February 21, 2019
Michael Fralick, MD, FRCPC, Brigham and Women’s Hospital, discusses his recent study that examined a medication approved for psuedobulbar affect, which he found was regularly being prescribed to patients with PD and dementia. He explains why these prescribing habits are concerning.
My name is Mike Fralick. I'm a general internist, board certified in Canada and the US. My background is that I have a Master's of Science and I'm completing a PhD.
I'm going to be talking to you briefly about a study that I was a part of, published in January 2019 in the journal JAMA Internal Medicine.
The study's name is a little bit long-winded, but it's "Assessment of Use of Combined Dextromethorphan and Quinidine in Patients with Dementia or Parkinson's Disease After US FDA Approval for Psuedobulbar Affect."
Let me unpack that a little bit for you. Back in 2010, the FDA approved a medication, which it's trade name, or brand name, I should say, is Nuedexta. Nuedexta is a combination of dextromethorphan and quinidine.
Dextromethorphan, you might be familiar with because it's the active ingredient in a lot of over the counter cough syrups. Quinidine is actually a mild anti-arrhythmic medication, but it's being used not because it's an anti-arrhythmic but, instead, because it increases the concentration of dextromethorphan in the blood.
That is the medication. It was approved for the treatment of something called pseudobulbar affect. If you're unfamiliar with what pseudobulbar affect is, it's a condition that is characterized by sudden, often uncontrollable, and often inappropriate episodes of crying or laughing.
It typically can affect people with amyotrophic lateral sclerosis, also known as ALS. Up to 40 percent of patients, as well as patients with multiple sclerosis. About 10 percent of patients with multiple sclerosis can be affected by pseudobulbar affect.
The drug was approved for the treatment of pseudobulbar affect, and mainly studied in patients with ALS or MS. We asked a very simple question. We asked the question, what proportion of prescriptions are being given to patients that have ALS or MS versus patients who have dementia or Parkinson's disease?
What we did is we conducted a study using two databases in the United States. We identified approximately 13,000 patients who had been prescribed this medication. Interestingly, we found that this medication was predominantly prescribed to people who had a history of dementia or Parkinson's disease and very rarely among patients who had MS or ALS.
Over time, more and more patients with dementia were getting it as opposed to patients with ALS or MS. Just to give you some numbers, for example, by 2017 we found that approximately 70 percent of prescriptions were for people who had dementia or Parkinson's disease and maybe 15 percent were for patients who had MS or ALS.
You might be thinking, "So what? What's the big deal here?" There's a few aspects. One very concerning aspect, myself as a general internist, I know that for patients who have dementia or Parkinson's disease you need to be very careful with the medications that you prescribe these individuals. Dextromethorphan, as we know, can have a pretty powerful sedating effect.
I really worry about prescribing this medication to people who have dementia. We've seen some studies where this drug was used in people with dementia or Parkinson's disease and they had much higher rates of falls, as well as infection. That's certainly concerning for me as a general internist.
We also looked at how much money was being spent on this medication by Medicare. What we found is that back in 2011, approximately four million dollars was spent on this medication, which sounds like a lot to me but I appreciate there's lots of money that are spent on medications in the US.
Fast-forward to 2016. Nearly $200 million was spent on this medication. Remember, the active ingredient here is dextromethorphan. That's something that's readily available at most drug stores over the counter.
You can imagine the potential issue here when it comes to the number of dollars that are being spent and whether or not the amount of money being spent really matches the potential benefits for this medication.
A few other aspects of our study, we also found this medication shouldn't really be given to individuals who have a history heart failure or if they're on other medications that are known to prolong the QT. We found that about 15 percent of patients had a history of heart failure and were taking this medication, which is a big no-no.
Then, approximately 40 percent of patients were also on another medication that prolongs their QT interval.
I think those are the main things I wanted to discuss about our study. Just to summarize it, the take home point here is that this medication, known as Nuedexta, was studied primarily in patients who had pseudobulbar affect due to multiple sclerosis or ALS.
What we found is that the real world prescribing of this medication was typically for people who had dementia or Parkinson's disease. That's quite concerning because I worry about these patients being at particularly high risk of adverse events from medications.
Thanks so much for listening. Again, my name is Mike Fralick. I also want to highlight the work of my co-authors, Chana Sacks as well as Aaron Kesselheim, who supervised this work.