Sunday, May 10, 2009

Your question: Pagoclone

A reader asked:

Is pagoclone an anti-anxiety drug? Is pagoclone a good medication for the treatment of stuttering? It seems like pagoclone reduces anxiety, which would seem to reduce stuttering (theoretically). So do you like pagoclone as a treatment for stuttering. Take it once daily for the rest of your life and forget about it (vs. other stuff you can do) It this correct: pagoclone reduces anxiety and therefore reduce stuttering, NOT pagoclone reduces stuttering directly... also, side effects like weight gain?


Side effects: The side effects for Pagoclone seem to be mild compared to older medication. I have often read that second-generation medication is not more effective than first-generation medication but it is much more tolerable with mild side effects. Not sure how true it is.

Anti-anxiety: Pagoclone was tested for anti-anxiety disorder but the trials were stopped, likely it was not effective enough. But it might have helped reducing the general anxiety level of normal brain rather than countering anxiety attacks.

Stuttering: We do not know yet, but the current Phase IIb trial will tell us much more. What is already clear is a) it is not going to be a miracle fluency pill b) it will not work for everyone if it works.

pagoclone reduces anxiety and therefore reduce stuttering, NOT pagoclone reduces stuttering directly... We do not know. I tend to think that Pagoclone (if effective) calms the brain and puts it more into a "at home alone" mode which facilitates fluency. But Jerry Maguire disagrees with me and believes that it acts directly on issue. The jury is out there.

So do you like pagoclone as a treatment for stuttering. Take it once daily for the rest of your life and forget about it (vs. other stuff you can do): Here is my view.

8 comments:

Greg said...

Tom--didn't you drop the ball on this one? You never even mentioned the primary theory as to why the drug works. Instead, you're talking about the "calming" effect on the brain? *sigh* Love to see you operationally define that one. *smacks forehead*

Pagoclone modulates (i.e., increases) GABA production, which in turn, lowers Dopamine2 production, thereby allowing our Basal Ganglia Thalamocortical tracts to work with greater effectiveness.

Greg
http://stuttering.me

Tom Weidig said...

OK.

I was just thinking. Well if they test it for anti-anxiety, it is because they had theoretical reasons that it has some inhibitory effects on the brain. So maybe all it does is to slow activity down and calm the brain.

I'll go with the first part, but do we know that it will make this pathway more effective?? Does it not depend on what the optimal D2 level should be. So if it is below, more will make it worse, but if it is above optimal, more might make it more effective??

To be honest, I have not looked at the neurotransmitter stuff in detail, so I keep myself vague... :-)

Tom

Anonymous said...

Thanks a lot!!!

7) Neurologists or other related experts who STUTTER themselves use Pagoclone to treat their own stuttering!!!! :-) This would be strong evidence that Pagoclone is effective and safe. They are professionals and know the realities, and are able to make a much better judgement call than myself.

NEED to know: A neurologist who stutters who is willing to pay his own money for Pagoclone medication?

The issue is: Who Else besides Dr. McGuire is taking Pagoclone. Also, is McGuire considered a real neurologist and does he make money if the trials are successful? (Lots of $$$$$ is involved, meaning I would take a pill and gain weight and deal with all the major/minor side effects...)

What is the cost and benefit of Pagoclone? Cost meaning money and benefits (increased confidence, reduced stuttering, placebo effect, you are doing something for your stuttering, greater public awareness, stuttering is a medical disorder because there is medication for it, and etc, and etc)

JJ said...

Wait, you said: "it will not work for everyone if it works."

Why shouldn't it work for everyone?

============
In theory, it should work for everyone who stutters, right?

Would it work for people with extreme fear of public speaking, or people who tend to be more disfluent in public speaking situations.

Does the pill need to be combined with traditonal speech therapy?

Maybe this would be an easier pill for SLPs to swallow (ex. yes, we recommend the use of Pagoclone for some people, but better in combination with some speech therapy).

Greg said...

Hi Tom,

It's my understanding that Pagoclone essentially works via back-door (i.e., indirect) methodology to regulate dopminergic activity. And I mean to say that it just doesn't blindly result in a lowering of D2 production or uptake across the board, but rather bring it into balance w/ the other neurochemicals in the BGCT. It is predicted to adjust D2 levels relative to each person (if my understanding of the neuromechanism is correct.) And since the 'backdoor' mechanism is indirect, it provides the same end result (D2 regulation) without the side-effects of the drugs using a more direct route toward reduction in D2 production or uptake. Drugs that try to block the uptake of D2 have nasty side effects: see Risperidol or Zyprexa. (I've asked my female grad students if they'd gain 15 pounds to stutter less for years--not a single taker yet!)

If my understanding is incorrect--I hope someone corrects me...

The fact that it may or may not reduce anxiety in some people is just an added bonus. It's ineffective at anxiety reduction relative to the other drugs out there.

From what I gather, Pagoclone was really a drug trying to find a home. It's been around since the early 90s, and has done nothing well and served no real particular purpose. The discovery that it may help stuttering was an accident.

(Much like how they discovered Viagra...which was by accident)

The real 'win' with Pagoclone is that it's a grassroots effort resulting in a paradigmatic shift of how stuttering is to be viewed and treated: as a medical condition.

Tom Weidig said...

JJ:

Why would it not work for all?

a. Evidence shows that pws react differently to the same drugs be it alcohol or someonething else.

b. If there is an imbalance, then it could be too low for some and too high for others. So a drug that only increases or decreases it not going to work for all.

c. Some pws might have more neuro issues and others more learned behavioural / anxiety issues.

d. It is likely that there is not a single cause for stuttering. So it is unlikely one drug can do it all.

And so on.

Tom

Tom Weidig said...

>>>>>Who Else besides Dr. McGuire is taking Pagoclone. Also, is McGuire considered a real neurologist and does he make money if the trials are successful? (Lots of $$$$$ is involved, meaning I would take a pill and gain weight and deal with all the major/minor side effects...)

Jerry Maguire is not taking Pagoclone. I believe that the FDA rules for trial prohibit a main investigator to take the medication that is being tested.

I do not think that he can make directly money with Pagoclone being a sucess, but of course he gains even more in reputation and indirectly makes money through his practise and other consultancy agreements.

Pagoclone is apparently well-tolerated at least over the short-term.

Tom

Jim of Vienna, VA said...

I am in the Pagoclone study and have been in the open label phase for the past two months. During both the double-blind phase and these past two months (the initial portion of the open label phase), my family definitely think my stuttering is worse than before I started on the study. My blocks seem more frequent and the onset harder. I have my next appointment soon and it will be interesting to see if they increase the dosage and if that has any effect either way.