Anti-psychotic properties of the TCA Trimipramine

[paranoid android]

Okay i am not quite sure if this is the right foruum for this so fel free to move this if you want.

I have taken Trimipramine a few times before when the major depression part of my Bipolar disorder got really bad. A few times i was put on a lowish dose of say 50-75mg's of trimipramine with the anti-depressant my doc feels most comfortably to Bipolar patients which is Bupropion. And yes i know taking 2 different anti-depressants if you have Bipolar is asking for it but i've never had a problem with it. I find Bupropion to work great at treating SAD and the can't stay awake, extreme fatigue type of depression but it really get's bad Bupropion or even Bupropion mixed with Lamotrigine and Quetiapine doesn't completely pull me out of the funk. Adding Trimipramine to my med combo or taking it as the sole anti-depressant does tend to work plus it actually helps me get what i would call restful sleep just like Amitriptyline another Tricyclic that helped me did.

I have read that along with it's anti-depressant properties it also act's as a mild Anti-psychotic. In one trial i read it didn't seem as potent or work as good as the moderate potency typical Anti-psychotic Perazine although it did demonstrate anti-psychotic activity. I was wondering how potent of a anti-psychotic it is compared to weaker anti-psychotics such as Methotrimeprazine and Periciazine.

 

[Kittycat5]

Not much info out there as these are fairly uncommon drugs. That study of trimipramine vs perazine, at least according to its authors, only concludes they couldnt find dosing equivalent between the two, not necessarily that perazine was superior. Trimipramine seems to have a very similar pharmacolgical profile as clozapine and saw a small paper showing it may be only slightly less effective than clozapine for schizophrenia. But the doses were several hundred mg daily in both the study you read and I believe the clozapine one as well, which is higher than the normal antidepressant dose. Probably just not enough info out there to make adequate comparison between trimpramine and phenothiazine or other typical antipsychotics.

 

[paranoid android]

Trimipramine is used quite abit here by some doctors. My doctor prefers it over other Tricyclics actually. Besides Amitriptyline and Bupropion it's the only anti-depressant that's never triggered mania in me. But ya i couldn't find much info on it at all and was just wondering if anyone had read better studies on it.

 

[serotonin2A]

It makes sense that it wouldn't trigger mania if it has antipsychotic properties. it has a high ratio of 5-HT2A to D2 blockade, which is the signature for an atypical antipsychotic. But it's antipsychotic efficacy is probably not high enough for that to be the primary indication that it is used for.

 

[dopamimetic]

Did you actually have had psychotic episodes, or is it 'just' about mood swings - depression and (hypo)mania? Have you Bipolar I or II / rapid cycling or slow phases? I don't really like this symptomatic pigeonholing as everyone's mind is different but it's required to get a base to work on..

D2 blockade is generally bad unless you're really out of this world psychotic in my eyes.. but yes, the 5-HT2a blockade of trimipramine might be of great benefit, this could actually make a better antipsychotic for some (many?) than dopamine antagonism! (Just speculating based on some scientific evidence and my strange cognition, as usual )

An interesting fact is that bupropion modulates glutamate (and glutamate is more involved in mania as even dopamine - possibly - or at least equally) in rats it decreases glutamate output - but rats also self-administer bupropion due to differing metabolism & it could well be that in humans it does something different. It's a strange kind of locked-down cathinone that should be a more or less potent (S)NDRA like 3-CMC etc. but it isn't ... I've managed to 'unlock' it by accident, but that's another story, just that it confirms some of my theorizing
At least it seems to be somewhat for sure that the NDRI action of bupropion when used alone is too weak to be the key mechanism.

But if I understand you correctly, you're currently taking at least four psychopharms ...? I know it's usual practice to 'augment' one with the other, and indeed I agree that often a combination of synergetic low-dosed agents can be better than one high-dosed one, but this needs to be established carefully... I don't want and can't play doctor at all, just my 2 cents as I've gone through half a pharmacy by myself... (and luckily I'm still able to do things like write such postings ... I've met far too many people - some younger than me, and some with higher education - who were completely destroyed by adverse effects and all that.. don't want to scare you, that's the worst case always but it happens..)

Good luck

 

[paranoid android]

Right now i am only on 200mg's of Lamotrigine a day and 6mg's a day of Clonazepam. I haven't had a manic episode in ages so i am taking a break from the Quetiapine and as my depression wasn't bad until this week i haven't been taking Bupropion either. I have been diagnosed as having Bipolar 1 disorder because of the intensity of the mixed states i get and the fact that i get full blown mania. I have had a few psychotic like episodes because of Bipolar but only when my Mania, Mixed state or sometimes depression get's really awful.

 

[dopamimetic]

Hey android

So well.. then I'd definitely go against the neuroleptics / dopamine antagonists. This is an opinion not everyone shares, but in my eyes they do more bad than good (had neuroleptic malignant syndrome twice.. this is rare but serious). Quetiapine is one of the least 'serious' antipsychotics though, in low dosages it's mostly an antihistaminergic and anti-adrenergic which makes it a sedative. But these properties you can get without the bunch of other effects & side effects with e.g. clonidine (a centrally acting a2 auto receptor agonist --> leading to lowered norepinephrine, more or less the same net effect as adrenergic blockade), makes a good sleep aid (and possibly anti-manic- can't say, but could be worth a try!)

5-HT2A antagonism is a promising mechanism for antipsychotics without many of the bad side effects.. so Trimipramine could really be worth a try.

Would you mind to describe the 'quality' of these psychotic-like episodes? This is hard to put in words maybe, but things like ... is there amnesia, delusional thinking / acting, hallucinations, feelings in any way from anxiety up to 'mystical' experiences..? This could help to get an imagine of the underlying mechanisms.. just plain guessing of course, based on own experiences and education, but then again sometimes I had the feeling that the one or other doc knows even less ..

Do you feel that the Lamotrigine helps you to stabilize against mania, depression or both - sometimes, or rather not really? Do you take the Clonazepam for sleep or during the day?
Sorry for all the questions, just say if it's inappropriate..