Zonisamide for epilepsy in squirrel = no dice

[LeilaNami]

Hello everyone,

I wasn't sure where to put this, so I placed it in this forum. Feel free to move it.

I posted asking about zonisamide for a seizure squirrel in the past. Originally she was placed on phenobarbital to control her seizures, which it did so pretty well. However there are concerns with side effects so the veterinarian wanted to see if zonisamide could be used effectively. There is no published dose for epileptic rodents and is relatively new but has been used as an alternative for epilepsy in dogs and cats. We started to wean her off pheno four days ago. She was receiving pheno in the AM and zonisamide (at 7.5 mg/kg) at night. Today she had multiple seizures so we've placed her back on a pheno-only treatment plan.

I just wanted to give an update on zonisamide though we didn't have any luck with it. It may still be an effective alternative if the dosage is played around with but because this squirrel tends to have multiple seizures in a row, the vet opted to go back to what works for now.

[island rehabber]

Thanks for posting this, LeilaNami -- good info.
As the mamma of a seizure squirrel, I am forever on the lookout for info on whether something works. Or doesn't.

[pixiepoo]

Have you tried potassium bromide along with the pheno? That was the only thing that really helped my little Pixie's primary seizure disorder. If you haven't tried it you may want go look into it :)

[LeilaNami]

No prob, IR!


Have you tried potassium bromide along with the pheno? That was the only thing that really helped my little Pixie's primary seizure disorder. If you haven't tried it you may want go look into it :)

We have not actually. Zonisamide was the first alternative we tried. Pheno by itself works well to control them, but we are concerned with the potential for liver damage with long-term use. I don't think I'm going to try to change her treatment plan again, at least for right now. She had some very bad seizures this last time and now has developed a tic on the right side of her body. It's not a bad one but I'd at least like to see if it's going to be permanent first (not to mention, I'm apprehensive about doing anything for risk of further brain damage).

[pixiepoo]

I didn't realize that the pheno alone was helping the. :) I don't blame you about not wanting to switch. We only used the PB because the phenobarb didn't work. I hopr your little sweetie makes a full recovery and gets back to normal. Fortunately pixie never has any lasting complications from her seizure.

[LeilaNami]

I think other than worrying about her health, one of the most frustrating things is that her personality has flip-flopped. I can't tell if this is a normal aggression cycle or she's just going to be a permanent butthead now. It seems to have started a downward spiral ever since her seizures started in March though it seems she only hates me (not my husband) and only in her room and only during the day. :tap My feelings are getting hurt lol.

[LeilaNami]

Well a quick update: She still has the tic. We got a new bottle 2-3 days ago of pheno and the pills cut were larger than usual. I mentioned it but the tech seemed to think it was fine. Today she's walking around like she's drunk after taking the new pills for 2 days or so. She's very alert, eating, and playful but she's sleeping a lot and wobbly. I think my gut was right and that the pills were cut too big so she's getting a larger dose than normal. I talked to the vet and was told that this was one possibility and to monitor her for right now (and bring her in if she gets worse).

[squirrelsrule&bunniestoo]

How did you go about reducing the phenobarbital dose and introducing zonisamide? I have no idea if zonisamide is effective in squirrels, but I feel like your transition might have been too quick.

The issue with seizure medications is that they take a while to reach steady state blood levels that are protective against seizures. For example, phenobarbital takes 2-3 weeks. That means that if you just start a squirrel on phenobarbital, it'll take a couple weeks before they are at the therapeutic level. It's still better than nothing before steady state, but it's not gonna be fully protective. Zonisamide time to steady state is a little less than a week in a dog. It may be different in a squirrel, but it's probably longer than a few days.

So, when you started her on the zonisamide, the best way would have been to keep the phenobarbital dose the same for about a week while adding in the zonisamide. Then reduce the dose by a small amount (I believe 1/4 reduction in dose to start with and then another quarter reduction in one month, but I can verify that tomorrow). I would probably stop at 1/2 the original phenobarbital dose with the full dose of zonisamide added onto it (10 mg/kg BID is what I see for dogs and cats that are also on phenobarbital, may be different in squirrels). If you see increased seizure level after reducing, then you go back up in dose.

[LeilaNami]

How did you go about reducing the phenobarbital dose and introducing zonisamide? I have no idea if zonisamide is effective in squirrels, but I feel like your transition might have been too quick.

The issue with seizure medications is that they take a while to reach steady state blood levels that are protective against seizures. For example, phenobarbital takes 2-3 weeks. That means that if you just start a squirrel on phenobarbital, it'll take a couple weeks before they are at the therapeutic level. It's still better than nothing before steady state, but it's not gonna be fully protective. Zonisamide time to steady state is a little less than a week in a dog. It may be different in a squirrel, but it's probably longer than a few days.

So, when you started her on the zonisamide, the best way would have been to keep the phenobarbital dose the same for about a week while adding in the zonisamide. Then reduce the dose by a small amount (I believe 1/4 reduction in dose to start with and then another quarter reduction in one month, but I can verify that tomorrow). I would probably stop at 1/2 the original phenobarbital dose with the full dose of zonisamide added onto it (10 mg/kg BID is what I see for dogs and cats that are also on phenobarbital, may be different in squirrels). If you see increased seizure level after reducing, then you go back up in dose.

She wanted me to just give her morning dose of pheno and replace the PM dose with zonisamide. She was effectively getting half her daily dose of pheno with half her daily dose of zonisamide. There is no literature on zonisamide in rodents for treating epilepsy though I do know it helps your rat not be an alcoholic (reduces ethanol consumption). I was thinking the same. Also the pheno pills were cut in smaller chunks than usual so that might have also compromised her.

On another note, she sometimes has a little bit of a lean today and just now woke up irritated and rubbing the ear on the side she occasionally leans to. This is the first time I've witnessed her rubbing her ear. I'm wondering now if she has an ear infection.

[squirrelsrule&bunniestoo]

Not too sure about the ear, but if you're interested in trying the zonisamide (which does have fewer side effects) I'd talk to your vet again about a slower transition. I'm not surprised at all that she had seizures if her phenobarbital dose was suddenly cut in half. Biggest rule of thumb on seizure patients is no drastic changes in their meds. You wanna make this transition slowly, over a couple of months. So, I'd talk to them about starting her on her normal phenobarbital dose PLUS zonisamide at whatever dose you ultimately want her on of zonisamide. Do that for 1 week, then decrease the phenobarbital dose by a little bit (I think 1/4 the dose, but I'm gonna check today) and keep at that dose for 1 month, then reduce down by another 1/4 if she has no issues on the reduced dose and stay there if that's where you want her to be med wise.

I agree that phenobarbital can be scary, but we had a lot of patients on neuro that were on it lifelong and were doing OK. We monitored their blood levels of phenobarbital and liver values often, though.

[TubeDriver]

I think SRBT has a really good point about the cross taper. I work in child clinical research including DB med trials and we have been successful using a much slower cross taper than is generally recognized to introduce new treatments in children. I can understand your hesitation to try this again but if liver results force you to consider options in the future, insist on an extra long cross taper both to reduce any withdrawal effects and to allow a slow introduction to the new agent.

[LeilaNami]

Thank you for the advice SRBT and TubeDriver! I will consider whether I want to try again or keep her on pheno. One of the things I worry about with pheno is that this vet doesn't think it's necessary to check her blood and liver values though I don't know if that will change long term (she's been on it since March). If I can't get anyone to check her values, I'm concerned about keeping her on a med with that potential side effect.

And I'm pretty sure now it's an ear infection and not a side effect of the pheno. The ear is sensitive to the touch and she woke up several times irritated and trying to rub it. She has a vet appointment scheduled.