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Could Clozapine (Clozaril) be making me more aggressive?


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After spending an extended period of time on a maxed out dose of seroquel (1,000mg), my pdoc is pushing to replace it completely with clozapine. The idea being that she slowly decreases the former while working on increasing the latter. I started on 100mg/night of the clozapine last Wednesday. Over the weekend I noticed that I'm starting to react aggressively to everything from apparently harmless comments from friends and family members, to other drivers on the roads. By "aggressively" I mean taking offence at everything, snapping unnecessarily at people and doing everything possible to cause an accident when I feel that another driver is behaving like an idiot. Even when sitting here in my livingroom on my own I'm grinding my teeth and wanting to throw a punch at someone or something.

This isn't PMS, and it's definitely an increase on my "normal" levels of irritability and general crankiness. Since the only thing that's changed in the last 5 or 6 days is a small decrease in seroquel and the addition of the clozapine, I have to ask whether the clozapine could be causing this. I'm tempted to call my pdoc and ask for a short diazepam script, but I see her again on Wednesday and in any case, I'm not a fan of taking drugs to counteract the effects of other drugs. I've btdt in a big way, particularly in the first half of this year, and it wasn't a pretty sight (ended up with my being required to take 16 pills a day, and I eventually wound up in hospital vomiting up blood).

AND this is all completely aside from all the other hassles and side effects of clozapine. I'm not thrilled at the prospect of weekly blood counts. Clearly pdoc is starting to view me as a treatment resistant patient... and hey, that pisses me off too.

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If my Seroquel gets lowered at all or I miss a dose I get very agitated verging on aggressive. Perhaps it is the lowering of the Seroquel without the Clozaril having kicked in to compensate?

If a benzo would help as a stop-gap measure I'd personally be asking for it. Even a few days of agitation/aggressiveness can have a big impact. Good luck & I hope you sort something soon.

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Miab, it's possible that the clozapine could make you more aggressive, but it's very unlikely.

It's far more likely that, as Generica suggested, the reduction in Seroquel is the issue. I see it's at 800 mg in your signature line? That's actually a pretty big drop.

If you could reach your psychiatrist and ask if you could stay on the full-dose Seroquel 'til the clozapine's at a therapeutic dose... that might make a difference. When clozapine works, it's amazing. When it doesn't work, meh. And the weekly blood counts are annoying as hell, I agree, but they're not going anywhere (well, until you're at dose for 6 months with no significant fluctuations in white count.) It's a testament to clozapine's efficacy that it's still around despite the need for that level of monitoring.

They both go through the same metabolic pathways, IIRC, but clozapine does not increase clearance of Seroquel to the kind of dramatic degree that I remember hearing about it.

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Thanks very much for the responses. I think the idea that this is all being caused by suddenly dropping from 1000mg of seroquel to 800mg is probably correct. I went for a long, fast swim this morning in the hope that it would ease the feeling that I need to yell and scream at everyone, but it didn't.

Anyway, my pdoc appointment is tomorrow (can't get hold of her today, as it's a public holiday), and I'll ask her outright if I can just stick at the original seroquel dose until the clozapine has been increased. She's aiming at 600mg of that.

thanks again

M

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Hi,

I think you and i have been at 1000mg seroquel for a similar amount of time. why the change? (you dont have to answer if its too personal).

I went down to 900mg for an "experiment" and felt like the law of gravity was going to stop working and i'd float off my bed.

(i also have a nasty cold/sickness that could be messing everything up, too.)

I dont have any knowledge of clozapine.

I hope that this change is a positive one for you,

db

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I'm glad you're seeing your pdoc tomorrow. Hopefully it'll help sort this out.

600 mg clozapine sounds high too, seems to me........

i think that tapering Serequel while titrating Clozapine is usually how it's done, but maybe the 200 mg drop was too much too fast. My pdoc has also told me that Clozapine should be titrated by 50 mg/day, so I'm likely not being any help here.

As for the weekly blood tests- ya, that sucks, but it does go to every 2 wks in 6 mths, and after a while it can even go to once/mth if all is well with your white blood cells.

hope to hear how it goes...

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The usual first "plateau" is around 350-500 mg, but it's pretty common for people to be in the 600-700 mg range or a bit higher. ~600 mg is considered a full therapeutic trial dose by my psychiatrist.

Miab, I'm sure you've found lots of info already, but the Mylan clozapine page has a good general overview of how the registry works, etc. It doesn't seem to vary much from country to country (or registry to registry.)

Another thing to watch out for, which I forgot earlier: Clozaril is sorta kinda famous for inducing orthostatic hypotension; Seroquel does this sometimes. The two together = more hypotension. So be aware of that as you stand up, and if you have a lot of dizziness, call your doc.

Going up slowly on the clozapine may reduce the problems with hypotension. It drags out the period of blood draws, but... you don't fall down when you stand up.

Clozaril really did save my cousin's life. It's what let him get back into grad school. It's an amazing drug. It's just a tricky one. If it weren't for the agranulocytosis, seizure risk, hypotension, sedation, etc., I'm sure it would be much more popular....

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Clozaril really did save my cousin's life. It's what let him get back into grad school. It's an amazing drug. It's just a tricky one. If it weren't for the agranulocytosis, seizure risk, hypotension, sedation, etc., I'm sure it would be much more popular....

It really did save my son's life, too. I agree- an amazing drug. His only side effects are drooling and sedation. He's been able to pull the doseage back to 300 after 2 1/2 yrs and blood tests only 1 per mth. Pyschosis remains but is manageable and sedation is also manageable for him on this doseage. Any problems, he can up the dose and get immediate results.

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Clozapine/clozaril is an amazing drug. However it is meant to be a "salvage" or last resort medication. It is supposed to be used when all else fails, due to its potential fatal side effects which are monitored by lab work. I am concerned about the 600mg dose. I know a good amount about clozaril since I used to work at a community mental health agency that treated 450 people, and I dealt with many many people on clozaril. I also now work at a group home with 3 people on it. Just because you had to go to the max dose of seroquel does not mean you need 600mg of clozaril. I recently had a client in the hospital for severe psychosis, who had formerly lived at the state hospital for over 20 years. The psychiatrist was comfortable discharging her on 200mg of clozaril. The only people I have known to take that much or higher have been very psychotic before getting that dose. Everyone eliminates it at a different rate. It should only be increased if it isn't working or if the actual blood serum level of it is low. So just go slowly and don't take more meds than you need. (Disclaimer: I'm not a medical doctor)

I just noticed that your diagnosis is bipolar. Do you experience psychosis? If not I'm not sure why you are being given clozaril. It really is too serious to be used to treat only mood issues. I've never seen it given to someone with bipolar and no psychotic symptoms.

I also agree that the decrease in seroquel is causing the agitation. A good PRN should help you through this cross titration period. Good luck!

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However it is meant to be a "salvage" or last resort medication. It is supposed to be used when all else fails, due to its potential fatal side effects which are monitored by lab work. I am concerned about the 600mg dose. I know a good amount about clozaril since I used to work at a community mental health agency that treated 450 people, and I dealt with many many people on clozaril. I also now work at a group home with 3 people on it. Just because you had to go to the max dose of seroquel does not mean you need 600mg of clozaril. I recently had a client in the hospital for severe psychosis, who had formerly lived at the state hospital for over 20 years. The psychiatrist was comfortable discharging her on 200mg of clozaril. The only people I have known to take that much or higher have been very psychotic before getting that dose. Everyone eliminates it at a different rate. It should only be increased if it isn't working or if the actual blood serum level of it is low. So just go slowly and don't take more meds than you need. (Disclaimer: I'm not a medical doctor)
Well, yes and no.

Clozapine is gaining more acceptance and it is being looked at for schizoaffective disorder and 'refractory' manic-depressive illness. More clinical guidelines are suggesting that it be used earlier in the treatment process. Quite a bit coming out of Canada on this lately. Some of this is because of the reduction in suicidality in schizophrenia, but more of it is just the plain clinical efficacy.

Miab's post doesn't necessarily indicate she's going to be taking 600 mg of clozapine; her psychiatrist may be 'aiming at' that as the highest end, but most prescribers are going to stop at desired effect, as per standard medical practice. There is, obviously, huge variance in dosing, with low-dose augmentation being one option, and great whacking doses being another. Yes, everyone does eliminate it at a different rate. Thanks for explaining that.

I've seen folks who were floridly psychotic who needed a 50 mg augmentation dose on top of their (whatever antipsychotic they were taking), and I've known people with refractory mania who needed 800 mg, and I've known all sorts of people in between. It's a really interesting augmentation option. Had they been using it that way when my cousin was started on it, they probably would have combined it with his other rx...

Er - 'salvage' medication? What an... interesting phrase. I think part of the shift towards using clozapine earlier is to avoid things getting to the point where patients (we) are thought of as requiring 'salvage.'

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Thanks for the responses. I saw pdoc yesterday and she agreed to slow down the seroquel decrease - she said she's happy to do it over several months if that's what it takes to make a smooth transition to the clozapine.

I think you and i have been at 1000mg seroquel for a similar amount of time. why the change?

I've had a few breakthrough episodes and pdoc reckons that seroquel isn't doing its job anymore. I'm not thrilled... she's right about the fact that I should be a great deal more stable than I am, but I've always seen it as my "magic drug" and I'm pretty twitchy at the prospect of letting go of it.

600 mg clozapine sounds high too, seems to me........

According to my pdoc the highest dose is about 800mg, so 600mg is still within a reasonable range.

Another thing to watch out for, which I forgot earlier: Clozaril is sorta kinda famous for inducing orthostatic hypotension; Seroquel does this sometimes. The two together = more hypotension.

thanks, I hadn't seen that. I'm going for my blood draw this morning and while I'm there I'm going to ask them to check my blood pressure, which is typically low in any case.

because you had to go to the max dose of seroquel does not mean you need 600mg of clozaril.

Without meaning to sound pissy, if you look at my original post the question was NOT about the amount of clozapine, it was about whether or not it could be affecting my mood negatively at this early stage. I'm not prepared to debate the clozapine dosage decisions made by my pdoc.

Do you experience psychosis?

yes.

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hi miab,

i, too consider seroquel my "magic drug." its definitely been a good one.

today i got some bad news on other parts of my body and im re-evaluating everything. i hear you on not wanting to let go of seroquel.

cbl wrote:

However it is meant to be a "salvage" or last resort medication.
good god, what happens if clozaril doesnt work? what's the response? slitting wrists?

db

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I am following this thread with interest as every time I go to see the shrink he just bangs on about clozaril but it would kill my mother if I went on it (she wants to wean me off olanzapine, topamax, prozac and inderal in the New Year) She has all access to the meds - nowt I can do about it!

good luck!

blackbird x

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Here, Clozapine is indeed a 'last resort' AP. Not only the serious health risk, and risk of non-compliance because of the blood tests, but it's horrendously expensive. If he [or we] had to pay for it, my son would not have it and be dead for sure. His psychosis is extreme and continuous, and nothing could touch it like this stuff.

Also, it acts so quickly! Titrating up 50 mg/day from nothing to 350 brought him back to sanity in just over a week during his last episode and for the first time was not hospitalized.

Yet as powerful as his psychosis is, he doesn't need any more than that [stays mildly psychotic on 300 to avoid being a zombie] to have quite a good quality of life.

I hope you won't need a high dose, miab. Wishing you well with this....

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If I could find something that could touch even one tenth of my psychosis, I'd be the happiest woman alive. But my mother would die of a heart attack if I took clozapine so I have to keep refusing it even though it's all the shrink bangs on about these days when I see him.

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Well, lithium has always given me sandpaper mouth, so you'd think I'd be happier with this new and exciting side effect. Not really though - it doesn't actually get rid of the thirst. Maybe because I'm drooling too much for any of the excess saliva to make a real difference. (geez, I can't think of another place on the net where I can unashamedly post about dribbling all night ;) )

Here, Clozapine is indeed a 'last resort' AP. Not only the serious health risk, and risk of non-compliance because of the blood tests, but it's horrendously expensive

That's interesting Apterix - I've been given a generic, and even without the contribution of my med insurance, the clozapine works out as cheaper than my lithium (which is also a generic and has a very low price). I'm perpetually puzzled at how different things are from one country to another. (eg a lamictal generic has been available here for several years; there are at least 5 zolpidem (ambien) generics here, and all were around for years before the generic hit the US; seroquel XR is available there but not here... the list goes on)

Thank you for your good wishes - they're much appreciated.

sorry, I missed this first time round:

But my mother would die of a heart attack if I took clozapine so I have to keep refusing it even though it's all the shrink bangs on about these days when I see him.

if it's okay to ask... why should your mother's reaction play such a controlling role in your treatment? At some point most of us will reach the stage when we have to be prepared to do whatever it takes to deal with our illness.

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Okay, after a few days on 150mg I no longer feel like killing everyone in sight, and I'm getting approx 6hrs of sleep a night, which is a HUGE thing for me. On the other hand, the drooling is so repulsive (I mean seriously, my pillow is thoroughly wet by the time I wake up in the morning, and my hair's all damp and knotty), and I'm really not sure I'm prepared to live with that. I didn't know it was possible for one person to produce so much drool. Yes, I know that sounds petty, but at the end of the day doesn't it boil down to what I can and can't tolerate?

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