Nuplazid (pimavanserin) for Parkinson’s disease
Fact-checked by What is Nuplazid for Parkinson’s disease?
Nuplazid (pimavanserin) is an oral medication approved to treat hallucinations and delusions in people with psychosis related to Parkinson’s disease.
Parkinson’s disease psychosis — when a person has trouble distinguishing what is real from what isn’t — is one of the possible nonmotor symptoms of the neurodegenerative disease. It is most commonly marked by hallucinations — seeing, hearing, or sensing things that are not there — and/or delusions, which are irrational or illogical beliefs without a basis in reality.
Many antipsychotic medications work by reducing the signaling of the brain chemical dopamine. However, people with Parkinson’s disease are already deficient in dopamine, so these medications could make movement problems and other symptoms worse.
While researchers don’t entirely understand Nuplazid’s mechanism of action, it is thought to reduce activity at 5-HT2A receptors, proteins that interact with the signaling chemical serotonin to regulate mood and perception. Because it does not appreciably affect dopamine receptors, it is expected to reduce psychotic symptoms without worsening Parkinson’s motor symptoms.
Nuplazid is marketed by Acadia Pharmaceuticals. Nuplazid generics are not currently available.
Therapy snapshot
| Brand name | Nuplazid |
| Chemical name | Pimavanserin |
| Usage | Used to treat hallucinations and delusions associated with Parkinson’s disease psychosis |
| Administration | Oral tablets or capsules |
Who can take Nuplazid?
Nuplazid is approved in the U.S. for the treatment of hallucinations and delusions associated with Parkinson’s disease psychosis.
Nuplazid carries a black box warning emphasizing that the medication is not approved for treating dementia-related psychosis unless the hallucinations and delusions are related to Parkinson’s disease. Using the medication in elderly people with dementia-related psychosis increases the risk of death.
The prescribing information for Nuplazid also says that the medication is contraindicated, meaning it should not be used, in people with allergies to Nuplazid or any of its ingredients.
How is Nuplazid administered?
Nuplazid is available as tablets or capsules, both of which are taken by mouth with or without food. The recommended Nuplazid dosage is usually 34 mg (one capsule) once daily, though people taking certain other medications that could interact with Nuplazid may need a lower dose (10 mg; one tablet).
Tablets should be swallowed. Capsules can be swallowed whole or opened, with the contents sprinkled over about one tablespoon of a soft food, such as yogurt or applesauce, immediately before consumption.
Nuplazid in clinical trials
The approval of Nuplazid for Parkinson’s hallucinations and delusions was mainly based on data from a Phase 3 trial (NCT01174004) called ACP-103-020. In the six-week study, 199 participants with Parkinson’s-related psychosis received either Nuplazid or a placebo once daily. Results for ACP-103-020 showed:
- participants who took Nuplazid had a significantly greater reduction in scores on the Scale for Assessment of Positive Symptoms (SAPS-PD) than those who received placebo, indicating an easing of psychosis severity
- reductions in SAPS-PD deepened throughout the course of the trial
- the treatment did not have a negative effect on motor function
An open-label extension study, ACP-103-015 (NCT00550238), included participants from ACP-103-020 and other studies. Data showed that improvements observed in the main trials were sustained with an additional four weeks of Nuplazid.
Nuplazid side effects
The most common side effects of Nuplazid reported in clinical trials included:
- swelling in the legs or arms
- confusion
According to the boxed warning, antipsychotic drugs can increase the risk of death in elderly patients with dementia-related psychosis. Nuplazid should not be used in these patients unless their hallucinations and delusions are related to Parkinson’s disease.
Nuplazid can lead to a heart rhythm abnormality called a prolonged QT interval. It should be avoided by people who have or are at risk of QT prolongation, or who take other medications that can cause similar heart rhythm abnormalities.
Nuplazid may interact with other drugs that influence CYP3A4, an enzyme involved in breaking down Nuplazid in the liver. Patients should tell their care providers about all other medications they are using.
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