In December 2019, Acadia Pharmaceuticals Inc. released promising results from a new clinical trial. The results were presented at the 12th Clinical Trials on Alzheimer’s Disease (CTAD) Meeting. The trial, called the HARMONY study, investigated the use of Nuplazid® (pimavanserin) for the treatment of dementia-related psychosis. Nuplazid is currently approved for use in Parkinson’s disease-related psychosis, but not for psychosis related to other forms of dementia.
Although the results were significantly positive, the trial was relatively small. Acadia Pharmaceuticals plans to meet with the FDA in early 2020 to discuss Nuplazid’s use in other forms of dementia-related psychosis. It is unclear if the FDA will require more research in order to approve Nuplazid for this new use.
Although Nuplazid is not a cure for Alzheimer’s or other forms of dementia, it may help improve quality of life by addressing a distressing symptom, dementia-related psychosis. About 30 percent of people living with dementia are thought to have psychosis.
Psychosis refers to having delusions and hallucinations. Delusions are false thoughts or beliefs that are fixed in a person’s mind. A person who is having a delusion may strongly believe someone has stolen from them or is harming them when there is actually nothing going on. Hallucinations are sensations, such as visions or sounds, that are created by the mind but aren’t actually real. An example of a visual hallucination would be seeing someone across the room who isn’t actually there.
Dementia-related psychosis can be incredibly life-altering both for the person with dementia and their caregivers and loved ones. Currently, there are no drugs on the market for treating dementia-related psychosis aside from Nuplazid for Parkinson’s disease.
How does Nuplazid work?
Nuplazid blocks the action of serotonin in certain parts of the brain. It is thought that delusions and hallucinations may be reduced by stopping serotonin signaling in these areas. Nuplazid does not impact other important neurotransmitters, like dopamine or histamine.
What does the research say?
The HARMONY study was a Phase III clinical trial that included nearly 400 people with moderate-to-severe dementia-related psychosis. For the first three months of the study, all participants received Nuplazid. Those who responded at the end of the first three months (over 60 percent) were allowed to continue in the trial. These remaining participants were split into two groups. Half continued to receive Nuplazid, and the other half received a placebo (non-active drug) for the next six months.
The trial was stopped early after it was noticed that Nuplazid was improving symptoms much more than the placebo. Those taking the placebo were more than twice as likely to have worsening psychosis.
Below are some of the overall results from the HARMONY study:
Nuplazid reduced the risk of relapse or worsening of psychosis by almost 3 times compared to placebo
The risk of stopping Nuplazid for any reason was reduced by 2 times
Taking Nuplazid did not lead to worsening cognition from baseline
Taking Nuplazid did not worsen motor symptoms from baseline
There was only a 5 percent increase in adverse effects when taking Nuplazid compared to placebo (and only a 1.2 percent increase in serious adverse effects)
As mentioned, this is a unique, relatively small study, so more research may be needed to determine if Nuplazid will receive FDA approval for the treatment of dementia-related psychosis.
What are the side effects of Nuplazid?
The most common side effects seen with Nuplazid included:
Swelling of the limbs
Issues with walking normally (gait disturbances)
All of these side effects were also seen to a lesser extent in those taking the placebo.
Things to note about Nuplazid
Nuplazid has a boxed warning that elderly people with dementia-related psychosis may be at an increased risk of death. Within the first two years of being on the market for Parkinson’s, hundreds of deaths were reported to the FDA. This prompted the FDA to re-review the safety and efficacy of Nuplazid.
While a high number of deaths may seem scary, it’s important to consider who is taking Nuplazid. Elderly individuals with dementia, psychosis, and other health-related issues are at an increased risk of death regardless of medication history. After considering this and completing an extensive review of the drug, the FDA determined that the benefits of treatment with Nuplazid outweigh the risks. However, as with any drug, each person’s experience may be different. Talking with your doctor about the personal risks and benefits for you or a loved one can help you decide if treatment with Nuplazid is right in your situation.
Some drugs may interfere with the way Nuplazid is broken down in the body. Tell your doctor about any other medications or supplements you are taking before starting Nuplazid. Nuplazid may also change the way the heart beats, leading to an issue called QT prolongation. Individuals with heart arrhythmias (abnormal heart rhythms) or other heart conditions may not be able to take Nuplazid.1,2
Acadia Pharmaceuticals Presents Positive Top-line Results from Pivotal Phase 3 HARMONY Trial of Pimavanserin in Patients with Dementia-Related Psychosis at 12th Clinical Trials on Alzheimer’s Disease (CTAD) Meeting. Business Wire. https://www.businesswire.com/news/home/20191204005956/en/ACADIA-Pharmaceuticals-Presents-Positive-Top-line-Results-Pivotal. Published December 4, 2019. Accessed December 16, 2019.
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. United States Food and Drug Administration. https://www.fda.gov/drugs/drug-safety-and-availability/fda-analysis-finds-no-new-or-unexpected-safety-risks-associated-nuplazid-pimavanserin-medication. Published September 20, 2018. Accessed 12/16/2019.