NeuroVoices: Aaron Ritter, MD, on Navigating Treatment Options for Parkinson Disease Psychosis

Aaron Ritter, MD

Earlier this year, in collaboration with the PMD Alliance, Aaron Ritter, MD, and Kelly Papesh, DNP, put on an educational course for clinicians on the safety and efficacy of pimavanserin (Nuplazid; Acadia) and atypical antipsychotics in the management of Parkinson disease (PD) psychosis. Pimavanserin, approved in 2016, is the only medication that has a label specific for PD psychosis, while other therapeutics are used off-label. The free course included 1.5 hours of video content, 18 lessons, with credits available for attendees.

Set to expire in January 2025, the course covers the treatment landscape for PD psychosis, including the new research on safety and risks of off-label therapies. Designed for a range of clinicians, from movement disorder specialists, neurologists, advanced practice providers, and others, the course will also help medical professionals in the identification of patients to be treated for PD psychosis and how to properly educate them on treatment options. Lastly, the course aims to incorporate the best evidence-based guidelines into standard practice.

As part of a new iteration of NeuroVoices, Ritter, director of the Memory & Cognitive Disorders Clinic at Hoag Neuroscience Institute, provided perspective on the recently launched program. He discussed some of the main educational goals clinicians can expect to achieve, the need to discuss atypical antipsychotics and their effects, and what pimavanserin has done for the management of PD psychosis.

NeurologyLive: Can you provide an overview of your educational session?

Aaron Ritter, MD: Parkinson disease is the second most common neurodegenerative disorder after Alzheimer disease. It's a very common disease that we often see in the community, especially in individuals over the age of 65. One of the most difficult and sort of devastating symptom that comes with Parkinson disease is psychosis, often in the form of hallucinations or in delusions. The treatment for those symptoms can be very challenging, they can have a lot of side effects. Psychosis is one of the main reasons why people become institutionalized and have to go to a supported living system with Parkinson disease. Having options to treat that symptom without causing a lot of side effects—most of the medications that treat psychosis block dopamine—and so that causes quite a conundrum when treating patients with psychosis in Parkinson disease. The recent presentation is about: from a patient perspective, how do we approach this issue? What are our tools that are available to us? We go through a bunch of cases that a clinician may be presented with and think about how we might manage this common and very difficult symptom?

Since pimavanserin was approved in 2016, how has our understanding of how to treat PD psychosis improved?

One of the advantages of pimavanserin is it doesn't block dopamine receptors, it's very specific for serotonergic receptors. It was kind of developed specifically for the issue of visual hallucinations, so it’s a fascinating developmental story. But what we found over time is that it's likely safer than the typical treatments that have been used historically. Most commonly, quetiapine, is associated with a lot of sedation, increased risk of falls, hospitalization. It seems that that since its approval with more data, pimavanserin seems to be a safer option for individuals experiencing psychosis and Parkinson disease.

With the negative effects seen from some atypical antipsychotics like quetiapine, should we be rethinking which off-label therapies we use?

It’s a challenge anytime we were faced with psychosis, especially in the context of Parkinson disease. Most folks will have been on pretty complicated treatment regimens, particularly with dopamine promoting agents for decades. Some of them and may develop acute sensitivity to dopamine blocking agents. It's really kind of a patient-by-patient specific issue, which is really complicated. That's kind of why we felt like there was a need to have a patient approach to this complicated issue.

Quetiapine tends to be safe, as long as we're using low doses. We have to be very careful about the risk for falls, careful for looking at those with high risk for orthostatic hypotension. The cognitive issue is huge as well. There's a lot you need to pay attention to with quetiapine. Pimavanserin tends to be a little bit safer. The cost of pimavanserin and the availability of the drug is not necessarily feasible for all patients. The other thing is, clinicians should spend some time talking to the patient and the family about whether the hallucinations need to be treated. Sometimes individuals may have hallucinations that are not bothersome, or they're infrequent. They may not require treatment where there's a higher risk/reward benefit. That risk/reward ratio needs to be taken into consideration.

A final point is, the cholinesterase inhibitors that are often used in conditions like Alzheimer disease, there may be a role for them in reducing the frequency of visual hallucinations is well. That's off label, but we address that during that talk. If you're interested, I encourage folks to take a look at that CME.

What are some of the challenges with drug development for this condition?

It's incredibly difficult to conduct trials for sort of what label the neuropsychiatric symptoms that come with dementia. First, because many patients are sick at the time that they're experiencing these symptoms. It’s hard to obtain [data]. There are challenges around obtaining consent, there's sort of ethical issues about putting the individuals on placebos when they're having severe symptoms. It's a very challenging clinical trial to run. There's been some good ones over the past 5 to 10 years that have been run primarily in certain centers that are good at running studies like this.

But in general, they are challenging studies to conduct and there tends to be a lot of side effects because it's a frail population that is experiencing a lot of a lot of problems at baseline. They're not easy studies to run. Also, the nature of psychosis in Parkinson disease fluctuates, so it might not be capturing symptoms at each time. In my experience, it's primarily because it is a symptom that we want to treat and to be able to run a placebo-controlled clinical trial, but it's challenging.

Transcript edited for clarity. Click here for more iterations of NeuroVoices.

To register to view the PMD Alliance CME course, "There is No Algorithm: Safety and Efficacy of Pimavanserin and Atypical Antipsychotics in the Management of Parkinson’s Disease Psychosis (PDP)," click the button below.