Treatment Efficacy for Parkinson Disease-Related Anxiety

Ruth Schneider, MD, assistant professor and director, Huntington’s Disease Society of America Center of Excellence, University of Rochester, discusses her recent research that examined patient outcomes and responses to buspirone in the treatment of anxiety related to Parkinson disease. 

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Welcome back to PopHealth Perspectives, a conversation with the Population Health Learning Network, where we combine expert commentary and exclusive insight into key issues in population health management and more.

Today, we are joined by Dr. Ruth Schneider, assistant professor and director of the Huntington's Disease Society of America Center of Excellence at the University of Rochester. She discusses her recent research that examined patient outcomes and responses to buspirone in the treatment of anxiety related to Parkinson's disease. Dr Schneider?

Hi, everyone. My name is Ruth Schneider. I'm a neurologist and a movement disorder specialist with the University of Rochester in Rochester, New York. I have two main research areas of interest.

One, which is the more relevant one today, is the neuropsychiatric symptoms in Parkinson's disease and other neurodegenerative disorders. Two, the use of novel tools and technologies to identify new disease markers and improve patient care.

What existing data led you and your coinvestigators to conduct your research?

Parkinson's disease is classically described as a motor disease characterized by slowness of movement, tremor, and stiffness, among other symptoms. However, nonmotor symptoms are actually quite common.

These can include cognitive symptoms, autonomic symptoms, like constipation and lightheadedness, and neuropsychiatric symptoms, like anxiety, depression, and psychosis. Anxiety affects approximately 40% of folks with Parkinson's disease and negatively impacts health-related quality of life.

While recognition of anxiety and other nonmotor symptoms has increased, anxiety remains undertreated. On top of that, there is little evidence to guide the appropriate treatment of anxiety in Parkinson's disease. While there are many pharmacologic options for the treatment of anxiety in the general population, these same medications may not be effective in individuals with Parkinson's disease.

We wanted to examine buspirone for the treatment of anxiety in Parkinson's for a couple reasons. One, small early studies showed that it may have some benefit for dyskinesias, which are a common motor complication of Parkinson's disease treatment.

Two, these same early studies suggested that it may cause worsening of motor symptoms. Together, this suggested that we needed more information.

Can you briefly describe the study and its findings, and were any of them particularly surprising?

We enrolled individuals with Parkinson's disease and clinically significant anxiety, without significant cognitive impairment. Participants could be receiving antidepressants or anxiolytics, but we did ask that they remain on stable dosages throughout the study.

Participants were randomized using a four-to-one allocation ratio to either flexible-dosage buspirone or a placebo for 12 weeks. Both participants and investigators were blinded to treatment assignment. The dosage was adjusted by the investigators based on response and tolerability up to a maximum 30 milligrams twice a day.

Our primary outcome was tolerability, which we defined as the proportion of participants who remained on-drug at 12 weeks, but we also looked at a number of secondary outcomes, including a number of different anxiety measures.

We ended up enrolling 21 individuals at our single site. Seventeen were randomized to buspirone and 4 to placebo. Seven participants, all of whom had been randomized to buspirone, discontinued treatment prior to completion of the study. Five participants discontinued treatment due to intolerability.

When we took a little bit of a closer look at this, we found that intolerability tended to occur very early on after treatment initiation. Four of the 5 individuals who discontinued treatment developed symptoms of intolerability within 3 days of treatment initiation.

The most common symptoms of intolerability were worsened motor function and pain. Our median final dosage was only 7.5 milligrams twice a day, which was also our starting dosage. In addition, approximately half of the participants who received buspirone reported an adverse event consistent with worsened motor function.

On the other hand, we did see an improvement on several anxiety measures with treatment with buspirone. Unfortunately, the study wasn't designed to allow for comparisons between a treatment arm and a placebo arm.

We were surprised by the high proportion of participants who were unable to tolerate buspirone. This may have been because this was not a study of buspirone monotherapy. I mentioned before that we allowed people to be on antidepressants or anxiolytics throughout the study.

In fact, 88% of those individuals in the buspirone arm were receiving treatment with an antidepressant or anxiolytic. We were also surprised by the number of participants who reported worsened motor function, particularly a phenomenon called freezing of gait, on relatively low dosages of buspirone.

What are some of the possible real-world applications of these findings in clinical practice?

I think there are a couple takeaways. One, buspirone was not well-tolerated in our small study. However, as I mentioned, most participants were taking an anxiolytic or antidepressant at baseline, and it may be that buspirone monotherapy is well-tolerated.

Second, buspirone was associated with an improvement in anxiety across several measures. However, this was a small single-center study designed to assess tolerability and safety, rather than efficacy. Larger studies are needed to truly inform clinical practice.

Do you and your coinvestigators intend to expand upon this research?

Absolutely. More research is needed to identify the best treatments for anxiety in Parkinson's disease, and more specifically, future research could look at evaluating buspirone monotherapy, identifying predictors of response, or intolerability to buspirone, and to examine other pharmacologic agents.

Then finally, overall, is there anything else you would like to add?

I would simply add that we look forward to helping to identify best practices for the treatment of anxiety in Parkinson's disease. I think this is such an important area of research for Parkinson's, and one that needs more work.

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