations and delusions associated with Parkinson’s psychosis. Nuplazid is being marketed by Acadia Pharmaceuticals Inc. of San Diego, California (click here for more detailed information about Nuplazid). Nuplazid was given breakthrough therapy designation and priority review by the FDA (click here to read the FDA news release); the goal was to help relieve symptoms in Parkinson’s psychosis.

Unlike other APD’s that have broader target sites, as depicted in the figure above, Nuplazid is a selective inverse agonist that targets 5-HT2 serotonin receptors. What is an ‘inverse agonist’?  A slight diversion into pharmacology says that “an inverse agonist is an agent that binds to the same receptor as an agonist but induces a pharmacological response opposite to that agonist.” (click here to read more). For a visual depiction on how an inverse agonist works as a drug, see the drawing below.


Nuplazid Offers New Hope: Using Nuplazid to treat Parkinson’s psychosis should have no negative impact on motor symptoms that need treatment in Parkinson’s. Michael S. Okun, MD, Medical Director of The National Parkinson Foundation, said last month: “Today’s approval of Nuplazid represents a major paradigm shift in the treatment of Parkinson’s disease psychosis. Through its novel and selective mechanism of action, Nuplazid is a breakthrough treatment that works in a whole new way— treating hallucinations and delusions without blocking dopamine receptors and, therefore, not impairing motor function in Parkinson’s psychosis patients.”  Thus, Nuplazid is both a first step and a new approach for managing the symptoms of Parkinson’s psychosis. Only time will tell if Nuplazid is a hopeful beginning for treating Parkinson’s psychosis.

“If we want to cultivate hopefulness, we have to be willing to be flexible and demonstrate perseverance. Not every goal will look and feel the same. Tolerance for disappointment, determination, and a belief in self are the heart of hope.” Brené Brown

Cover image credit:

Inverse agonist figure credit:


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