Retigabine (Trobalt, Potiga) — General Discussion

[Dr. Nagler]

To be honest, I would say a typical Doctors attitude has led him to this conclusion!
(no disrespect meant)

If I had a "typical Doctors attitude," I wouldn't be here in the first place!

I was asked a question about whether or not I would prescribe a drug under certain circumstances, and I explained the thought process I was going through - for me a real struggle - in a very candid and personal way. See if that ever happens again!

Dr. Stephen Nagler

 

[Dr. Nagler]

What makes you come to the conclution that the drug is not effective?

After what just happened here, I'd have to be crazy to answer that question!

Dr. Stephen Nagler

 

[RichL]

If I had a "typical Doctors attitude," I wouldn't be here in the first place!

I give you that.

After what just happened here, I'd have to be crazy to answer that question!

I was giving an honest opinion, I did not mean any disrespect or malice in that opinion and no you would not be crazy if you answered the question, if anything you would probably earn a little more respect by some on here who are a little less trusting of the medical profession!

 

[Viking]

AICA is involved in mine. It is responsible for contact in the entrance of the acoustic pore. My 3rd tinnitus sound is like a telegrach or morse code sounds. It is more like a note that has pauses, not clicks or heart bits... I don't know if this qualifies as a "Typewriter tinnitus". And it is not the major bothering sound in my T, that is the constant steady high pitch of crt-TV like sound (15500Hz) that sometimes fluctuates.

Dearest friend;

this is about NVC, ABR confirmation,and Tegretol:

http://www.ncbi.nlm.nih.gov/pubmed/16514262

http://www.dizziness-and-balance.com/disorders/unilat/microvascular.htm

http://www.ajnr.org/content/29/9/1746.full

http://www.tinnitusjournal.com/detalhe_artigo.asp?id=371

http://www.ncbi.nlm.nih.gov/pubmed/20360168

http://www.ncbi.nlm.nih.gov/pubmed/20360161

 

[RichL]

I strongly believe that what is being experienced on this board is a combination of placebo effect, coincidence, desperation, wishful thinking and mob mentality.

I'm afraid that your strongly held belief is a little should I say...... well looking like someone who doesn't see evidence that is staring them in the face or doesn't want to see it!

Which is why I gave you my original opinion.

 

[RichL]

I would like to know the percentage of Trobolt, (Retigabine) users who have got some noticable relief from this drug.

Trials of new drugs only require a 40% success rate( just going by memory) to be seen as a beneficial drug!

 

[attheedgeofscience]

I would like to know the percentage of Trobolt, (Retigabine) users who have got some noticable relief from this drug.

Trials of new drugs only require a 40% success rate( just going by memory) to be seen as a beneficial drug!

@RichL if you take a look at the data below (from the ATA petition thread), you can see the interim and final improvements from participants of this forum who have taken Trobalt and reported their findings.

Treatment improvement is defined as "Start TI" - "End TI". Some participants had interim improvements better than the final reported score eg. "Johno" - this can be seen in the "Min" column; similarly for the worst interim scores ie. "Max" column. A final score does not mean that the treatment has finished; it is simply the last reported score at that the time the data was evaluated.

Hope this helps.

 

[amandine]

Everyone, for what it is worth, I can tell you that @Danny Boy is finding great relief with Trobalt.So far it has literally saved his life and sanity. What happens as time progresses no one knows but so far it has been quite successful. He had a blip when he went from 100 x 3 to 200 x 3 per day but now he is on 500 x 2 per day = 1000mg per day, he is doing well. Yes he gets a little high shortly after taking the dosage but this wears off and he is back to his normal self but with very low T sound in his head.
His headache I think is the cost of the drug as he cant get it prescribed for him although he is still trying that route.
Personally I would like to join him on this trial and am looking into it for myself as there is nothing else we can do.
Slightly off topic but to explain the choices that are left:
Alternatively there is autifony or Jacqui Sheldrake re @Dr. Nagler for TRT.
I know no other routes unless @Viking can tell us in a month that keppla has helped. I sure hope so cos this means that we dont have to worry about all those possible nasty side effects with Trobalt which frighten the life out of me and many others here.
So far Trobalt has shown to be the most effective treatment on this forum, whether it is permanent or not.

 

[inadmin]

After what just happened here, I'd have to be crazy to answer that question!

Dr. Stephen Nagler

So try ignoring that maybe putting emotions aside, because i am interested in hearing your opinion.

 

[Dr. Nagler]

OK, @inadmin ...

Retigabine has been used in the treatment of seizure disorders since 2011 and has been under clinical study in that regard for years prior to its release. Given that 20% of the population has tinnitus, it is reasonable to assume that 20% of the individuals on Retigabine for seizure disorder have tinnitus. Being very conservative and looking only at the 4% of the population suffering from severe intrusive tinnitus, if a substantial percentage of those individuals experienced diminution of their tinnitus on Retigabine, big pharma (which is all about money and profit) would by now already be on it like white on rice.

The above was my thinking at the time of the Campral debacle, when so many were convinced that it provided relief ... until properly controlled studies showed that it didn't. And it is my thinking today regarding Retigabine.

Is it possible that the fine folks on this board have discovered the holy grail of tinnitus that has been right under big pharma's noses all the time? Sure it is. But in my opinion it's not likely, not considering the gazillions of dollars that big pharma tends to make if there is really anything to it.

Dr. Stephen Nagler
(who would really love to be wrong about this!)

 

[xanaxvictim]

So try ignoring that maybe putting emotions aside, because i am interested in hearing your opinion.

He had made it very clear, there is NO double blind placebo controlled study that confirm RTG is effective. and he believed that RTG does not work because in the past all candidate drugs failed double blind placebo controlled trials so he does not believe there exists a pharmacological approach can cure/suppress T.
Until we have double blind placebo controlled data on RTG effectiveness nothing can be said about its effectiveness in this respect.

 

[Rube]

OK, @inadmin ...

Retigabine has been used in the treatment of seizure disorders since 2011 and has been under clinical study in that regard for years prior to its release. Given that 20% of the population has tinnitus, it is reasonable to assume that 20% of the individuals on Retigabine for seizure disorder have tinnitus. Being very conservative and looking only at the 4% of the population suffering from severe intrusive tinnitus, if a substantial percentage of those individuals experienced diminution of their tinnitus on Retigabine, big pharma (which is all about money and profit) would by now already be on it like white on rice.

Is it possible that the fine folks on this board have discovered the holy grail of tinnitus that has been right under big pharma's noses all the time? Sure it is. But in my opinion it's not likely, not considering the gazillions of dollars that big pharma tends to make if there is really anything to it.

Dr. Stephen Nagler
(who would really love to be wrong about this!)

Big pharma must have some idea which is why Autifony is moving ahead with the potassium channel theory. I also can't recall who it was but there is more experimentation being performed to make trobalt more specific and create less side effects.

 

[amandine]

@Dr. Nagler

Going on from what you have said earlier in this thread re trobalt and placebo effect including your above post and following the logic of it, it would seem that (in your opinion) for most of us including yourself this T is due to psychological reasons -- if the Trobalt is acting as a placebo.

I ask this cos I am personally aware of the difference it Trobalt has made to Danny Boy who is now immensely better taking this drug.

It has to be said to be absolutely fair that he did find slight and temporary relief from other things he tried (listening to Mozart for example or neuromodulation sounds) but on the Trobalt he is finding much more enduring relief day after night after day.

In other words our minds are the cause of the perception of this noise and our minds can be the effective control or elimination of it. That is the placebo effect is it not?

(Dont understand why then it is louder after a good long sleep when it is supposed to go down after a long med free sleep. How can the mind ramp it up after a long sleep?)

So any treatment which deals with the mental issues behind it in whatever way, be it placebo, prayer, CBT, EFT, ART, TRT or any treatment that is believed in can result in a reduction or near elimination from our consciousness?
Would that be the logical conclusion Dr. Nagler?
Really appreciate your opinion.

Retigabine has been used in the treatment of seizure disorders since 2011 and has been under clinical study in that regard for years prior to its release. Given that 20% of the population has tinnitus, it is reasonable to assume that 20% of the individuals on Retigabine for seizure disorder have tinnitus. Being very conservative and looking only at the 4% of the population suffering from severe intrusive tinnitus, if a substantial percentage of those individuals experienced diminution of their tinnitus on Retigabine, big pharma (which is all about money and profit) would by now already be on it like white on rice.

Is it possible that the fine folks on this board have discovered the holy grail of tinnitus that has been right under big pharma's noses all the time? Sure it is. But in my opinion it's not likely, not considering the gazillions of dollars that big pharma tends to make if there is really anything to it.

Dr. Stephen Nagler
(who would really love to be wrong about this!)

 

[xanaxvictim]

@amandine
I think the only way we can know the objective loudness of a subjective T is by minimum dB of masking white noise not the TQ stuff which is subjected to psychological effects. By using masking sound you either hear T or not. This is potentially valuable in validating whether the improvement reported here is psychological effect or not. I don't believe the effects of RTG are all placebo though, the question is whether it affects T perception like benzos do or it really has an influence on the T signal itself (if the latter is true it will be a huge discovery).

We do have evidence that objective T loudness has a neurological component independent of psychological issue (Depression/Anxiety)
that tinnitus loudness ratings were negatively correlated with MD in the anterior thalamic radiation and anterior and superior corona radiata (although significantly so only in the left hemisphere); (4) that compared to age-matched controls, tinnitus patients had higher FA and lower MD in anatomically defined regions of interest in the white matter tracts underneath both auditory cortices (ACx) and inferior colliculi (IC); and (5) that in anatomically defined ROIs in ventromedial prefrontal cortex (vmPFC), FA correlated positively and MD correlated negatively with tinnitus loudness ratings. Depression and anxiety, while tending to be higher in tinnitus patients than in controls, could be ruled out as alternative explanations for these findings.
http://www.hindawi.com/journals/np/2014/145943/

In the future functional neuroimaging may help but at the moment we don't have an established connection of a particular BOLD signal to T loudness. Things may change in the future though, researchers are trying to use machine learning algorithm to try to find out the BOLD signals which correspond to T.

 

[skoupidis]

People, this is all theoretical, the dear doc said his opinion, it is up to the brave testers to prove him wrong. I myself am confident that if I try Retigabine I will immediately tell, after a fair amount of time, if it works or not for me. Since whatever I did try until now did absolutely nothing... Permanent or temporary that is.

You see I can hear mine quite clearly, even in a noisy room (every sound aggravates it). Mine is a wild animal, cannot be tamed but for little unexplained moments of the day, I wish I could put it to death more than anything!

Having said all that, I too am so damn skeptical about this drug and if it really helps with this terrible and uncontrolled condition of ours. Mtp (the author of this long post) was the first to do so, and was cured. But he is the only one who was really (?) cured so far. It is possible something else happened for his condition. He did get T quite oddly I might add... not from acoustic trauma, or drugs or something. If I remember correctly he did get it from cleaning his ear or something? Perhaps he can confirm, if he is still with us, and tell us if he is till on Regitabine.

 

[OddV]

I would like to know the percentage of Trobolt, (Retigabine) users who have got some noticable relief from this drug.

Trials of new drugs only require a 40% success rate( just going by memory) to be seen as a beneficial drug!

If I did my math right, it's a 40% improvement on the nose.

 

[attheedgeofscience]

If I did my math right, it's a 40% improvement on the nose.

Agreed.

And/but, there is a difference in obtaining an average improvement in tinnitus intensity and obtaining meaningful relief amongst participants.

For instance, in the above post...

https://www.tinnitustalk.com/threads/retigabine-trobalt-potiga-—-general-discussion.5074/page-117#post-84239

...4 out of 17 participants experienced an improvement of 4 intensity points (or more) between their start and end result. By that definition, you could argue that the drug was only effective in 24% of the cases. Of course the above informal trial summary does not consider factors such as etiology, treatment duration, dosage level, chronicity, and age - and so it could well be that the drug under specific circumstances has a much better performance than 24%.

The informal trial data is just for indicative purposes. Please do not start to draw conclusions on this data; that is what a proper trial would be for.

Thanks.

 

[xanaxvictim]

muscarinic receptor signaling
reduction of PIP2
I have a gut feeling that this may have something to do with the loss of effectiveness of RTG after long term use, anyone interested in researching into this issue?

http://www.ncbi.nlm.nih.gov/pubmed/23650395

Pharmacological augmentation of neuronal KCNQ muscarinic (M) currents by drugs such as retigabine (RTG) represents a first-in-class therapeutic to treat certain hyperexcitatory diseases by dampening neuronal firing. Whereas all five potassium channel subtypes (KCNQ1-KCNQ5) are found in the nervous system, KCNQ2 and KCNQ3 are the primary players that mediate M currents. We investigated the plasticity of subtype selectivity by two M current effective drugs, retigabine and zinc pyrithione (ZnPy). Retigabine is more effective on KCNQ3 than KCNQ2, whereas ZnPy is more effective on KCNQ2 with no detectable effect on KCNQ3. In neurons, activation of muscarinic receptor signaling desensitizes effects by retigabine but not ZnPy. Importantly, reduction of phosphatidylinositol 4,5-bisphosphate (PIP2) causes KCNQ3 to become sensitive to ZnPy but lose sensitivity to retigabine. The dynamic shift of pharmacological selectivity caused by PIP2 may be induced orthogonally by voltage-sensitive phosphatase, or conversely, abolished by mutating a PIP2 site within the S4-S5 linker of KCNQ3. Therefore, whereas drug-channel binding is a prerequisite, the drug selectivity on M current is dynamic and may be regulated by receptor signaling pathways via PIP2.

 

[Christian78]

Come on my friend, hang in there. This community shows GREAT potential, and it is a light of hope for all of us. It is understandable how you feel though, believe me, it is sad but true. But we must not give up. This terrible condition makes doctors obsolete and on the other hand this forum MUCH more helpful than them. Even if you feel hopeless, we all have a purpose here. Plus reading and writing is something we can manage despite our monster that ripped us of other pleasures!
Hope that something is happening, especially with this drug sooner than the companies can provide for us is something really exciting. Personally, I do dream of a new scientific discovery that is (finally) put to test and apply succesfully in human beings. Let's hope this day comes closer and closer. A human being has already tried something really promising if succeed, the virus thing. Could turn everything around that one...

there is no comunity like silence, you wont believe it i was on trobalt 200-250 and i amo9st lost t, now when it came back it is terrible, death is my only solution, they just lie they develop only for 6-12 month, for us old nothing we are left to die. And it is truth. I use 300x3 and I am on really dark place my t varies but my blood pressure went down, my hands are shaking now i cant understand words, cant sign my name, i could that but after 3 months on trobalt my brain started to go down really down, more deep in side effects, less effect from trobalt on tinnitus.

Can you imagine how it is to lose t on 2,5 months and then get it back, and then be aware you will get it but you must stop medicine to retry and you know what will you be surviving, you dishabituated and is seem trobalt raised a bit t, but H definitely.

one bad side of trobalt is that you stop protecting your ears becouse you are drugged so you can worsen yout t intensivly

 

[Christian78]

@RichL if you take a look at the data below (from the ATA petition thread), you can see the interim and final improvements from participants of this forum who have taken Trobalt and reported their findings.

Treatment improvement is defined as "Start TI" - "End TI". Some participants had interim improvements better than the final reported score eg. "Johno" - this can be seen in the "Min" column; similarly for the worst interim scores ie. "Max" column. A final score does not mean that the treatment has finished; it is simply the last reported score at that the time the data was evaluated.

Hope this helps.

View attachment 4120

Because i have problems with trobalt i have been excluded? We are doing make up of results...

 

[skoupidis]

@Christian78 my friend I will try to understand what you are saying although I find it extremely difficult...
You say you had a temporary relief from T for two and a half months, but it then came back although you where still on Trobalt? And now it doesn't help you even if you increased the dosage?

Are you also saying your Hyperacusis didn't get any help from Retigabine?

 

[Christian78]

@RichL if you take a look at the data below (from the ATA petition thread), you can see the interim and final improvements from participants of this forum who have taken Trobalt and reported their findings.

Treatment improvement is defined as "Start TI" - "End TI". Some participants had interim improvements better than the final reported score eg. "Johno" - this can be seen in the "Min" column; similarly for the worst interim scores ie. "Max" column. A final score does not mean that the treatment has finished; it is simply the last reported score at that the time the data was evaluated.

Hope this helps.

View attachment 4120

And you need how many moths have they used it, what is that about 1 months on a drug! , 6 months is minimum, or?

 

[Christian78]

@Christian78 my friend I will try to understand what you are saying although I find it extremely difficult...
You say you had a temporary relief from T for two and a half months, but it then came back although you where still on Trobalt? And now it doesn't help you even if you increased the dosage?

Are you also saying your Hyperacusis didn't get any help from Retigabine?

I believe Trobalt increased H.

I have t now 4 maybe 3, i had spike of 9 and clonazepam helped only. I used before 900mg per day and i did not had such side effects as now, and Tinnitus dont react any more on trobalt.

I have been using trobalt and on 600mg/d i was ok, 2-3/10 tinnitus, then he started going up so i rased dosage, anyway i had to say 2-3 months of low level t on ca 2-3(max 4,5)/10 , but then steady it ven up every day up up up up up until it reached lvl 10. i combine now acrn and praying that i dont get spike.

UNDER TROBALT I WAS FREE FROM TINNITUS FOR CA 3 MONTHS. do you understand now?

 

[1MW]

@Christian78 have you tried corticosteroids ?
trobalt is not a cure lowers the T but T is only the symptom of a disease or dysfunction.
So you must check what else happen and you get T you must find the cause and treat the cause.

 

[tomm]

@amandine
I think the only way we can know the objective loudness of a subjective T is by minimum dB of masking white noise not the TQ stuff which is subjected to psychological effects. By using masking sound you either hear T or not. This is potentially valuable in validating whether the improvement reported here is psychological effect or not. I don't believe the effects of RTG are all placebo though, the question is whether it affects T perception like benzos do or it really has an influence on the T signal itself (if the latter is true it will be a huge discovery).

We do have evidence that objective T loudness has a neurological component independent of psychological issue (Depression/Anxiety)
that tinnitus loudness ratings were negatively correlated with MD in the anterior thalamic radiation and anterior and superior corona radiata (although significantly so only in the left hemisphere); (4) that compared to age-matched controls, tinnitus patients had higher FA and lower MD in anatomically defined regions of interest in the white matter tracts underneath both auditory cortices (ACx) and inferior colliculi (IC); and (5) that in anatomically defined ROIs in ventromedial prefrontal cortex (vmPFC), FA correlated positively and MD correlated negatively with tinnitus loudness ratings. Depression and anxiety, while tending to be higher in tinnitus patients than in controls, could be ruled out as alternative explanations for these findings.
http://www.hindawi.com/journals/np/2014/145943/

In the future functional neuroimaging may help but at the moment we don't have an established connection of a particular BOLD signal to T loudness. Things may change in the future though, researchers are trying to use machine learning algorithm to try to find out the BOLD signals which correspond to T.

This is a very good point. As mentioned in one of these trobalt threads I had masking tested before and after trobalt. Masking level had not changed - much to my surprise. It was identical. It's a study of one, but only my perception of the loudness has changed on ret.

 

[attheedgeofscience]

Because i have problems with trobalt i have been excluded? We are doing make up of results...

@Christian78 this was the issue that I highlighted a little while back in the following post:

One point to take note of is: for a participant to be included in the summary, it is necessary to have reported both a start user form AND at least one progress user form (otherwise basic calculations cannot be computed). There were also other assumptions, but the one just mentioned is the main one.

I realize that you have since taken action to rectify the issue by posting a NEW USER FORM (thanks!), but a new extract of data from the database has not been done since the above summary was made. At some point there probably will be a new extract done from the database and you will be included (almost certainly).

The data being provided by everyone in relation to their experience with Trobalt is potentially quite important for our Team Trobalt project. So thanks to all.

attheedgeofscience
20/DEC/2014.

 

[skoupidis]

Dearest friend;

this is about NVC, ABR confirmation,and Tegretol:

http://www.ncbi.nlm.nih.gov/pubmed/16514262

http://www.dizziness-and-balance.com/disorders/unilat/microvascular.htm

http://www.ajnr.org/content/29/9/1746.full

http://www.tinnitusjournal.com/detalhe_artigo.asp?id=371

http://www.ncbi.nlm.nih.gov/pubmed/20360168

http://www.ncbi.nlm.nih.gov/pubmed/20360161

Trying to sum up all the precious info gathered above:
Very informative, although ambiguous in their conclusions... many of them can't be certain of Tinnitus being caused by VC. Not to mention a steady high pitched tone like mine, which is nonpulsatile T. And this is the most troublesome... Quite a few papers I've read though do point out relief in such nonpulsitile tupes of T after mvd surgery. I think more extensive studies had been done by Nowé et al who stated that "nonpulsatile tinnitus may result from a microvascular compression at the cisternal segment of the eighth CN" and showed a "correlation between the clinical presentation of nonpulsatile tinnitus (high and low pitch) and perceptive hearing loss".

These are important findings indeed, backed up by surgical evidence of relief in such patients. If these findings are true and accurate, they may lead to a more specific study for Tinnitus causes even if acoustic trauma is involved. That is why there are those who even having hearing damage from loud noise, they may not experience Tinnitus. And those that have T even if there is no history of acoustic trauma. Perhaps this approach is a more current and a more correct one too. A correlation between acoustic trauma when vascular compression is present should also be attended.

Just out of curiosity: Are there people out there with T and not having some kind of vascular compression of the 8th nerve? Have they checked it? With proper exams (ear MRI)? Looked into by proper doctors who can read such abnormalities?

 

[skoupidis]

@Viking
You say you have not have your T due to acoustic trauma. Also that vascular compression (of what type exactly) was taken care by surgery, though your T didn't completely disappear. You also say that Trobalt helped you A LOT and unfortunately couldn't continue. Since your T is of vascular confict, is it safe to conclude that Retgabine also helps in such cases? How long have you been on Trobalt? Did you experience immediate relief? Also, is your T high-low pitch continued noise, or typewriter like?

And now a couple of questions for everybody:
I experience variations in my T while walking, like every time I press one foot to the ground there is a zip like sound, a sudden spike in my T. I goes like that with every step I take. Like my shoes are wet or something... Do you people hear something like that?
My T also reaches its TOP when I open my mouth to full extend. I reaches top levels of volume, coming from my right ear alone. Like while the mouth opening enhances gradually the already steady tone I have to full extend!

 

[1MW]

@skoupidis i have similar symptoms and my symptoms resolve with corticosteroids.
I have not tried trobalt yet.
For example yesterday i had T 5 / H /ear pressure-blockage and after getting 24mg methyprednisolone before bedtime today T is 0.1-0.5 and H reduced dramatically .
If i have not taken corticosteroids and i smoke 2 cigarettes T from 5 goes to 9 but when iam
on corticosteroids smoking does not effect T.
For T i have tried almost all benzos by far the better result is from lorazepam
is the more strong and potent if i have low T my T stops with 2.5mg (not changing emotional response like clonazepam/alprazolam it lowers/stops T)
but lorazepam causes strong addiction and dependence stay away from this.

 

[skoupidis]

Corticosteroids after almost 5 years of T onset??
I tried my corticosteroids 5 days after my onset, and intravenously in my 9-13 days (hospitalized) period after the onset. They did NOTHING.
Anyway, corticosteroids are meant for treatment, not chronic use. They help inflamed cells get back their good state. They cannot bring back dead cells. How long ear cells remain inflamed before they die? I don't know, perhaps a doctor could help us here.
I myself try for a second time (after the first month of my onset) corticosteroids (celestone chronodose), 3 injections in 3 weeks. Yesterday I did my second, no change yet. The therapy is combined with neurobion injections (3 a week) and 3x300mb Neurontin (Gabapentin).

I will keep you informed but I do not believe anything happens...