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FDA Reaffirms Safety of Nuplazid® (pimavanserin) to Treat PD Psychosis

The US Food and Drug Administration (FDA) reaffirmed the safety of pimavanserin, known by the brand name Nuplazid®, as being a safe and effective course of treatment for hallucinations and delusions in Parkinson’s disease psychosis (PDP). No new or unexpected safety risks were noted.

In April 2016, the FDA approved pimavanserin, the first targeted medication to treat symptoms of psychosis in adults with Parkinson’s disease (PD). Created by Acadia Pharmaceuticals, this atypical antipsychotic is the first to market to specifically address hallucinations and delusions. An extensive postmarket review concluded that the benefits of the drug continue to outweigh the risks for people who suffer from hallucinations and delusions due to PDP.1,2

Parkinson’s disease psychosis

Parkinson’s disease psychosis is a side effect of mid-to-late stage Parkinson’s and the medications used to treat it.3 Parkinson’s affects each person differently, and not all people with Parkinson’s will develop psychosis.

Defined as a break with reality, PDP is characterized by hallucinations and delusions. Hallucinations are deceptive tricks of the brain on the senses, generally visual in nature. These visions feel real but cannot be seen by anyone other than the person experiencing them. Delusions are beliefs that are not deliberate and cannot be controlled. They are false and fixed.

PDP can be difficult to treat because medications prescribed in the past to reduce the psychological symptoms can worsen the motor symptoms of Parkinson’s. Many people are willing to accept the risks associated with pimavanserin so as to control the psychological manifestations of psychosis.

Risk factors for PD psychosis

There are a number of contributing factors that can bring on PDP. It can develop based on age, medications, disease progression, dementia, sleep disorders, and changes in vision or hearing. The longer a person has the disease (particularly in excess of 20 years), the greater the likelihood that PDP might develop. This is correlated with age, medication, progression, and dementia. There are direct correlations between experiencing hallucinations and delusions, and high levels of dopamine circulating in the brain. This elevation of dopamine is generally related to the medications used to relieve the motor symptoms of Parkinson’s.3

Medications to treat PD symptoms

Certain medications are not safe for Parkinson’s. People with PD know that not all medications are compatible with the drugs used to treat their motor symptoms. Most antipsychotics have traditionally been contraindicated in Parkinson’s. Antipsychotics work by blocking the dopamine receptors in the brain. This results in an exacerbation of the motor symptoms of Parkinson’s.

Nuplazid (pimavanserin) is a selective serotonin inverse agonist, a new type of antipsychotic that works on a novel brain pathway. It targets receptors of the neurotransmitter serotonin, and does not block dopamine like traditional antipsychotics.3 This means it can effectively reduce hallucinations without disrupting motor control. It is distributed through a patient support program and specialty pharmacy network, which increases the likelihood that adverse events, including deaths, will be reported to the manufacturer.

FDA investigation

The FDA did an extensive review because of concerns regarding an increased risk for severe adverse events. The review concluded the benefits of the drug outweigh the risks. The safety profile of the drug was unchanged. No antipsychotic is considered completely safe for treating PDP. Pimavanserin has a boxed warning that warns patients and physicians that using the drug carries an increased risk for death, primarily associated with the treatment of older people with psychosis.4 It is unclear whether these risks are caused by the medication or age and associated illnesses.

FDA recommendations

The FDA recommends continued use of the medication for those that are currently taking it, only as prescribed.2,4 The agency also issued a reminder to physicians that no other antipsychotic medications are approved for the treatment of Parkinson’s disease psychosis. Prescribing patterns were evaluated in the review. These included the concomitant use of other antipsychotics and other drugs that can cause QT prolongation, QT prolongation and serious arrhythmia as well as other side effects associated with pimavanserin, may also be attributed to older age, advanced stage of Parkinson’s disease, and other preexisting medical conditions.

Through the FDA Adverse Event Reporting System (FAERS), the agency will continue to monitor reports of adverse events, data on drug utilization, and safety. Those reports include those reported directly to the FDA, the medication distribution program, and/or those published in medical literature.1,2

  1. Brooks, M. FDA Reaffirms Safety of Pimavanserin in PD Psychosis – Medscape. Published September 21, 2018. Accessed online September 24, 2018.
  2. FDA Issues Statement Reaffirming the Positive Benefit-Risk Profile of NUPLAZID® (pimavanserin) for Patients with Hallucinations and Delusions Associated with Parkinson’s Disease Psychosis. Published September 20, 2018. Accessed online September 26, 2018.
  3. Minton, LS. Pontone,G. Perepezko, K. Psychosis: A Mind Guide to Parkinson’s disease. Parkinson’s Foundation. Updated 2018. Accessed online September 27, 2018.
  4. FDA analysis finds no new or unexpected safety risks associated with Nuplazid (pimavanserin), a medication to treat the hallucinations and delusions of Parkinson’s disease psychosis. FDA website. Published September 20, 2018. Accessed online September 25, 2018.