Wednesday, November 03, 2010

Pagoclone is dead, long live Asenapine?

Ora and Holger sent me this very recent interview with Jerry Maguire.

Maguire seems to have given up on Pagoclone:
A few years back Maguire and his team tested a drug that showed great promise: Pagoclone, the only drug ever designed specifically to help stuttering [ERROR OF AUTHOR], eased anxiety among subjects and helped them speak more fluently, without any major side effects. But it hasn't been approved by the Food and Drug Administration, and it won't be any time soon, Maguire said.
And now he seems to believe in Asenapine:
... and he may have finally found the solution: a drug that's going through a trial at UC Irvine
under his supervision. The medication, which is already in use to help people with bipolar disorder and schizophrenia, is called Asenapine.
"I’ve actually measured it, and before it was 80 perent worse than it is now," said Maguire, who has been on the drug for 8-9 months. "I never even used the phonme I tried to avoid it. Now I’m a professor, and I lecture in front of students, so I’m actually able to get through it. It’s really helped me a ton, and if I were to stop it, after three days my speech would return to where it was."
And more details:
Asenapine inhibits this dopamine-bombardment and seems to give stutterers great improvement. A bonus is that the drug, which is made by Merck, already been approved by the FDA for mental illness. Another bonus is that its side effects -- which could include weight gain and sexual dysfunction -- aren't as severe as with dopamine-blockers that have come before it.
"I think Asenapine is going  to be better" than Pagoclone, said Maguire, who's nearly ready to begin a Phase IV trial for Asenapine at UCI.
We have been here before with Pagoclone. We need to be skeptical again, and wait for serious results. The advantage is that Asenapine is already approved for other disorders. I am a bit confused that it's a Phase IV. I thought that this is a trial for 1000s of users to detect rare side effects.

So what about Pagoclone? The results have not been made public, and the only official note is that one of Endo's website of the discontinuation. This is a brilliant example of the publication and survival bias. That's why we always see the positive research outcomes, because NO-ONE publishes the bad ones. I sincerely hope that Maguire and others are actually publishing the trial outcome. Especially the result of the placebo group should be very interesting, as it provides a base line to any stuttering treatment.

16 comments:

Anonymous said...

My trial doctor told me at my last visit that I was experiencing the placebo effect when I said that I thought pagoclone was definitely improving my ability to speak.
After coming off pagoclone cold turkey for days I had disrupted sleep, felt on edge and suffered a major increase in stuttering. I had to tell myself not to speak for about three days because I was stuttering on every other word.
Things are a little better now but its a great loss for the stuttering community that we will not have pagoclone available. It has zero side effects when your on it. As for Asenapine, if its anything like Zyprexa or abilify it will help your stuttering but make you feel like a zoned out zombie.

John in Virginia said...

what is the typical dosage for saphris for stuttering? I have been taking it (cutting it in half), but I get so zoned out and fall asleep for 12 hours. Personally I didn't notice too much improvement in my stuttering, but maybe I should give it more time. My stuttering seems to be triggered more by anxiety, so I've found much better luck with xanax-type medications.

Interesting that I sent an email to Dr. Maguire about saphris recently, as my own research led me to believe it would be very effective for stuttering.

Ora said...

John in Virginia:

Please let us know if you find out anything further about the drug, particularly if you hear from Dr. Maguire about the recommended dosing.

Anonymous said...

Phase IV starts after drug approval. So it can not be phase IV, they must start testing on small groups first - from phase II.

E.g. check Wikipedia:
http://en.wikipedia.org/wiki/Clinical_trial

Ora said...

Phase IV starts after drug approval. So it can not be phase IV

Asenapine has already been approved and is on the market for certain uses.

I'm not saying I know anything about the Phase IV trial for Asenapine... just that it's not impossible that there are Phase IV trials, since the drug has already been approved for some uses.

John in Virginia said...

I was taking the drug at 2.5mg (cutting the tablet in half) at night, and it knocked me out like I was hit by a baseball bat (so it is not surprising that this drug is also being used off-label for insomnia). I really didn't notice too much improvement in my stuttering, but again I was so groggy perhaps it was a moot point. I may try again at 1/4 of a tablet.

Is it ok to take Asenapine along with an anti-anxiety agent like Celexa?

The other blog that Tom links to above is fabulous by the way. And I agree (just based on discussing with different stutterers) that different stutterers will respond best to different medications. Maybe some need the dopamine antagonists, and some need the GABA medications. I hope the research and the progress continues.

UrbanMermaid said...
This comment has been removed by the author.
Justin said...

Great to read this news, as a lifetime stutterer.

After hearing Jerry speak a couple times at different events, it gives me great hope that he is out there working harder than anyone in my lifetime to find medication for this problem that has devastated my life for many years.

He may not have all the answers, but no one does. He is trying everything to get it done, and honestly reading this article brought a bit of a tear to my eye.

I think we are getting in the right direction with these medications, but this one is not the end-all solution. If it is knocking people out, and causing them to be non-functional human beings, it isn't going to work.

I'm not sure if I'd trade my stuttering for a zombie feeling every day of my life. It just depends on the day I suppose, some days I would kill to be a stutter free zombie!

John in Virginia said...

what I would love to know is this: do the people who were helped the most by pagoclone the same stutterers who are helped the most by the dopamine antagonists? or is it the case that the two very different medications improve the fluency of two separate subgroups of stutterers?

Anonymous said...

This is great news, especially since we dont have to wait several years to test it out. Unlike Pagoclone, its already out on the market, so its not impossible to get your hands on it.

I have a feeling though this will not be as promising as Pagoclone. If I recall correctly, Pagoclone was a mix of anti-axiety drug and GABA, where as Asepanine seems to just be mind-numbing. I hope Im wrong.

Anonymous said...

I participated in a Pagoclone study and my experience was somewhat like that described in the first post. Pagoclone definitely helped my stuttering and being denied it makes my stuttering noticeably worse.

Frankly, I am really annoyed by the gleeful tone you seem to take over the apparent shutting down of Pagoclone.

Gerald Maguire, MD said...

I want to thank Justin for his kind comments. Also, we have not analyzed whether those who responded to pagoclone also responded to dopamine antagonists. The majority of the pagoclone participants had not received trials of dopamine antagonists prior. However, we will learn more in the coming months as many of the pagoclone study participants are seeking treatment at UC Irvine for treatment with other medications. We may very well learn that we have GABA agonist responders, dopamine-antagonist responders, or possibly, a synergistic group response if one were to combine therapies. The stutter-mind-body blog explains such very well.

Ora said...

Hi Dr. Maguire.

I'm glad to hear that you and your colleagues are continuing your search for promising drug therapies.

Can you give us a sense of how you assess efficacy of your treatments, such as asenapine, or other compounds you may be using?

Since a person's severity of stuttering is typically substantially variable over time, how do you separate out this natural variability from the effects of the drugs? To what extent can you determine whether any change in stuttering severity is due to the treatment rather than natural variability over time?

Do you capture data on the progress of your patients which can be generalized beyond your these specific individuals? Do you perform testing using standard testing instruments with quantified results, or do you capture only self-reported change and physician-observed change?

To what extent are you able to track your patients over time? What about your non-local patients, for whom you coordinate treatment with another physician?

I'd be very interested in your comments on these issues.

Best wishes,
Ora

A fellow stutterer said...

I recently found this study published in June 2011 that I believe is part of the trials. Asenapine was tested on three patients and the results seem encouraging despite the limited 'sampling'.

The title is:
Asenapine for the Treatment of Stuttering: An Analysis of Three Cases

Published in: The american journal of psychiatry

Hopefully it gets approved in Canada soon enough...

Anonymous said...

Is there any more news on Asenapine?

Ora said...

To Anonymous, who just asked about Asenapine.... you might be interested in a few links on research by Dr. Gerald Maguire, who was the principal researcher on pagoclone.

Two interviews with Maguire on Stuttertalk:

September 2012 - "Deep Brain Stimulation and Asenapine in Stuttering Treatment with Dr. Gerald Maguire (367)"

http://stuttertalk.com/deep-brain-stimulation-and-asenapine-in-stuttering-treatment-with-dr-gerald-maguire/

November 2014 - Ask Dr. Gerald Maguire about the Medical Treatment of Stuttering (Ep. 485)
-

http://stuttertalk.com/ask-dr-gerald-maguire-the-medical-treatment-of-stuttering-ep-485/

Another page with interesting information - http://www.mnsu.edu/comdis/kuster/TherapyWWW/drugsandstuttering.html

You could also write directly to Dr. Maguire and ask him for an update.

By the way, Maguire was recently named Chairman of the Board of the National Stuttering Association - http://www.westutter.org/board-of-directors/