Levetiracetam (Keppra) — Another Possible Potassium Channel Modulator?

[hopefuldede]

This is day 3 of 250 mg of Keppra twice a day.

Right now my main and most debilitating tinnitus sound is worse.

My ultra high frequency electric sound where I had my sudden hearing loss in the right ear from ear infection that falls anywhere from 12 kHz to 15 kHz is very prominent, sensitive, and intrusive in both ears. This is my most debilitating sound especially when reactive, so I am nervous and discouraged being 3 days in on a drug that has literally done the opposite for others. I want to believe there is a chance that things could just be acclimating and get better, but I'm not aware of anyone on Tinnitus Talk who is still active and who has taken Keppra to discuss these concerns with.

So yeah, so far, increased sensitivity and intrusiveness.

Ooh @ErikaS - I am sorry. I know what you mean. You are stuck thinking is this just my body getting used to this new drug and things may get worse before it gets better and, if so, should I stay on it for a while longer, vs. is this going to worsen me - which is a risk none of us ever want to take. It's a hard one to call in the absence of anyone else that is here actively on it at present.

Xx

 

[haha ear go eeee]

This is day 3 of 250 mg of Keppra twice a day.

Right now my main and most debilitating tinnitus sound is worse.

My ultra high frequency electric sound where I had my sudden hearing loss in the right ear from ear infection that falls anywhere from 12 kHz to 15 kHz is very prominent, sensitive, and intrusive in both ears. This is my most debilitating sound especially when reactive, so I am nervous and discouraged being 3 days in on a drug that has literally done the opposite for others. I want to believe there is a chance that things could just be acclimating and get better, but I'm not aware of anyone on Tinnitus Talk who is still active and who has taken Keppra to discuss these concerns with.

So yeah, so far, increased sensitivity and intrusiveness.

It looks like @Viking's reactivity spiked the first couple of days too, but I believe theirs died down. Their loudness hyperacusis totally vanished too, oddly enough. But I get what you mean, I wish they were still on here. I'm sorry, I don't even know what to recommend. I've heard of supplementing NAC with new medications to lower the chance of spikes.

 

[ErikaS]

I am stopping the Keppra. I am honestly so let down and discouraged, but it's how life has been for me the past 4 years, so not sure why I thought it would do for me what it did for a number of people.

What is very weird is it seemed to have a very similar if not the same negative effect that Flexeril did back in April. Both made my high-pitched electric hiss tone so intrusive and reactive, and am now dealing with "ts ts ts ts" electric crap mixed in just like I did following Flexeril. So I don't know if either of these have any similar mechanisms, but they both are a no for me.

Trileptal did not make me worse, it actually gave me some of my best days in a row since my setback in April but that changed and I went back to baseline. My neurologist is out this week but hoping I hear back from him next week.

I/we need BHV-7000 or XEN1101 to trial.

 

[CaliGirl]

I saw on TV Biohaven is recruiting for OCD patients. Not sure if it is the same drug.

 

[ErikaS]

I saw on TV Biohaven is recruiting for OCD patients. Not sure if it is the same drug.

Unfortunately not the same drug

 

[ErikaS]

I am still grieving over the fact that not only did trying Keppra not do anything for my reactivity, it actually made things notably worse in a matter of 3-4 days and by day 5 I was so afraid that I stopped. I wish the Keppra at least hadn't done anything and then maybe upping the dose I could have gotten some relief or nothing, but to experience such awful reaction to it right away and feel like I couldn't give it a good effort go at it? Ugh.

What I do find interesting is both @Danny Boy and @Viking experienced this amazing reactivity "cure" with Keppra after being on Retigabine. Maybe that was an important factor in some way. Like modulating the potassium channels first, then trying Keppra? I'm not sure. I just am having a hard time accepting my experience with it I guess.

 

[Martin69]

I am stopping the Keppra. I am honestly so let down and discouraged, but it's how life has been for me the past 4 years, so not sure why I thought it would do for me what it did for a number of people.

What is very weird is it seemed to have a very similar if not the same negative effect that Flexeril did back in April. Both made my high-pitched electric hiss tone so intrusive and reactive, and am now dealing with "ts ts ts ts" electric crap mixed in just like I did following Flexeril. So I don't know if either of these have any similar mechanisms, but they both are a no for me.

Trileptal did not make me worse, it actually gave me some of my best days in a row since my setback in April but that changed and I went back to baseline. My neurologist is out this week but hoping I hear back from him next week.

I/we need BHV-7000 or XEN1101 to trial.

Your tinnitus sounds similar to mine. Very difficult to handle every day.

I took Trobalt some years ago and it helped for a few hours after each dose. I stopped because of the side effects.

I have not taken Keppra since I don't have hyperacusis.

What helped me to some extent, was Escitalopram (Lexapro), 10 mg every day. Maybe it is placebo, maybe not. But after two years of tinnitus at a non-stop level of 10/10, along with high anxiety, Lexapro brought me some relief. I now have a cycle of 4-5 days of really bad tinnitus, and then 2-3 days of lower tinnitus. It is still hell on earth, but gives me some hours to breath.

It is not always the same. I can have periods of worse tinnitus of up to two weeks and lower tinnitus of up to five days. But I know that sooner or later, a better day will come.

If things get really bad, I take a really small dosage of Mirtazapine (Remeron) to get good sleep. And my tinnitus is usually lower the next morning.

It is all about managing the tinnitus. My best friends are crickets on my mobile.

 

[ErikaS]

Your tinnitus sounds similar to mine. Very difficult to handle every day.

I took Trobalt some years ago and it helped for a few hours after each dose. I stopped because of the side effects.

I have not taken Keppra since I don't have hyperacusis.

What helped me to some extent, was Escitalopram (Lexapro), 10 mg every day. Maybe it is placebo, maybe not. But after two years of tinnitus at a non-stop level of 10/10, along with high anxiety, Lexapro brought me some relief. I now have a cycle of 4-5 days of really bad tinnitus, and then 2-3 days of lower tinnitus. It is still hell on earth, but gives me some hours to breath.

It is not always the same. I can have periods of worse tinnitus of up to two weeks and lower tinnitus of up to five days. But I know that sooner or later, a better day will come.

If things get really bad, I take a really small dosage of Mirtazapine (Remeron) to get good sleep. And my tinnitus is usually lower the next morning.

It is all about managing the tinnitus. My best friends are crickets on my mobile.

Thank you for sharing this. With XEN1101, BHV-7000, and Dr. Shore's device all in the 2-4 year ballpark, I hope for both of us managing our tinnitus becomes a lot easier, and "hell on earth" becomes more like "wow this is actually livable and no longer hell".

 

[HighleyTall]

I think I figured out the reason why Keppra works for some people with hyperacusis and reactive tinnitus. Apologies in advance if this has already been said before in this thread.

View attachment 55698

If I understood it correctly, in the synapses located at the basolateral membrane of outer hair cells (OHCs), electrical activity via the activation of voltage-gated L-type calcium channels causes releases of glutamate through vesicles into the boutons of type II afferents. We know that normally, "glutamatergic synaptic transmission from OHCs [to type II afferent boutons] is weak. Individual OHCs release single vesicles with low probability so that summed excitation from the entire pool [do not know what Fuchs means by entire pool] of presynaptic OHCs is required for action potential initiation. Maximal stimulation [?] of an OHC had a one in four chance of releasing a single vesicle during maximal stimulation. Each vesicle causes a 4-mV depolarization [of the type II afferent] on average, thus requiring 7 or more concurrent vesicles for the type II afferent to reach the 25-mV threshold for action potential initiation."

But here's the curious thing. Paul Fuchs found out that the number and size of OHC synaptic ribbons increased after mice were exposed to damaging sound. Using a statistical model Paul Fuchs estimated that a global 20 % increase in OHC ribbon count observed in the noise-exposed mice is estimated to cause a 99 % increase in action potentials [of type II afferent neurons] in response to maximal stimulation of OHCs across the entire population of 1000 (virtual) type II afferents.

In short, if I understood it correctly, acoustic stimulation --> L-type calcium channels open --> calcium ions enter the outer hair cell --> OHC depolarizes --> glutamate is sent to type II afferents --> Type II afferents depolarize.

Now, in the case of acoustic damage, because of increased ribbon number and size, the same OHC depolarization makes it more likely for a type II neuron to fire. So that is a possible reason why normally non-painful sounds become painful to people with hearing damage.

Keppra, and also Nifedipine, block the influx of calcium ions through L-type calcium channels. So theoretically it should alleviate hearing disorders where type II neurons are the culprit, as is the case with noxacusis and maybe (reactive) tinnitus as well.

This study is awesome. It is a fantastic discovery!

It really gives me hope because they are getting close to finding the cause of hyperacusis/noxacusis.

 

[AverageJoe12]

I am still grieving over the fact that not only did trying Keppra not do anything for my reactivity, it actually made things notably worse in a matter of 3-4 days and by day 5 I was so afraid that I stopped. I wish the Keppra at least hadn't done anything and then maybe upping the dose I could have gotten some relief or nothing, but to experience such awful reaction to it right away and feel like I couldn't give it a good effort go at it? Ugh.

What I do find interesting is both @Danny Boy and @Viking experienced this amazing reactivity "cure" with Keppra after being on Retigabine. Maybe that was an important factor in some way. Like modulating the potassium channels first, then trying Keppra? I'm not sure. I just am having a hard time accepting my experience with it I guess.

Hey Erika - I hope you're doing okay. Have you tried anything else to help with the reactivity/hyperacusis? I'm struggling immensely with hyperacusis (more so than tinnitus) and am just hoping to find a bit of relief.

 

[StoneInFocus]

I am still grieving over the fact that not only did trying Keppra not do anything for my reactivity, it actually made things notably worse in a matter of 3-4 days and by day 5 I was so afraid that I stopped. I wish the Keppra at least hadn't done anything and then maybe upping the dose I could have gotten some relief or nothing, but to experience such awful reaction to it right away and feel like I couldn't give it a good effort go at it? Ugh.

What I do find interesting is both @Danny Boy and @Viking experienced this amazing reactivity "cure" with Keppra after being on Retigabine. Maybe that was an important factor in some way. Like modulating the potassium channels first, then trying Keppra? I'm not sure. I just am having a hard time accepting my experience with it I guess.

@ErikaS, maybe Brivaracetam, a Keppra analog, is an option to try?

It binds to the SV2A protein with 20-fold greater affinity than Keppra and has less off-target effects. Like blockage L-type calcium channels, it should theoretically prevent OHCs from sending vesicles to type II afferents, although I'm not really sure if SV2A proteins are expressed in OHCs.

Maybe this article is of interest:

→ Brivaracetam extinguished allodynia in a murine mode of neuropathic pain

Considerable work indicates that LEV and BRV act, at least in part, via a specific mechanism involving SV2A. However, apart from SV2A, LEV has additional mechanisms of action, including inhibition of voltage-gated K+ and Ca2+ channels, inhibition of 1,4,5-trisphosphate-mediated release of intracellular Ca2+, and interactions with multiple excitatory and inhibitory ligand-gated ion channels. By contrast, BRV may be somewhat more selective. A single report suggests that BRV inhibits Na+ current in cultured rat cortical neurons, but other studies indicate that BRV does not modulate high- and low-voltage-activated Ca2+ currents, voltage-gated delayed rectifier K+ currents, and persistent voltage-gated Na+ currents, and that BRV is devoid of any direct effect on currents gated by γ-aminobutyric acidergic type A, glycine, kainate, N-methyl-d-aspartate, and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid.

Given that LEV and BRV overlap strongly in terms of SV2A binding, but not in terms of actions at ion channels or receptors, it seems plausible that the mechanism for the similar salutary effects of LEV and BRV on pain behaviors involves SV2A. The 10-fold higher potency that we observed here with respect to anti-allodynic activity, which is similar to its relative efficacy with respect to antiseizure activity, is in keeping with 20-fold greater binding affinity for SV2A by BRV28 and is in keeping with the novel hypothesis that SV2A is the relevant target of the anticonvulsant racetams in neuropathic pain.

This study is awesome. It is a fantastic discovery!

It really gives me hope because they are getting close to finding the cause of hyperacusis/noxacusis.

Would you ever give Keppra (Levetiracetam) or Briviact (Brivaracetam) a try?

I saw you did not have much success obtaining Nimodipine.

 

[HighleyTall]

Would you ever give Keppra (Levetiracetam) or Briviact (Brivaracetam) a try?

I saw you did not have much success obtaining Nimodipine.

Thanks for the suggestion. These medications seem interesting, but they seem to have some serious side effects. I'm currently fighting naked. I take some painkillers every now and then. You might have noticed I'm not that active anymore on Tinnitus Talk. I'm keeping myself as busy as possible during the day, so I'm exhausted in the evening. I don't know how long I can keep this up. I'm even doing stuff I might regret, but sitting in a room and crying in a corner doesn't help either.