Note to our followers: Our nearly 13-year run of daily publication of new content on came to a close at the end of 2018. Publisher Gary Schwitzer and other contributors may post new articles periodically. But all of the 6,000+ articles we have published contain lessons to help you improve your critical thinking about health care interventions. And those will be still be alive on the site for a couple of years.
Read Original Release

FDA release on drug for treating Parkinson’s psychosis lacks some key details

The U.S. Food and Drug Administration today approved Nuplazid (pimavanserin) tablets, the first drug approved to treat hallucinations and delusions associated with psychosis experienced by some people with Parkinson’s disease.

Hallucinations or delusions can occur in as many as 50 percent of patients with Parkinson’s disease at some time during the course of their illness. People who experience them see or hear things that are not there (hallucinations) and/or have false beliefs (delusions). The hallucinations and delusions experienced with Parkinson’s disease are serious symptoms, and can lead to thinking and emotions that are so impaired that the people experiencing them may not relate to loved ones well or take appropriate care of themselves.

“Hallucinations and delusions can be profoundly disturbing and disabling,” said Mitchell Mathis, M.D., director of the Division of Psychiatry Products in the FDA’s Center for Drug Evaluation and Research. “Nuplazid represents an important treatment for people with Parkinson’s disease who experience these symptoms.”

An estimated 50,000 Americans are diagnosed with Parkinson’s disease each year, according to the National Institutes of Health, and about one million Americans have the condition. The neurological disorder typically occurs in people over age 60, when cells in the brain that produce a chemical called dopamine become impaired or die. Dopamine helps transmit signals between the areas of the brain that produce smooth, purposeful movement — like eating, writing and shaving. Early symptoms of the disease are subtle and occur gradually. In some people Parkinson’s disease progresses more quickly than in others. As the disease progresses, the shaking, or tremor, which affects the majority of people with Parkinson’s disease, may begin to interfere with daily activities. Other symptoms may include depression and other emotional changes; hallucinations and delusions; difficulty in swallowing, chewing, and speaking; urinary problems or constipation; skin problems; and sleep disruptions.

The effectiveness of Nuplazid was shown in a six-week clinical trial of 199 participants. Nuplazid was shown to be superior to placebo in decreasing the frequency and/or severity of hallucinations and delusions without worsening the primary motor symptoms of Parkinson’s disease.

As with other atypical antipsychotic drugs, Nuplazid has a Boxed Warning alerting health care professionals about an increased risk of death associated with the use of these drugs to treat older people with dementia-related psychosis. No drug in this class is approved to treat patients with dementia-related psychosis.

In clinical trials, the most common side effects reported by participants taking Nuplazid were: swelling, usually of the ankles, legs, and feet due to the accumulation of excessive fluid in the tissue (peripheral edema); nausea; and abnormal state of mind (confused state).

Nuplazid was granted breakthrough therapy designation for the treatment of hallucinations and delusions associated with Parkinson’s disease. Breakthrough therapy designation is a program designed to expedite the development and review of drugs that are intended to treat a serious condition and where preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapy on a clinically significant endpoint. The drug was also granted a priority review. The FDA’s priority review program provides for an expedited review of drugs that offer a significant improvement in the safety or effectiveness for the treatment, prevention, or diagnosis of a serious condition.

Nuplazid is marketed by Acadia Pharmaceuticals Inc. of San Diego, California.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.

FDA approves first drug to treat hallucinations and delusions associated with Parkinson’s disease

Our Review Summary

Parkinson's diseaseThis news release from the Food and Drug Administration (FDA) announces the agency’s recent approval of a new drug marketed as Nuplazid (pimavanserin) for the treatment of hallucinations and delusions associated with Parkinson’s disease (PD). The release leaves several crucial questions unanswered. We’re not told how much the drug will cost or how significant is the improvement offered by Nuplazid over placebo. A recent article in Stat that summarized an FDA panel’s recommendation to approve the drug, which the FDA followed, found that “In the pivotal trial behind Acadia’s marketing application, Nuplazid showed only modest improvements over placebo, and was tested in a way that makes it difficult to compare against other treatments.”

A public memo from the FDA on Nuplazid seems to suggest for about every two patients who are expected to benefit greatly from Nuplazid, another patient will suffer a significant side effect.

The release provides very little quantitative information but spends a great deal of time explaining the many symptoms of PD.


Why This Matters

About 40 to 50 percent of PD patients experience some form of psychosis, ranging from mild hallucinations to severe paranoid delusions. Medications used to treat PD tremors are considered the top risk factor for developing psychosis. Other risk factors are advanced age and severity of the disease as well as cognitive decline. Because PD patients are at risk of developing new side effects with the addition of new drugs, any news of an improved anti-psychotic with fewer side effects would be welcome news. It’s unclear what the newly approved drug Nuplazid, supposedly developed specifically for PD psychosis, has over existing generic drugs used to reduce or manage psychotic symptoms.


Does the news release adequately discuss the costs of the intervention?

Not Satisfactory

The news release makes no mention of Nuplazid’s cost. An online search for the anticipated cost of the drug revealed only that market analysts predict the drug will reach blockbuster status — meaning it will have sales of at least $1 billion. The drug will no doubt be much costlier than competing generic anti-psychotics.

Does the news release adequately quantify the benefits of the treatment/test/product/procedure?

Not Satisfactory

The release doesn’t quantify any benefits. We’re only told that, compared to a placebo, Nuplazid decreases the frequency and/or severity of hallucinations and delusions. But we aren’t given any actual numbers on how significant this improvement is. There is no information given about the significance of the results.

Does the news release adequately explain/quantify the harms of the intervention?


The release notes that Nuplazid has a “Boxed Warning alerting health care professionals about an increased risk of death associated with the use of these drugs to treat older people with dementia-related psychosis.” Other harms observed in the very brief (6-week) trial are swelling due to the accumulation of excessive fluid in the tissue, nausea  and confusion. The release would have been stronger had it given us an idea of how common or rare these side effects are.

Does the news release seem to grasp the quality of the evidence?

Not Satisfactory

The release states that Nuplazid’s effectiveness was demonstrated in a six-week clinical trial of 199 participants. “Nuplazid was shown to be superior to placebo in decreasing the frequency and/or severity of hallucinations and delusions without worsening the primary motor symptoms of Parkinson’s disease,” according to the release.

The small study size and brief length of the trial are concerns that the release could have called attention to. The FDA has approved many drugs that underwent far more extensive clinical trials that were later pulled from the market due to adverse events. We already noted above under benefits that the release provides little in the way of quantification of the trial results. We are also disappointed that the release didn’t reference where the trial was published in a peer-reviewed journal so that people who wanted to could do an individual assessment of the study results.

Does the news release commit disease-mongering?


The news release doesn’t engage in disease mongering. The release reports that 50,000 new cases of PD are diagnosed each year and that hallucinations or delusions are said to occur in as many as 50 percent of patients with PD at some point during their illness. That’s useful context.

Does the news release identify funding sources & disclose conflicts of interest?


The news release tells us Nuplazid is marketed and funded by Acadia Pharmaceuticals.

Does the news release compare the new approach with existing alternatives?

Not Satisfactory

The only alternative mentioned in the news release is the placebo used for comparison in the clinical trial. What about other treatment methods? According to patient advocacy groups, other government websites and review articles, there are numerous alternatives in use for treating PD-related hallucinations and delusions. Among them, according to the University of Florida College of Medicine:

  • Consider the medication list and consider that medications may be the underlying cause, or contributing to the cause especially pain medications, muscle relaxants, and benzodiazepines (valium, ativan, clonazepam)
  • Consider under the guidance of your doctor a temporary reduction in Parkinson’s treatment medications
  • In some severe cases experts may consider temporarily stopping anticholinergics (trihexyphenidyl, artane, beztropine, benadryl), amantadine, MAO-B inhibitors (selegiline, rasagiline, zelapar, others), entacapone, and even dopamine agonists
  • In some severe case small doses of sinemet or madopar are used to try to gain control of the hallucinations/psychosis, but one must be aware this strategy could worsen Parkinson’s disease symptoms
  • Experts will frequently use dopamine blocking medications such as seroquel or clozaril, but almost never will use other dopamine blockers such as haldol, resperidal, and olanzapine– which all may worsen Parkinson’s symptoms.

Does the news release establish the availability of the treatment/test/product/procedure?


The news release is reporting FDA’s recent approval of Nuplazid so it’s understood the drug isn’t available now. Ideally, for patients’ sake, the news release would have mentioned the company’s announced roll-out plans.

According to a company news release, the firm intends to launch the drug in June 2016.

Does the news release establish the true novelty of the approach?


The news release states that this is the “first drug approved to treat hallucinations and delusions associated with psychosis experienced by some people with Parkinson’s disease.”

Does the news release include unjustifiable, sensational language, including in the quotes of researchers?


There is no evidence of unjustifiable language in the news release.

Total Score: 6 of 10 Satisfactory

Comments (1)

Please note, comments are no longer published through this website. All previously made comments are still archived and available for viewing through select posts.

Susan Molchan

May 11, 2016 at 9:50 pm

Excellent points about the FDA release; it could almost be a release from the company marketing the drug. The medical officer who reviewed the drug put risk/benefit in more detailed perspective:
“you need to treat 91 people for 7 full (therapeutic) responses” while tracking 5 serious adverse events, “one of which will result in death.”