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Irritablity that meds haven’t touched

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So I posted on a topic a while back about a non sedating typical to help with irritability. This is a symptom that is a hallmark of a mixed episode- most often in the summer months. I have tried tons of stuff and I can’t seem to keep it down. Attempts (targeted at rage not overall) include benzos (ativan, Valium, klonipin) AAPs (PRN Zyprexa, abilify, latuda, PRN seroquel Geodon) stabilizers (Max Depakote, Max lithium, Max trieptal) typicals (hi dose trilafon; PRN Thorazine) and other stuff, often in combos. 

So despite my reservations about sedation, pdoc did a minor clozaril bump to try and shut things down. Not helpful and made me sleep in. So two weeks ago we ditched it, and he said let’s try and manage it with Xanax for a bit to see if we can avoid major changes because this cocktail has been the best I’ve ever been on, and there aren’t many obvious alternatives. 

So question- am I missing any obvious solutions? Risperdal and invega are out, and I’d really prefer a. PRN (pdoc too) cuz the last few major changes have seen shit hit the fan. I get terrible akathisia too, which is obviously a consideration especially for typicals, and since we know Thorazine can help I doubt he’d want to experiment with another (the Thorazine sedation makes taking it often impossible)

oh - also tried gabapentin, vistaril and beta blockers. ADs are probably not a good idea for me.

any alternatives I’m not seeing? 

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10 minutes ago, Melancholya said:

Lamotrigine? 

Thanks for the response! Unfortunately I am already on a large dose of that one, and my pdoc and I aren’t actually sure if it’s level of effectiveness, but it causes no side effects and I seem to be a bit stabler on it is it’s kind of a “what the hell” thing 

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3 minutes ago, Iceberg said:

Thanks for the response! Unfortunately I am already on a large dose of that one, and my pdoc and I aren’t actually sure if it’s level of effectiveness, but it causes no side effects and I seem to be a bit stabler on it is it’s kind of a “what the hell” thing 

Ahh sorry. :) other than that I have no idea. I have irritability / anger problems too and so far a low dose of sertraline and lamotrigine are keeping me level-ish. Could be better though. I hope you find something to help. Irritability is such an awful thing to experience. I always feel like a terrible person after my bad moods, which of course just makes everything worse. 

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Posted (edited)

I feel you @Iceberg. I understand where you’re at. Bumping my 10 mg dose of zyprexa to 20 mg is helping me somewhat but things could be better. I’m not sedated from it either, although I do take it in the evening. I’m just sick of being this way and sick of myself and sick of the damage I’m causing to my relationships/to others. What dose of zyprexa did you try PRN? I found lower doses didn’t touch it IME. Also the lower doses didn’t really help prevent or stop manic junk either that well for me. Would it be worth revisiting it at a higher dose and in the zydis form (fast acting)?

And risperidone is out for sure? I hear that’s supposed to be helpful. But I understand if it’s not an option. And I don’t have any experience with it and rage either so there’s that too. No experience there from me anyway. I mean I’ve been on it before, but back then rage wasn’t such an issue as it is now.

Edited by Wonderful.Cheese

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12 minutes ago, Wonderful.Cheese said:

I feel you @Iceberg. I understand where you’re at. Bumping my 10 mg dose of zyprexa to 20 mg is helping me somewhat but things could be better. I’m not sedated from it either, although I do take it in the evening. I’m just sick of being this way and sick of myself and sick of the damage I’m causing to my relationships/to others. What dose of zyprexa did you try PRN? I found lower doses didn’t touch it IME. Also the lower doses didn’t really help prevent or stop manic junk either that well for me. Would it be worth revisiting it at a higher dose and in the zydis form (fast acting)?

And risperidone is out for sure? I hear that’s supposed to be helpful. But I understand if it’s not an option. And I don’t have any experience with it and rage either so there’s that too. No experience there from me anyway. I mean I’ve been on it before, but back then rage wasn’t such an issue as it is now.

Thanks for weighing in cheese! Yes, risp is out. I was on zyprexa 5 PRN BID, plus 20 mg standing so I consider that a pretty fair trial. Plus zyprexa did sedate me, even low dose,  so probably tough to pair with cloz 

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Posted (edited)

i agree with @Melancholya, but failing that, how about adding tegretol? I think that's the only thing you've never tried. it might not be as sedating.

pregabalin? It's like a super gabapentin. maybe the gabapentin wasn't enough to make a difference. My MI is nowhere as severe as yours and i needed 400 at minimum to have any mood benefits, and 800-1200 (don't quite remember what) to completely quash depression. Like I haven't been legit depressed (though some minor blips) since I went to 1200.

Edited by argh
Needs more L
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Posted (edited)

I was going to suggest something like Gabapentin or Lyrica as well...both calming, but not "knock you out" like benzos or A/Ps. Another suggestion was Tegretol - I know @jt07 (RIP 😢) highly recommended that for mixed type agitation. Would lowering your Adderall temporarily help at all?

Edited by Blahblah

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yeah. i was thinking of @jt07 as well. RIP dude.

Celexa + Tegretol + abilify was his magic combo, IIRC.

I see that Celex and Abilify might be a no go for @Iceberg, but tegretol could be the ticket.

I'd vouch for the efficacy of two anticonvulsants at any rate.

We may want to start the summoning ritual for @browri and @mikl_pls

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1 hour ago, Blahblah said:

I was going to suggest something like Gabapentin or Lyrica as well...both calming, but not "knock you out" like benzos or A/Ps. Another suggestion was Tegretol - I know @jt07 (RIP 😢) highly recommended that for mixed type agitation. Would lowering your Adderall temporarily help at all?

My adderall dosing is pretty fluid, especially when not in school, so we already cut back on that. The problem is no adderall makes me sulky and sulky makes me feel shitty and that just keeps the cycle going. 

 

36 minutes ago, argh said:

yeah. i was thinking of @jt07 as well. RIP dude.

Celexa + Tegretol + abilify was his magic combo, IIRC.

I see that Celex and Abilify might be a no go for @Iceberg, but tegretol could be the ticket.

I'd vouch for the efficacy of two anticonvulsants at any rate.

We may want to start the summoning ritual for @browri and @mikl_pls

Tegretol did come up but we’ve been waiting because I’ve never had an AC combo that noticeably helped. I do kno that tegretol is different though. We are just being careful cuz my current combo make me “hazy” as is and don’t want to create new (worse) issues with sedation/motivation. It’s tough cuz this is mostly a summer thing so the ideal would be something that I could go on and come off in a relatively quick fashion. If symptoms get switched up in the next few months. I am obviously aware though that I’ve almost tried all the usual suspects so that goal may not be realistic

 

Also is tegretol rough on GI? 

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The thing about Tegretol is that you'd have to double your lamotrigine dosage to 800 mg! It would still have the same effect because carbamazepine increases clearance of lamotrigine. But just a note there. Carbamazepine can work wonders. There's also oxcarbazepine (Trileptal) if you didn't want one that would be so harsh with side effects. I believe carbamazepine can cause bone marrow suppression among other things. I do however see that Trileptal is in your signature as a past med.

I would not recommend Keppra because it has high liability of causing worse depression and "Keppra rage." Topamax might be a good addition to your cocktail, but as you said, I understand you want to be cautious with adding things. Zonegran might even be a good option, but I'm betting on Topamax.

A few typicals that I found to really help besides Thorazine are loxapine (Loxitane), trifluoperazine (Stelazine), and thiothixene (Navane). They may be a little sedating, but nowhere as much as Thorazine. Stelazine is my favorite, but Navane is rapidly becoming my second favorite. Stelazine with a benzodiazepine (especially Serax) is magic for anxiety and irritability in my experience. Loxitane on its own is probably even more effective than Stelazine with a benzo, actually. Loxitane smashed the psychotic depression I was in a few years ago at just 5-20 mg PRN.

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2 minutes ago, mikl_pls said:

The thing about Tegretol is that you'd have to double your lamotrigine dosage to 800 mg! It would still have the same effect because carbamazepine increases clearance of lamotrigine. But just a note there. Carbamazepine can work wonders. There's also oxcarbazepine (Trileptal) if you didn't want one that would be so harsh with side effects. I believe carbamazepine can cause bone marrow suppression among other things. I do however see that Trileptal is in your signature as a past med.

I would not recommend Keppra because it has high liability of causing worse depression and "Keppra rage." Topamax might be a good addition to your cocktail, but as you said, I understand you want to be cautious with adding things. Zonegran might even be a good option, but I'm betting on Topamax.

A few typicals that I found to really help besides Thorazine are loxapine (Loxitane), trifluoperazine (Stelazine), and thiothixene (Navane). They may be a little sedating, but nowhere as much as Thorazine. Stelazine is my favorite, but Navane is rapidly becoming my second favorite. Stelazine with a benzodiazepine (especially Serax) is magic for anxiety and irritability in my experience. Loxitane on its own is probably even more effective than Stelazine with a benzo, actually. Loxitane smashed the psychotic depression I was in a few years ago at just 5-20 mg PRN.

Trileptal was a massive fail. Topamax isn’t great for GI either right? I have to be careful about that. My doc and I have considered that as and add on and also for weight, but even the tiniest amount of “dopamax” would compound my nasty clozaril fog. Yeah keppra is out, and I’m guessing zonegran would be a reach for my doc. 

I looked up my cocktail and tegretol had 6 serious or significant interactions, 1 was the lamictal thing, but one said lowered Xanax effect and a few said screws with clozaril level. Normally I don’t get so concerned with that stuff, but my clozaril doses have been incredibly finicky.

heres my dilemma: if this is a short-term thing than is it better to just go with the benzos at higher doses and not the pain in the ass of trying typicals that are hard to find? I’m worried that we go through looking at typicals and pick one and it’s just the same effectiveness with bigger side effect profile. And like I said, akathisia is a big concern. On the other hand, I know the typicals might be good for reoccurring issues to keep my benzo intake down and possibly May more effectively target rage. Hmmm? 

 

 

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Posted (edited)
2 hours ago, Iceberg said:

My adderall dosing is pretty fluid, especially when not in school, so we already cut back on that. The problem is no adderall makes me sulky and sulky makes me feel shitty and that just keeps the cycle going. 

 

Tegretol did come up but we’ve been waiting because I’ve never had an AC combo that noticeably helped. I do kno that tegretol is different though. We are just being careful cuz my current combo make me “hazy” as is and don’t want to create new (worse) issues with sedation/motivation. It’s tough cuz this is mostly a summer thing so the ideal would be something that I could go on and come off in a relatively quick fashion. If symptoms get switched up in the next few months. I am obviously aware though that I’ve almost tried all the usual suspects so that goal may not be realistic

 

Also is tegretol rough on GI? 

I've never been on tegretol, so i cannot comment how it works on GI. From what i've read, while related to trileptal, has much greater efficacy.  You will need blood tests however.

Reading about ACs, it seems that only gabapentin and lamotrigine are the ones with the best cognitive profiles. Of course your YMMV as i've also read about lamotirigine causing cognitive issues (aphasia aside improved mine) and gabapentin being referred to as "morontin". IIRC Trileptal did follow the two. Tegretol was somewhere in there, but not as bad as topamax.

Edited by argh

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23 hours ago, Iceberg said:

Thanks for weighing in cheese! Yes, risp is out. I was on zyprexa 5 PRN BID, plus 20 mg standing so I consider that a pretty fair trial. Plus zyprexa did sedate me, even low dose,  so probably tough to pair with cloz 

Shoot. Too bad about the zyprexa not helping and being sedating. It would be tough to pair with clozapine you are right. 

What about low to mid dose Haldol? I used to take 5 mg three times a day when I tried it. I know they give it in injection form frequently to agitated patients along with or without a benzo in psych wardsor the ER. I’ve seen that many times. I don’t know if an injection of anything would prove more beneficial? Or prolixin? Just throwing some ideas out off the top of my head. Sorry if not helpful. 

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2 hours ago, Wonderful.Cheese said:

Shoot. Too bad about the zyprexa not helping and being sedating. It would be tough to pair with clozapine you are right. 

What about low to mid dose Haldol? I used to take 5 mg three times a day when I tried it. I know they give it in injection form frequently to agitated patients along with or without a benzo in psych wardsor the ER. I’ve seen that many times. I don’t know if an injection of anything would prove more beneficial? Or prolixin? Just throwing some ideas out off the top of my head. Sorry if not helpful. 

No I appreciate the input. I think that my pdoc would probably wait for psychotic symptoms to go for the haldol, and while I know it works, I think I’d be more comfortable keeping it as last line. 

I have had an injection for agitation in the ER before, but I’m not at that point yet cuz my regularly dosed meds keep me lucid enough to still manage to address issues. Also, potential akathisia (sorry I keep mentioning this) but I’ve had serious bouts of it on 3 separate occasions, the last of which my doc got worried it was so bad I’d become suicidal) We have talked about stelazine, but I doubt he will Rx it before trying the benzo approach 

 

 

 

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On 8/8/2019 at 11:47 AM, Iceberg said:

No I appreciate the input. I think that my pdoc would probably wait for psychotic symptoms to go for the haldol, and while I know it works, I think I’d be more comfortable keeping it as last line. 

I have had an injection for agitation in the ER before, but I’m not at that point yet cuz my regularly dosed meds keep me lucid enough to still manage to address issues. Also, potential akathisia (sorry I keep mentioning this) but I’ve had serious bouts of it on 3 separate occasions, the last of which my doc got worried it was so bad I’d become suicidal) We have talked about stelazine, but I doubt he will Rx it before trying the benzo approach 

 

 

 

Gotcha. Sorry for not helpful input. I hope you find something that can help I know how damaging this can be. I just looked at a Facebook “memory” from 2012 and I was raging at some poor restaurant server back then even. Maybe anger is a bigger symptom for me than I originally thought. I thought it was a new problem but that isn’t so. Ugh. Kind of breaks me. I always considered myself to be kind hearted. At least I was before I got sick with MI’s. 

Anyway, I’m so sorry you are dealing with this. It’s such a nasty symptom and IME pdocs don’t take it seriously enough. 

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Posted (edited)
On 8/10/2019 at 8:34 AM, Wonderful.Cheese said:

Gotcha. Sorry for not helpful input. I hope you find something that can help I know how damaging this can be. I just looked at a Facebook “memory” from 2012 and I was raging at some poor restaurant server back then even. Maybe anger is a bigger symptom for me than I originally thought. I thought it was a new problem but that isn’t so. Ugh. Kind of breaks me. I always considered myself to be kind hearted. At least I was before I got sick with MI’s. 

Anyway, I’m so sorry you are dealing with this. It’s such a nasty symptom and IME pdocs don’t take it seriously enough. 

If I recall, @jt07's combo did include Tegretol+Lamictal and Celexa+Abilify. So maybe there is something to anti-convulsant combos. However, I shied away from them myself for the same reasons. AC combos caused more cognitive issues. A combo of a strong AC with a low dose of an AAP was what did it for me.

As for carbamazepine's effect on the GI, it may cause nausea from what I understand. I've only tried carbamazepine briefly, but I took the Equetro brand name medication. You can get the same thing from generic Carbatrol, but insurance companies will generally cover Equetro as a preferred brand because only that formulation of carbamazepine was actually APPROVED for bipolar disorder. The generic carbamazepine tablets were never approved for it. However, Carbatrol was a capsule formulation of carbamazepine with a 3-stage bead mechanism whereby it would essentially provide two divided immediate release doses via two different kinds of beads, one dissolved immediately, the other dissolved when it reached a certain point in the small intestine, and then there were slow beads that created the XR mechanism.

The controlled release mechanism described above made Carbatrol slightly more tolerable than Tegretol XR and quite a bite more tolerable than Tegretol IR.

The only reason I quit carbamazepine was because it made me hear everything a semi-tone lower. As a musical person that was a deal breaker because I would hear myself in the correct pitch but hear everything else flat. I couldn't sing anymore to save my life and it was really distressing.

However, the time that I was on it, it was quite effective in substitute from valproate. I don't think I really had a good opportunity to feel it out though because carbamazepine becomes more tolerable with time as it starts inducing its own metabolism (and that of other drugs as you've seen from the interaction checker)

Edited by browri

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In follow-up to my last post I pulled out my Psych PDR written by Dr. Stephen Stahl, and he does make note in the dosing tips that many of the side effects experienced can be lessened by taking a controlled release formulation of carbamazepine:

  • "Controlled release formulations (e.g. Equetro, Carbatrol) can significantly reduce sedation and other CNS side effects"

There's a key to this quote though. Notice that Tegretol XR isn't mentioned at all in his examples of controlled release formulations. Equetro and Carbatrol were both the CAPSULE formulations, whereas Tegretol XR and its generics are tablets. The Tegretol XR formulation (and generics) uses an osmotic delivery system to absorb water from the GI tract and then disperse the contents of the pill as it transits through the GI tract. These delivery systems work, but they aren't perfect and they can sometimes be unpredictable from person to person. They can sometimes leave the shell of the pill in the stool as well. This is also why the XR tablets are "punctured" in a way.

As I said in my last post, Carbatrol (and its generics) as well as Equetro use a 3-bead delivery system. In each capsule, 25% of the dose is immediate release beads that dissolve the instant they hit water (in the stomach), 40% of the beads are extended release dissolve over time (8-12 hours), and 35% of the beads are enteric release meaning they dissolve slowly in the small intestine once they've reached the appropriate pH. This tri-phasic delivery system can reduce sedation, ataxia, nausea, and vomiting for many who cannot tolerate the tablets. It also provides for more consistent blood levels with fewer peaks and troughs, which could explain the reduction in side effects.

While the hearing side effect was a deal breaker for me, I found Equetro to be otherwise quite tolerable and very effective and I only made it to maybe 400mg.

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Was also just reading through @mikl_pls's response and totally forgot about the idea of typical augmentation to an atypical. If clozapine isn't "clozing" (hehe I made a funny) the gap, then I would say it's high time for augmentation with a typical AP PRN. Specifically loxapine would be my recommendation and trifluoperazine because I haven't tried it but @mikl_pls describes it as his "brain glue".

For loxapine, it's likely something you would take 5-10mg PRN for agitation/rage. It does take 30-60 minutes to fully kick in though. That would be the only downside. You could take up to 25mg during the day but after 10mg you're liable to just go right to sleep. Typically (hehe I made "punny"), you would use 10mg as a nightly dose and 5mg during the day as needed for agitation, but you don't generally want to go past 25-50mg in a day because then you're in EPS Land (akathisia and other unpleasantries).

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