Retigabine (Trobalt, Potiga) — General Discussion

[SoulStation]

I was not planning to share the following information in public - and certainly not at this point in time. But I happened to see your post just before heading off to bed, and I thought... why not...

I got a statement today from a professor of pharmacology (and who co-authored a recent research paper on potassium modulators in relation to treating tinnitus - amongst them Trobalt). I wanted to get a formal statement from him so as to understand the mechanism-of-action of Trobalt in suppressing tinnitus (which would be required for the petition for the ATA of the desired Trobalt-study coming from members of this board). Here is what he wrote to me:


The above statement is coming from a professor of pharmacology! I do not wish to name the professor, but it is known who he is to the staff of TinnitusTalk as well as to a few other members of TT (who participated in the discussion).

If I cannot get a professor of pharmacology research to make a statement, how on Earth will I get anyone to make a statement towards the potential efficacy of Trobalt in suppressing tinnitus?

Something to think about.

(And thanks for keeping it "real"...).

Jakob-
I'm not sure what to make of this but thank you for sharing the info as always.
Ben

 

[RaZaH]

I kind of agree with @SoulStation here , we seem to be jumping to all kinds of conclusions.
Yes, it seems to reduce T but if it is not permanent then its hardly worth it.
Now, if the reduction stays ...that is a different story , fact is , we do not know yet.

 

[rtwombly]

@jazz, @RaZaH, it really is too early to say any of this stuff. We've got to stop saying overly positive or overly negative things. We don't know if Retigabine will cure people with tinnitus over one year. We don't really know if the 6 months/1 year marks really make a difference that matters in this way. There could be hundreds of factors we haven't considered when it comes to why different people have responded differently. We don't know if it's chronicity. We don't have enough data. Zimichael, who went through heightened hyperacusis and had no positive effect, has said this several times. Our sample size is too small.

One thing I've noticed is that several people who have had problems with side effects have a history of recreational drug use. Is that the key factor? What about anti-depressant medication? A lot of us have been on those, did that change our brain chemistry so we can't recover?

According to the User Experience thread, we've never had a single woman try Retigabine. Not one. Will women respond better than men? Will they handle the side effects better or worse?

Are Eastern Europeans more prone to bad reactions? Does the country of manufacture matter?

What actually happens when you go above 900mg? Nobody has tried. Maybe 950mg/day cures everybody in a week.

It's too early to draw conclusions. All we can do is make smart decisions for ourselves personally and see where the data leads.

 

[SoulStation]

Maybe 950mg/day cures everybody in a week.

mmm...yes that's it.

 

[RaZaH]

I would think that people with a history of recreational drug use would be more tolerant to the side effects as some of them seem slightly psychadelic ? But I of course have no real idea.

 

[jazz]

We don't have enough data.

Totally agree. I am extrapolating from what I've observed/am observing from the current people taking Retigabine.

We don't know if it's chronicity.

Actually, chronicity is a very important factor in tinnitus. That is well accepted in the medical community. Chronicity is not just about tinnitus. It's about brain diseases and neuroplasticity, evidenced by the old saying "cells that fire together, wire together." (The Hebbian theory.)

What isn't known--and won't be known for a long time--is the correlation between chronicity and the various treatment modalities for tinnitus currently in development or in the future.

In both clinical trials for tinnitus (Autifony; AM 101), tinnitus duration was carefully specified--undoubtedly to insure the best possible results from the trials.

Of course, you raise very important questions about Retigabine regarding its effect and possible interplay among many variables--including gender, individual genetic and physiological differences, and lifestyle choices. But it will take many years to unravel all these variables; and it's is unknown what variables will be considered salient and thus pursued by researchers.

We don't know if Retigabine will cure people with tinnitus over one year.

Totally agree. We really don't know if Retigabine has cured anyone. Mpt has no symptoms, but is he cured? That's not the same thing. Actually, cure is a misleading word to use with tinnitus or any brain disorder. Perhaps, we should just substitute with "symptom free."

Anyway, we are all on the same page here: reading, gathering information, thinking, revising, then gathering more information. It is a tedious process.

 

[cdog]

Mpt has no symptoms, but is he cured? That's not the same thing.

Well, if he has no symptoms, and will continue to have no symptoms, for some time x in the future, then I think we can all agree that fits the definition of the word "cure". The question is what x should be - is it "the rest of his life", is it "five years (as in five year survival rate)" or is it something else? What if, say, tinnitus goes away for 3 years as a result of the retigabine treatment, and then comes back, and is amenable to the same treatment again. I would still classify that as a cure of sorts, in a similar sense to when you get an infection, and a course of antibiotics is a cure...even though you will probably get infected again at some point in your life.

 

[RaZaH]

We need at least one more person with the same results as Mpt before we go all nuts about this drug.
Having said that , I should get this stuff tomorrow. Its always getting delayed but at least all the "legalities" are out of the way.

 

[rtwombly]

We need at least one more person with the same results as Mpt before we go all nuts about this drug.
Having said that , I should get this stuff tomorrow. Its always getting delayed but at least all the "legalities" are out of the way.

Of course you have to realize, I can come on here and be optimistic and cheer everybody on...but so far I have not been able to convince a doctor to let me try for myself. I'm visiting a doctor I didn't convince tomorrow, in fact. He's a good doctor, just doesn't like to mess with dangerous drugs like this, which I can obviously understand.

I'm somewhat jealous, RaZaH, and I wish you the best results possible. I would recommend trying locoyeti's dosing schedule (maybe a little more time between jumps, but he is getting results) and making up your mind ahead of time that you won't be thrown off by the side effects. I don't mean you shouldn't pay them close attention and take action if they seem to be leading to a dangerous condition, just go in expecting to feel bad for awhile and view it as something temporary that you have to do for yourself and get through. I know that sounds simplistic, but I talk to myself a lot like this these days, and it does help. All the time I'm saying to myself, "Ok, this was this kind of day, maybe tomorrow will be different." "This activity didn't feel right to me, maybe something else will work better." Positive self-talk has got me through a lot.

 

[jazz]

Well, if he has no symptoms, and will continue to have no symptoms, for some time x in the future, then I think we can all agree that fits the definition of the word "cure".

Tinnitus does leave a neural signature on our brains. Doctors can see it, and they are able to ascertain the tinnitus intensity, utilizing some characteristics of this signature. (De Ridder does this.) Now, I believe, you can be symptom free, but still have that neural signature. Perhaps, the signature is modified; for example, there are less connections from your auditory mid brain to your prefrontal cortext. But the abnormal activity that originally caused the tinnitus is still (mainly) there. You are just no longer perceiving it.

Is this a cure? For practical purposes, yes. But the injury (neural imprint) is still there, and thus the likelihood of relapse is increased. I would probably think of such a cure as "in remission."

The question is what x should be - is it "the rest of his life", is it "five years (as in five year survival rate)" or is it something else? What if, say, tinnitus goes away for 3 years as a result of the retigabine treatment, and then comes back, and is amenable to the same treatment again

My remission hypothesis answers some of these important questions. But even if you were cured by my standards (no more abnormal activity), it is still likely you will relapse. There are genetic factors at play that predispose someone to tinnitus. And there is also aging, the most common cause of tinnitus.

Would the same treatment work if the tinnitus recurs? I don't know. But I assume it would, unless you've damaged some auditory structure that resulted in total hearing loss. Then, of course, you might get relief through a cochlear implant.

 

[cdog]

Tinnitus does leave a neural signature on our brains. Doctors can see it, and they are able to ascertain the tinnitus intensity, utilizing some characteristics of this signature. (De Ridder does this.) Now, I believe, you can be symptom free, but still have that neural signature.

Can this neural signature be (strongly statistically) correllated with the subjective perception of tinnitus intensity? If so, has there been any study conducted (with a decent sample size) that demonstrated such a correlation? And by correlation I mean both a binary "signature existence correlates with tinnitus existence" one, and/or a spectrum-like "the extent/shape/form of the signature correlates with the tinnitus intensity" one.

Perhaps, the signature is modified; for example, there are less connections from your auditory mid brain to your prefrontal cortext. But the abnormal activity that originally caused the tinnitus is still (mainly) there. You are just no longer perceiving it.

I'm not sure we can say that, given our current knowledge. For example, perhaps Mpt's signature would have been not only modified but completely reverted to normal? Or if not right away, then in time, with the absence of perceivable tinnitus. This would actually make sense, since just as the aberrant behavior leading to the signature developed due to some Hebbian wiring/plasticity that was triggered by the upstream cause of tinnitus (like IHC damage, or DCN), in the same manner we would expect the plasticity to revert its original effects when that cause of tinnitus is removed.

Is this a cure? For practical purposes, yes. But the injury (neural imprint) is still there, and thus the likelihood of relapse is increased. I would probably think of such a cure as "in remission."

Right, as long as one is asymptomatic, I would consider it a cure. That there is some non-functional residual change in the neural wiring is not incredibly important, and is quite common - it would be like someone who is cured of chickenpox as a child still carries the virus inside of them for the rest of their lives. Is the risk of a relapse increased? Perhaps, but like all risls, a 100% increase from a 1% absolute risk is still only 2% absolute risk...

My remission hypothesis answers some of these important questions. But even if you were cured by my standards (no more abnormal activity), it is still likely you will relapse. There are genetic factors at play that predispose someone to tinnitus. And there is also aging, the most common cause of tinnitus.

I think it is a conditional likelihood - where a large part of the condition would be your behavior. If someone takes a cavalier attitude after becoming symptom free and starts attending loud events or concerts, listening to loud headphone music, etc. again, just like before they were first symptomatic, then the likelihood of relapse is greater. But if one learns their lessons and takes proper precautions, then who is to say tinnitus will come back on its own - sans any triggers?

 

[jazz]

Can this neural signature be (strongly statistically) correllated with the subjective perception of tinnitus intensity? If so, has there been any study conducted (with a decent sample size) that demonstrated such a correlation?

I'll check my sources tomorrow and post. Too tired tonight!

And by correlation I mean both a binary "signature existence correlates with tinnitus existence" one, and/or a spectrum-like "the extent/shape/form of the signature correlates with the tinnitus intensity" one.

Yes. I'm not a neuroscientist, of course. But this is how I remember the study. The one I recall was done by De Ridder a few years ago. But there may be more. Over the past two years, I've spent many hours reading about abnormal neural oscillatory activity and tinnitus. It's a subject I'm interested in.

 

[dan]

Dear Jakob, Thank you for your interest in the work. We do not know the mechanism of how retigabine (Trobalt) decreases induced firing of neurons, or whether this activity could suppress symptoms of tinnitus. In light of the known side effects of the drug (blue eyes, skin, tremor, etc) it is not likely to be useful for treating tinnitus, especially long term. Dr. Moore's lab is currently working on potentially more effective alternatives with fewer or no side effects. However, securing funding for this research remains an uphill battle.

....does he know Trobalt's mechanism of action in epilepsy I wonder ?
@attheedgeofscience

 

[attheedgeofscience]

....does he know Trobalt's mechanism of action in epilepsy I wonder ?
@attheedgeofscience

I wouldn't know, and... I do not intend to ask him that question.

But here is what I will say. When I was in contact (twice) with another researcher (at the professor level) and with direct insight of the AUT63 clinical trial, this person also mentioned that basically "it's early days". The person was not suggesting that AUT63 was not going to work, but it simply remains unclear if it will work as intended (in humans), how well, and if it will require life-long treatment or not. Especially, this last point (ie. curative or life-long suppressive treatment) was telling, in my opinion. The fact that "they" do not know if 4 weeks treatment will permanently suppress tinnitus (in humans) means they really do not know that much - at least not empirically. Sure they know a lot, theoretically, but as I have told this board a few times already: in medicine, 1 + 1 ≠ 2.

I have seen several members on this board speculating as to whether Autifony will try to maximize profits by requiring their treatment to be life-long instead of curative. Well, let me tell this board how I see it: with 99% certainty, Autifony does not know the answer to that question themselves - they are just hoping that the thing will actually work in the first place!

And the above is also the reason why you do not see me posting long threads about the theories behind tinnitus, potassium modulators, or how the universe works, for that matter. It's pointless because... we don't know! So why spend time on it?

Basically the professor's statement from yesterday nullifies at least 40-50 pages of this now 93-page thread. Something to think about.

Anyway, I'll see if I can get a statement from GSK. But, I doubt it; pharmas would not have any interest in speaking with the likes of me - because it is of no business value to them to start releasing information on their own product. So I doubt I will get very far.

 

[attheedgeofscience]

What actually happens when you go above 900mg? Nobody has tried.

Agreed.

However, I would... ahem... prefer to leave that "pioneering opportunity" to someone else than myself. Any takers?

 

[dan]

@attheedgeofscience , yes I totally understand what you are saying about AUT63. Indeed, I posted several emails I received from their CMO, in which he basically said the exact same thing that you just stated -
Autifony does not know about efficacy of aut63 in humans at all- they only know what they know from animal model experiments.

What I find strange is that your source stated, I quote-
"We do not know the mechanism of how retigabine (Trobalt) decreases induced firing of neurons..."
When in fact we do know some things about the mechanism of retigabine.
c/o Dr. C. Large paper on retigabine, c/o benryu TT explanation of interspike modulation.

 

[valeri]

Then what on earth was the science behind trobalt in the first place????
Sure it didn't randomly come out of housewives kitchen

 

[amandine]

@valeri
@dan

well done valerii Common sense comment!
Of course they know more than they have said in their response emails. As you said, they didnt just pick it up and say ''oh this is a nice colour, we ll try this one on lots of rats and then try it on a few people after that'.

 

[valeri]

Well all I can say is that just because someone has some fancy title attached to his/her name doesn't necessarily mean their knowledge and expertise lives up to it.

Response from the above mentioned person is pure BS.

 

[Danny Boy]

Well all I can say is that just because someone has some fancy title attached to his/her name doesn't necessarily mean their knowledge and expertise lives up to it.

Response from the above mentioned person is pure BS.

To be honest...They still don't know how 'The Pill', morning after pill, works. If it's the same for trobalt, then I can very well believe it.

 

[Juan Carlos]

Ok, i feel the need to make a little resume now, there is too much mess in this thread. we have here minly 3 concerns here

1. Is RTG effective to treat Tinnitus?. YES. No matter what any doctors says a this point, we have huge evidence of around 90% of tralees (no way of placebo) and scientific base wich has been explained in scientic documents shared among this thread
   
2. Is the cure permanent?. WE DONT KNOW. too few trialees followed the plan, actually mpt and christian only? N sample is too small
3. SIDE EFFECTS: Why is everybody so scared about side effects basing on the experience of barely 10 people, when there is a serious study of 1365 people ?

None of the 1365 people is dead or had any serious issue, why should be a trialee be scared?
The only big concern IMO should be the Retina pigmentation, that happened only in cases of more than 3 years and nobody know if its reversible. Its recommanded to everyone to make eye examination, I will do so

About the kidney, its very strange, none of the 1365 wich taked for very long term reported problems and suddently here appears a guy with kidney problems, we dont really know if that is attached to Potiga. when was the last time he checked the kidney @Ricardo ? that very strange, could you be one of the 0.00XX% affected?
Are you worried about this? very easy, do urine and blood exams, explain everything to your GP, he dont know a shit about Tinnitus but he can help you with this

About psycho-effects: thats it, we all know, its a known side effect, are you surprised to feel drunk after Tequila? . Enjoy them. If the concern is about the job, I do this: change the dosage schedule: take dose at 20h,4am and 12am. If 12am hit you hard at job, take a bit lower and bigger on the others. At 20h a normal day i finished my job and sport and im safely at home ready to cook, at 4am just wake up, take pill and sleep again. That effect hits after 1-3h after taking the pill

Its a personal choice of everyone to start treatment and you won't know if side effects are bereable until you try. It could be a high price but the potential reward is huge

I hope i wont eat my words. all the best

 

[attheedgeofscience]

Then what on earth was the science behind trobalt in the first place????

What "science"...?

Specifically, what "science" in relation to Trobalt, tinnitus, and humans?

There is a difference between anecdotal evidence and "science". Don't get me wrong, I think anecdotal evidence can be very important. It can provide the starting point for a much larger investigation. Great! But that's not science.

Now, I am sorry to potentially be the party breaker here, but I only engaged in the dialogue with the professor of pharmacology because of your own request for a petition, and because @Dr. Nagler politely "tasked" me with the job of writing a description of the mechanism-of-action of Trobalt in relation to tinnitus. Being the competent person I am, I immediately realized that it would not be prudent for a "finance person" to write such a mechanism-of-action. And certainly not for a formal petition requesting a study on humans, no less! So what did I do? I decided to attempt to get a written statement from the best of the best - a professor of pharmacology who co-authored a recent paper on tinnitus and potassium modulators, specifically. And the response was what you got yesterday:

Dear Jakob, Thank you for your interest in the work. We do not know the mechanism of how retigabine (Trobalt) decreases induced firing of neurons, or whether this activity could suppress symptoms of tinnitus. In light of the known side effects of the drug (blue eyes, skin, tremor, etc) it is not likely to be useful for treating tinnitus, especially long term. Dr. <name withheld>'s lab is currently working on potentially more effective alternatives with fewer or no side effects. However, securing funding for this research remains an uphill battle.

And for what it is worth, there are many drugs already in circulation on the market and for which the exact mechanism-of-action is not known. Take painkillers for example: the mechanism of action in opioids is quite well defined, I believe - but not so with NSAIDs. And yet we swallow Ibuprofen, Voltaren, and Aspirin "all the time", right? [And no, I do not want a thousand examples from armchair critics proving me wrong on this - it was an example only!]

I have, and will, engage in a bit more dialogue with the "best of the best" I can find out there. But this board - or certain parts of it - also needs to come to its senses. From time-to-time.

I didn't request this workload placed upon me. I am just delivering the hard facts.

As I always do.

 

[dan]

http://onlinelibrary.wiley.com/doi/10.1111/j.1528-1167.2011.03365.x/full
http://molpharm.aspetjournals.org/content/58/2/253.short

Above are 2 studies when I do a quick Google search.

 

[Manuel Tissm]

Anyone knows if trobalt works in T in the ears (not in the head) ?
Seems bell chimes when I shake my head. - i think the sound is in the ears.

 

[rtwombly]

Anyone knows if trobalt works in T in the ears (not in the head) ?
Seems bell chimes when I shake my head. - i think the sound is in the ears.

It's a neurochemical, so works in the brain. Your problem could be in the brain, in the ears, or a combination of both. Keep looking for a good doctor, is the only advice I can give.

 

[SoulStation]

Why do you guys think this drug has been banned in numerous countries?

 

[Martin69]

Why do you guys think this drug has been banned in numerous countries?

In Germany because Trobalt was not efficient enough for epilepsy. So the health insurances did not pay for it. Therefore it was taken from the market. At least that's the information I found on the web some time ago.

I also found one forum yesterday where epilepsy patients discussed Trobalt. One guy took 1200 mg every day and had no side effects (at least he writes he tolerates it very good). Nevertheless the experiences here and the experiences of long term studies look alerting. Would be really good if Trobalt would cure or lower T after some weeks that one can taper off again.

 

[attheedgeofscience]

Why do you guys think this drug has been banned in numerous countries?

A leading question, I presume...

Well, here is a clue (it's in German, but the "red hand" at the top kind of says it all...):

http://www.akdae.de/Arzneimittelsicherheit/RHB/Archiv/2013/201306241.pdf

Although, the above is not the reason for the ban; I believe there was a pricing issue - that was the reason...

 

[jazz]

Keep looking for a good doctor, is the only advice I can give.

Agreed. But finding that good doctor. There's the rub.

 

[rtwombly]

I also found one forum yesterday where epilepsy patients discussed Trobalt. One guy took 1200 mg every day and had no side effects (at least he writes he tolerates it very good). Nevertheless the experiences here and the experiences of long term studies look alerting. Would be really good if Trobalt would cure or lower T after some weeks that one can taper off again.

Anything interesting on that forum re: long term side effects?