Research Spotlight: Benzodiazepines Associated with Worse Disease Progression in Progressive Supranuclear Palsy

Anne-Marie Wills, MD, MPH, director of the CurePSP Center of Care at Massachusetts General Hospital and associate professor of Neurology at Harvard Medical School, is the senior author of a new letter in JAMA Neurology, Concomitant Medications for Progressive Supranuclear Palsy.

What Question Were You Investigating with this Study?

We were looking for predictors of disease progression in progressive supranuclear palsy (PSP). We had hoped to find medications that would be associated with a slower disease progression, in order to look for possible interventions/treatments. Instead, we found that one class of medications, benzodiazepines, was associated with strikingly worse disease progression.

What Methods or Approach Did You Use?

This was a secondary analysis of a large multicenter clinical trial in PSP ("a phase 2/3 clinical trial of davunetide in PSP"). This approach has not previously been applied to PSP and other groups have not taken such a large, unbiased approach to looking at potentially disease-modifying medications.

What Were the Results?

In brief, participants in the study who were prescribed benzodiazepines (at any time) experienced a mean worsening on 17.1 points per year (on the PSP Rating Scale) compared to an average of 9.9 points/year in the other participants.

What are the Clinical Implications of This Work?

We feel that this is important to publicize to physicians who are treating this illness, because these medications may be harming patients with PSP. Alternative medications, such as antidepressant medications and zolpidem for insomnia, were not associated with any worsening of the disease.

What are the Next Steps?

We wanted to publicize this finding because we feel that it has a direct clinical impact for people with PSP.

Paper Cited:

Iyer, J. M., Gunzler, D., Lang, A. E., Golbe, L. I., Pantelyat, A., Boxer, A. L., Wills, A. M., & AL-108-231 Study Group (2024). Concomitant Medications for Progressive Supranuclear Palsy: A Secondary Analysis of a Randomized Clinical Trial. JAMA neurology, e235215. Advance online publication. https://doi.org/10.1001/jamaneurol.2023.5215

About the Massachusetts General Hospital

Massachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The Mass General Research Institute conducts the largest hospital-based research program in the nation, with annual research operations of more than $1 billion and comprises more than 9,500 researchers working across more than 30 institutes, centers and departments. MGH is a founding member of the Mass General Brigham healthcare system.