Mirtazapine and Serotonin Syndrome issue

Ok, so my cat does not have diabetes however this is one of the only sites where i have been able to find any information about mirtazapine.
My Nova is 14 and recently had an instance of throwing up after receiving aspirin, up until that point she was eating even after the vomiting. Well, I took her to the vet and he gave her an anti nausea med and prescribed an anti biotic as a precaution. Well, after the antibiotic she stopped eating and drinking. She went back to the vet on the 1st and she gave her subcutaneous fluids, an injection of buprenophine Hcl SR 3 mg/ml at .36 of a dose and .50 of 7.5 mg of mirtazapine. Today she has finally begun eating her regular food and drinking on her own, but I have noticed symptoms of serotonin syndrome in her - I think. She seems to be having mild tremors in her face/head. I called the vet back and told her my suspicions which she had never heard of happening before, so she looked up an antidote cyproheptadine, however, I do not want to give her any more medication if I can help it.

Does anyone know how long the mirtazapine will take to totally leave her system and if the serotonin syndrome will also disappear once the drug leaves her body. I should mention that the injection was at 11 am yesterday, I noticed these symptoms at about 8pm last night and at the time I thought they were related to the amount of stress and medication the cat had received in just a couple of days. Also it is difficult for her to sleep I think because of the tremor. Her eyes are still very dilated which I am not sure is because of the mirta or the buprenorphine, or both.

I just want her to get better and not worse, does anyone have any insight ? I am desperate

 

Hi Kristin,

Your vet is right. Your kitty should get cyproheptadine ASAP if she's showing signs of serotonin syndrome: it's potentially life-threatening. If she were mine, I'd be looking to get her some cyproheptadine as soon as I possibly could. One eighth of a low-dose mirtazapine tablet is potent in a 10lb cat for about three days.

My cat, Saoirse, only ever received one dose of mirtazapine and her pupils were like dinner plates plus she had other quite alarming side effects. I didn't know about its potential to induce serotonin syndrome so I was quite shocked when I checked her symptoms against mirtazapine side effects online. Thankfully I had given her even less than an eighth of a tablet but I still had a very worried 72 hours before I was sure most of it was out of her system.

Your situation is further complicated by the presence of buprenorphine in the mix. It will likely increase the risk of serotonin syndrome in your cat (it can do so in humans - see this PubMed article). I would contact the vet immediately about this as well and if it were my cat I would not give any more buprenorphine until cyproheptadine has been administered and risk of serotonin syndrome has been removed. (You should also be cautious if your cat is receiving any supplements containing SAMe when buprenorphine has been prescribed because, based on my experience with Saoirse, SAMe can potentiate the effect of buprenorphine.)

Cyproheptadine is also an appetite stimulant but it is an antihistamine, not an antidepressant. It is much gentler in action than mirtazapine and is effective at small doses (e.g. 1/8 of a 4mg tablet every 12 hours for a 10lb cat). When I gave cyproheptadine to Saoirse alongside a very moderate dose of buprenorphine (o.1ml, max q.12) the bupe/cypro combination made her a bit drowsy for a while but aside from that she was grand. It's a much less risky combination than mirt/bupe. Your vet should be able to confirm this to you.

(I was once prescribed mirtazapine for PTSD; I nearly went insane on it after only a few doses. No hyperbole.)

Please can you come back and let us know what's happening. I remember how frightened I was about Saoirse's reaction to mirtazapine.


Mogs

EDITED TO ADD:

Just to confirm, I have no veterinary training or qualifications. You will need to validate the information I have provided above with a qualified veterinary professional.
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PS - some vets choose mirtazapine as an appetite stimulant for ease of administration (one dose every 3 days) and for its alleged anti-nausea properties.

Cyproheptadine also has anti-emetic properties but has a much less risky side effect profile. Importantly, sometimes too high a dose of cyproheptadine is prescribed for cats and this can be both too sedating and it can cause depressed mood. Starting with a tiny dose is the best way to gauge how a cat tolerates it. Because it wears off quicker it is much easier to control the level of appetite stimulation to match the needs of the cat.

Saoirse had a very bad pancreatitis flare last year. I couldn't get her to eat. Cyproheptadine helped to save her life. If Nova is nauseated, generic ondansetron is a very effective anti-nausea medication. (NB - Zofran, the branded version of ondansetron, is hideously expensive in the UK and I would assume elsewhere in the world. Also, be wary of Zofran Melts as they contain an artificial sweetener so one to be avoided.)


Mogs
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the buprenorphine was a one time thing, thankfully. i have noticed that her symptoms have decreased significantly since yesterday. That is why I wondered if I should wait it out one more day, or until the morning. I am so afraid of one more thing going wrong right now, especially since the vet isn't open on the weekends. They have been calling every day to check on her, but its unfortunate when I know better what is happening with her than they do

 

She is finally eating and drinking on her own and frequently thank god! I am just wondering how much I should give to her because the vet said 1 pill (which I think was 2 mg) every 4-6 hours till symptoms dissipate but I am afraid to give her too much of anything at this point. I feel like i have done nothing right since she got sick

 

Was that the dose for mirtazapine?????? What strength of tablet?

 

it was .50 of a 7.5 mg tablet she received so 3.25 mg ? Math is not my strong suit

 

There are many of us here who have felt the same way. It's so hard that our little ones can't speak to us. Try to focus on the positives. (Not easy, I know ...)

 

I'm just going to see if I can find the tablets Saoirse was prescribed. Back shortly ...

 

sorry, i am so tired it has been a very long weekend in this household. If Im not mistaken the antidote was a 2mg tablet to be used every 4-6 hours as needed

 

thank you so much
i am so blown away that my vet didn't even know what to do

 

thank you. its so hard.

 

I was incorrect it is 4mg
for the antidote

 

I just gave her half a tablet for now I figure its better to start with a lower dose and increase if necessary

 

Drat! Can't find the pill bottle for the mirtazapine.

You have the cyproheptadine? That's good. I can understand your worry over giving cats pills. I'm very conservative about it as well - quadruply so after Saoirse's experience with the mirtazapine. (The effect it had on her was not pretty.)

Thanks for coming back with the additional information. I've not had to give cyproheptadine as an antidote for serotonin syndrome so I don't know anything about dosing in that situation or what clinical signs to watch for. Are you able to stay in continuous contact with your vet as you monitor Nova?
,

 

Yes, there is an emergency line I can call if need be, but right now we both need sleep so badly

 

Boy, do I know how that feels. I'm very glad to hear that you've got good out of hours cover from your vet.

That's a fairly high dose, and with bupe in the mix it doesn't help. Bupe has a relatively long half-life and so does mirtazapine in a cat.

From petplace.com:

As best I can recall, the 1/8 of smallest tablet dose is what Saoirse received and she was not on bupe. Our vet nurse split the tablets into the tiny doses for me. The vet who prescribed it for Saoirse said that mirtazapine used to be prescribed at 1/8 tablet every 24 hours but they found that the effects lasted a long time - about 3 days - so they now leave a much longer interval between doses when prescribing it.

Is Nova drinking plenty? How is her temperature? How are her pupils now?
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I ended up giving her the whole 4mg. She's drinking a lot of water right now. I don't know how long it should take to see an effect I think I read about 2 hrs

 

I'm so afraid I'm going to hurt this cat with all this chemistry. But serotonin syndrome can be fatal too. It's like a catch 22

 

I'm glad to hear that she's drinking. Keep an eye on her temperature.

I'm not clear whether your vet gave you buprenorphine for home administration. If yes, then I'd suggest checking with the vet before giving it again. As I mentioned earlier, I found that treating my cat with buprenorphine at the same time as giving her cyproheptadine did have a marked sedating effect - and those were at small doses (0.1ml bupe, 0.5mg cyproheptadine).

I just had a quick look online and I can't find much about cyproheptadine as an antidote for serotonin syndrome. Here's a PDF with a little information but I have no idea of its accuracy or reliability.

(For future reference, if ever you need to treat Nova for nausea again while at the same time needing to give her something for pain, the drug ondansetron that I mentioned earlier has a major drug interaction with a painkiller called Tramadol. Joint administration of ondansetron and Tramadol may also trigger serotonin syndrome. I always worry about giving meds to my Saoirse, so nowadays I always check drug side effects and interactions myself; I don't assume our vets will know all of them and I'd rather know the risk profile of a medication before giving it to Saoirse. That said, she has chronic pancreatitis as well as diabetes and the insulin and medications she received saved her life and I'm beyond grateful.)

I need to sign off now. I have PTSD so have little or no control over my sleeping and I'm about to pass out. I'd suggest frequent monitoring of Nova's clinical signs (breathing, temperature, hydration) just to make sure she's OK. Needless to say, don't be shy about ringing your vet if you're worried about anything.

Fingers and paws are being crossed in the Shire for the cypro to help Nova feel better very quickly. I hope you both have a safe and uneventful night and that you both feel better in the morning. Needless to say, if you still need help - or even a bit of moral support - do post again. Other members here may be able to help. Please keep us updated with how you both get on. We'll be worrying about you both.


Mogs
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I understand completely. I also havenjoy ptsd and I get almost hallucinations when I'm tired. The bupe was an in office shot , one time and done.

 

Should read have* have I mentioned I shouldn't type whUlead this exhausted. Lmao

 

There has been a lot of backspacing and deleting at this end tonight.

I'm very sorry to hear you have PTSD. That'll make your worry over Nova several orders of magnitude worse. I hope you manage to get some rest, Kristin. I'll check in later on today (it's morning in the UK now) to see how you're both getting on.

Blessings to you both,


Mogs
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I have a lot of experience with both Cip and Mirt...so, you want to be very careful with Cyproheptadine as it can cause neurological issues in some cats if given over a longer period of time. It is used to stimulate appetite but typically for Cancer, CRF, PKD and other illnesses affecting appetite. Cpro is older and does work but harsher on the liver than Mirtazapine. I would perform blood work to check kidney values and also calcium/potassium levels to ensure they are up to par. Liver enzymes must be checked prior to giving these. The vet will typically just prescribe but having two of my fur babies been on both and my current 18yr old on mirtzapine, they just prescribe it. Mirtazapine is given once every 3 days (72 hours). Tests have indicated it is out of the body at that point but efficacy is typically down 90% after 36-48 hours. It must be given in a soft cat treat and handled with tweezers and you must not touch it with your fingers....Reason...they taste nasty. Even the outer shell is very bitter for cats. It might as well be peppermint flavor...so, what I have done in the past is take a small low carb treat and tweezer that small piece into a cat treat. The vet prescribed 15mg 1/4 pill once every 72 hours. However, the first time using it my cat was walking backwards and disoriented. Remember, this is a human grade pill used as serotonergic antidepressant (NaSSA) . Has found in most cats to stimulate the hunger center in the brain. I like this pill alot...only 1 small piece (1/32 or 1/64) of a tablet or if you quarter it then use 1/4 of that quarter. Typically, 10lb cat will be around 1/4 pill per vet (way too much) I've given this pill to 3 of my cats and all reacted way to harshly. If your cat cat taste it beyond the soft cat treat, use a pill popper found on Amazon for less than $10.00. still wrap that in a small piece of cat treat (but one that you wont use ongoing for other treats as the cat my associate that flavor with the pill popper or pill.

My pill was 15mg per...1/4 = 3.75 and 1/4 of that would be 0.94% of the 1/4 piece...It's better to give less than more...you can still achieve the effects you need.

 

We are only giving the Cyp to combat the symptoms of serotonin syndrome. The vet has me giving her a 4mg pill every 6 hours until symptoms seems to have resolved. I hope that is the right dosage, it's not like i can find much research on it. The mirt was a one time thing as was the bupenephiron. I had no idea that such a scary thing could happen with mirt.

 

Cerenia is very good for nausea in cats as well. I have used it...However folks...The God natural powder for nausea, mouth sores, indigestion for both upper and lower GI and suggested to use when switching foods is slippery elm bark- You can find this just about anywhere where vitamins are sold. I use 1/2 capsule daily but I do break it up into 1/4 twice daily...Its real easy to mix in wet food and some cats (2 of mine) ate it right from my finger (its sweet tasting)

 

Mirtzapine is safer, in my opinion from Ciproheptadine. Please work with your vet on this and if they are not knowledgeable...see about finding a vet that is familiar...advice is good, but given that they can only prescribe, best to get their thoughts first and tweek as needed (with their OK)

 

I think we are making progress on the serotonin syndrome, her pupils finally seem to be returning to a normal size. I just need to be able to watch her body movements more closely to see if the twitching/spasming has started to decrease. i cant wait until the office is open tomorrow just in case i need to take her in to be seen.

 

They gave her a cerenia injection the first time we went to the vet. Along with an antibiotic as a precaution, the antibiotic caused appetite loss, which is why we ended up giving her the mirta and a pain med because she has some arthritis in her back hips. That combo got us to where we are now. I am so tired, she is so tired. I just want the twitching/tremoring to stop so I can take her off ALL meds. From here on out I will be trying the natural options only , this is way too scary.

 

The latest studies show that 1/4 or 15 mg (1/2 of 7.5 mg) every three days is not best.
The Veterinary Teaching Hospital at Colorado State University therefore considers it safe to give mirtazapine every other day, but always start with ⅛ of a 15mg tablet. It usually takes effect pretty quickly, within a few hours, though it works more quickly for some cats.

Above from:
http://www.felinecrf.org/persuading_cat_to_eat.htm

 

Thanks Larry, this might be true, but even at 1/8 every other day, dosage may be high...id back down to a 1/16 every other day...

 

Now that i am looking at this with fresh eyes, I am certain they gave her too much. She is only a 12 lb cat and they gave her the larger dose, I am sure that did not help the situation at all.

 

Hi Kristin

My apologies for the delay in replying to you. I had hoped to post this yesterday evening but unfortunately I passed out from exhaustion (I have chronic fatigue problems ).

I have the following notes from Saoirse's journal of last year when she was given 1/8 of a 15mg tablet of mirtazapine (weight of cat - 10lb). They might contain something useful for you to use as a comparator:

------
9/8

18:00 - Mirtaz. 1/8 15mg tab - v hungry in <30 mins. Looking for food. Nauseated, can't eat. Called vet OOH. OK to give famotidine 2.5mg (stomach acid blocker) .
19:30 - impossible to pill - would have been badly bitten (completely abnormal). Made paste with pill & some food & put on paw. Ingested OK. Only managed <10g food so far.
21:30 - Food 24g Bozita,
00:20 - 18g (took hours). Ravenous.
00:45 - 26g Chicken breast & broth.
01:45 - 12g Chicken breast & broth.
04:50 -26g Chicken breast & broth, 2 more meals in timed feeder. (Chicken scoffed).

BAD REACTION TO MIRTAZAPINE: Bouts of overstimulated / hyper behaviour (could not settle; loud, non-stop purring - not a contented purr; pupils dilated to dinner plates; aggression - impossible to pill Saoirse; crazed, ravenous hunger; multiple odd vocalisations). Very worrying. Possible serotonin syndrome?

10/8

10:15-16g food. No nausea.
10:30 Seems mildy sedated, slightly spacey, walking slowly (mirtazapine?).
V dopey, low, lethargic in PM.
16:45 - 36 ml broth (slight dehydration),
17:30 - Slight nausea. Appetite waning. Lethargic. 18:00 Famotidine 2.5mg. 18:24 - able to eat again.

11/8

00:01 Mood slightly brighter and better in early part of day. Appetite good.
Lip-licking at 19:00 - Famotidine 2.5mg. Ate at 19:30 ok.

12/8

Seemed more comfortable in small hours. Ate all overnight timed feeds.
5:50. Appetite still very good.
10:15 Some lip-licking. Lifted food. Famotidine 2.5mg. Ate OK at 11:00.
Nausea back by lunchtime. Hungry but having difficulty eating again even with famotidine.
Late PM - vet visit. Tx: Cerenia

-----

The blue text is where I think the dose finally petered out, since the anti-nausea effect of the mirtazapine had worn off. Thankfully the worst of the severe side effects wore off in the first 12-18 hours after administration. All in all, it seems that it took about 90 hours for all of the effects of the single dose of mirtazapine to wear off.

I am very relieved to hear that Nova's pupils were returning to normal. I hope that her agitation and twitching has subsided as well. (When I was prescribed mirtazapine it made me very agitated and jittery but the agitation did lessen as the drug worked its way out of my system and there were no lasting after effects.) I'm glad that you've got good support from your vet. I think it would be a very good idea to get the vet to check her over physically today (Monday) as a precaution, and also to give you some much-needed peace of mind.

I hope that both you and Nova will have managed to get some rest by the time you read this, and that she is back to herself again. I really like your avatar picture; Nova's beautiful.



Mogs
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Hi Kristin,

Just checking in to see how Nova and yourself are getting on. I hope you both managed to get some bit of rest last night.



Mogs
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Hi Kristin,

How are things going with you two?



Mogs
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Hi,
I had to work today. I think as a whole she is doing better, much less twitching. She seems to have a broken bouncer right now , i.e.: she's having a hard time jumping on things. I gotta figure something out for her arthritis, I think she is finally starting to sleep more and more peacefully. I still feel guilty as all heck for all this.

 

I'm glad to hear that Nova's doing better, and that she's getting some peaceful snoozes. What a relief!

I can relate to the guilty feelings. I got an awful land when Saoirse had her bad experience on the mirtazapine and I was very angry with myself after the fact because I knew from taking the drug myself that its effects could be really nasty. However, like you I trusted the vet's knowledge and experience. Try not to be hard on yourself, Kristin. There was no way you could have known that Nova would have such a bad reaction. Try to take heart from the fact that you got her the antidote really, really fast and that she's recovering well. (Easier said than done, I know ... )

When you get a moment tomorrow let me know how Nova's getting on.


Mogs
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Nova seems to be doing MUCH better. I worked all day again today so I am not sure if her jumping is improving, but when I got home she actually trilled at me, she hasn't done that since before she got sick. She's also taken her old habit of harassing my picture/ribbon boards every night and I am not even mad that she wakes me up. The vet called today while I was at work so we shall see what she had to say, I am going to keep an eye on her for the rest of tonight to see if the facial twitching has stopped.

 

Hi Kristin,

Yay! What an encouraging update! I'm so pleased for you both. Isn't it just the best thing when they trill at you?!

Is Nova sleeping more restfully now, and have you managed to catch up a bit on your own sleep?


Mogs
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Yes, she is sleeping restfully. She wakes me up a lot harassing said ribbon boards though lol. Still a bit of facial twitching, but she's even back to snoring It is also nice to see her bright eyed again too.

 

But, but, but ... they've got ribbons on them! What's a kitty to do???!!!

 

It's great to hear you sounding happier, Kristin.

 

Thank you, Mogs. It is nice to not be insanely worried every second of the day that is for sure!