Imipramine or Clomipramine

[WiseMonkey]

Hi Wisemonkey thanks for validating that I’m not alone with SSRI’s leaving me climbing the walls, albeit Peroxatine initially was a gift from god. But then it turned round and bit me real bad !!!! I then easly tolerated venlafaxine....Now however my body and brain are saying no way and only by talking Pregabalin along with Diazipam am I managing !!!!

Good to hear that the body can reject SRI meds if you keep going on and off them. My understanding is that this is much less of an issue with TCA’s

Thanks and can I ask which was the worst component of your illness ‘Anxiety’ or ‘Depression’ ???? Thank you John

I was put on TCA because they were frontline meds for depression back in 1988. SSRI's had only been on the market for a few years and weren't commonly used. I had a few bouts of depression and each time Doxepin (TCA) helped me.
I have an overactive immune system (due to autoimmune issues) so they seem to suit my body. Doxepin and Amytriptyline also have high antihistamine qualities which helps with mast cell issues and they also have a sedating effect which helps with sleep.
When my father had depression, in the 1990's the Dr prescribed him Doxepin as it had worked well for me, so there may be a familial link to a particular AD that suits.

For me, anxiety comes first and is the worst part of it all because of the physical symptoms it produces. Mine always stems from a health issue. If the anxiety can't be addressed then it turns into depression where you body slows down and you feel like you're in a dark tunnel where my emotions flatline and I can't feel much of anything! The good news is that as I've got older I've had less depression, my anxiety still fluctuates but I'm stemming it better

[SideFX]

I was put on TCA because they were frontline meds for depression back in 1988. SSRI's had only been on the market for a few years and weren't commonly used. I had a few bouts of depression and each time Doxepin (TCA) helped me.
I have an overactive immune system (due to autoimmune issues) so they seem to suit my body. Doxepin and Amytriptyline also have high antihistamine qualities which helps with mast cell issues and they also have a sedating effect which helps with sleep.
When my father had depression, in the 1990's the Dr prescribed him Doxepin as it had worked well for me, so there may be a familial link to a particular AD that suits.

For me, anxiety comes first and is the worst part of it all because of the physical symptoms it produces. Mine always stems from a health issue. If the anxiety can't be addressed then it turns into depression where you body slows down and you feel like you're in a dark tunnel where my emotions flatline and I can't feel much of anything! The good news is that as I've got older I've had less depression, my anxiety still fluctuates but I'm stemming it better

Thank you WM I’m the same in that I follow the SAD acronym Stress then Anxiety then Depression...Usually in that order !!!

I’m glad you have found a suitable med and stuck with it - See that’s we’re I went wrong I’ve found medications twice and come off em, only to lead to intolerable effects, when trying to get back on and now I feel exhausted by all med changes. But don’t want to live like this

In the words of Paul Weller ‘Afraid of living and scared to die’ ...Have you ever tried an SSRI ??? Sorry for quizzing people, but I want to make a wise informed decision. When I’m in a position to take that risk Thank You very much John

[WiseMonkey]

I've also started on Choline/Inositol twice a day as I have issues with my methylation cycle, it's helping with sleep too.
250 mg/250 mg

[SideFX]

Bruxism is a relatively common side-effect of ADs, but anxiety can trigger it too.



SSRIs may not be doing what you think they do: Serotonin - The 'chemical imbalance' myth



Yep, you can't really judge a med under that circumstance. Duloxetine is the pick of the common SNRIs because it actually is one, but it can produce severe side-effects at the beginning. The less common SNRIs milnacipran and levomilnacipran may be the pick of the bunch, although data is scarce.



They all have their individual box of tricks which they use on everyone and soon get lost when the patients don't do what is expected of them by failing to get better. That's when many go into poly-pharmacy mode. Plus, unless they are offering therapy isn't it actually "all about the meds"?



Don't let them get away with it. You're paying for their time, directly or indirectly, so insist on getting your money's worth.

I'm not surprised at the refusal to prescribe MAOIs. Unless they are in the sixties they've likely never been exposed to them and the data on MAOIs is way out of date. Unfortunately, there is no pressing reason for the powers to be to change this. Ken Gillman is about the only one trying to drum up interest and he'll almost certainly fail, just as his efforts to correct the BS about serotonin syndrome has mostly fallen on deaf ears among the WHO, FDA, MHRA, TGA, etc, decision makers and med journals.



It was the first med I was put on for panic disorder back in early 1987. No SSRIs back then, which was fortunate as they don't mesh well with my biology. I was on it, off and on, for about 8 years mostly at 300-350mg/day (which would horrify most psychiatrists these days, but the bloke that developed it took 1,000mg/day for a while without issue - that was back in the good ol' days when drug developers were their own guinea pigs). It worked well and the only side-effects of note was dry-mouth and moderate sexual dysfunction, plus a slight head shake at 350mg which seemed to be only apparent to me. I switched to dosulepin in ~1996 because the common wisdom of the time was that it was the safest TCA and produced fewer side-effects. Turns out the first was 210% wrong, it is the most cardio-toxic AD by a significant margin, but the second is true. I have no discernable side-effects.

Do you know what your right I’ve paid into the NHS all my life and never asked anything back from it, until recent years and I totally agree that Pdocs go with what they know and don’t like you challenging any decision.

The thing I don’t understand is how noradrenalin has an effect on PD and Anxiety??? As it’s linked to the adrenal system. I’m struggling to get my head round that bit and why did I do so so well on Peroxatine in response to my first episode

Thanks for all your wisdom and pure nuggets John.

[panic_down_under]

Do you know what your right I’ve paid into the NHS all my life and never asked anything back from it, until recent years and I totally agree that Pdocs go with what they know and don’t like you challenging any decision.

They all delude themselves into believing they've been elevated into the realm of the not so minor deities, John. Like most self-promoted gods in their own tea breaks they all have feet of clay (some are even nuttier than their patients too, ime). You're doing them a favour if you burst their bubbles by reminding them they are in fact just the hired help. Everyone needs a good dose of reality from time to time.

The thing I don’t understand is how noradrenalin has an effect on PD and Anxiety??? As it’s linked to the adrenal system.

Nope. Noradrenergic (NA) ADs work by the same mechanism as the serotonergic (5-HT) ones, stimulating the growth of new hippocampal brain cells, possibly by their effect on gene expression. The genes affected seem to differ between NA and 5-HT reuptake inhibitors, but the end result is the same. Or it could be something completely different. That neurogenesis is the mechanism which produces the therapeutic response is pretty much settled science, how it is achieved is still poorly understood.

I’m struggling to get my head round that bit and why did I do so so well on Peroxatine in response to my first episode

Because tolerance wasn't then a factor. It can develop with ADs just as it may do with BZDs, especially with SSRIs. It happens less with SNRIs, TCAs and MAOIs, perhaps because their multiple lines of 'attack' make adaption more difficult. Why stopping and restarting a med should increase the likelihood of tolerance developing is a mystery. One that may never be solved because I don't think anyone is looking. Few researchers seem to be even aware it is a problem. And even fewer psychiatrists.

[SideFX]

They all delude themselves into believing they've been elevated into the realm of the not so minor deities, John. Like most self-promoted gods in their own tea breaks they all have feet of clay (some are even nuttier than their patients too, ime). You're doing them a favour if you burst their bubbles by reminding them they are in fact just the hired help. Everyone needs a good dose of reality from time to time.



Nope. Noradrenergic (NA) ADs work by the same mechanism as the serotonergic (5-HT) ones, stimulating the growth of new hippocampal brain cells, possibly by their effect on gene expression. The genes affected seem to differ between NA and 5-HT reuptake inhibitors, but the end result is the same. Or it could be something completely different. That neurogenesis is the mechanism which produces the therapeutic response is pretty much settled science, how it is achieved is still poorly understood.



Because tolerance wasn't then a factor. It can develop with ADs just as it may do with BZDs, especially with SSRIs. It happens less with SNRIs, TCAs and MAOIs, perhaps because their multiple lines of 'attack' make adaption more difficult. Why stopping and restarting a med should increase the likelihood of tolerance developing is a mystery. One that may never be solved because I don't think anyone is looking. Few researchers seem to be even aware it is a problem. And even fewer psychiatrists.

Thanks again Ian, even more nuggets to digest...My bruxism started from day one of brintellix and I have never experienced it before (So the med is causing it for sure, along with other SideFX)

My Pdoc is under the impression that bruxism is a result of too much serotonin and that’s garbage, as I’ve asked Ken Gillman that direct question and his response was a huge NO....Therefore messing with Mirtazipine dosage will have absolutely no effect on my bruxism!!!! This makes me question my pdoc’s real understanding of medication and its also scary that he diagnosis patients and dishes out stuff he’s considerably ignorant of

I do get the diurnal variation in my anx/dep....So that follows the typical pattern of biology for me and I’ve spoken with my Pdoc, who doesn’t really agree that a successful med would resolve it !!!! And thinks that it could take me 5 years to recover...Now that is pure horse shit and again garbage !!!!!

I am worried about the withdrawals from brintellix when I cross taper to imipramine and really worried that it could all go horribly wrong and end up in hospital again. Any advise on these matters would be greatly appreciated thank you John

[panic_down_under]

My Pdoc is under the impression that bruxism is a result of too much serotonin and that’s garbage, as I’ve asked Ken Gillman that direct question and his response was a huge NO....

Too much/little serotonin, probably not, at least not directly. It is more likely an indirect suppression of dopamine transmission by serotonin activity. The 5-HT1a receptor agonist buspirone (Buspar) is often prescribed for SSRI/SNRI induced bruxism. It is thought to work by enhancing dopamine transmission and increasing dopamine release in the frontal cortex. Buspirone may also alleviate other SSRI/SNRI side-effects such as sexual dysfunction and boost the effectiveness of these ADs. Unfortunately, you probably won't get it on the NHS. Seems they're not fans.

Therefore messing with Mirtazipine dosage will have absolutely no effect on my bruxism!!!!

Mirtazapine also increases frontal dopamine release via the 5-HT2a receptor, so might work although its track record isn't as good as buspirone's.

am worried about the withdrawals from brintellix when I cross taper to imipramine and really worried that it could all go horribly wrong and end up in hospital again.

Switching between SSRIs and TCAs isn't as easy as from one SSRI to another, and much of the data is from TCA to SSRI switches, but it usually goes relatively well. You also have the added benefit of mirtazapine, pregabalin and diazepam to dampen any anxiety swings. It will likely go much better than you fear. Getting into the right frame of mind is important as an anxious mind can create greater havoc than the meds if allowed free reign.

[SideFX]

Too much/little serotonin, probably not, at least not directly. It is more likely an indirect suppression of dopamine transmission by serotonin activity. The 5-HT1a receptor agonist buspirone (Buspar) is often prescribed for SSRI/SNRI induced bruxism. It is thought to work by enhancing dopamine transmission and increasing dopamine release in the frontal cortex. Buspirone may also alleviate other SSRI/SNRI side-effects such as sexual dysfunction and boost the effectiveness of these ADs. Unfortunately, you probably won't get it on the NHS. Seems they're not fans.



Mirtazapine also increases frontal dopamine release via the 5-HT2a receptor, so might work although its track record isn't as good as buspirone's.



Switching between SSRIs and TCAs isn't as easy as from one SSRI to another, and much of the data is from TCA to SSRI switches, but it usually goes relatively well. You also have the added benefit of mirtazapine, pregabalin and diazepam to dampen any anxiety swings. It will likely go much better than you fear. Getting into the right frame of mind is important as an anxious mind can create greater havoc than the meds if allowed free reign.

Thanks Ian

I have read that buspar can be a solution to SSRI induced bruxism...However that would mean me moving from Mirtazipine to buspar and that still doesn’t resolve my overall problem of not reaching remission...The Pdoc is talking of lowering the Mirtazipine, not increasing it and as you will know at higher doses it can become more activating.

I just feel this current combo of meds is causing me more problems, whilst helping me focus to work...However after over 2 years I would have expected to be fully recovered. Would you agree ???

And as I’m not fully recovered and still fell Anxiety, agitation and down then this poly pharmaceutical approach ain’t working. But I need to reach a stable point that I can start reducing Pregabalin and Diazipam for sure !!!!

I don’t want to be poly drugged and if you look at the *StarD study, level 4 was Venlafaxine plus Mirtazipine or an MAOI. Now as I’ve once recovered on the Ven/Mirt combo, but can no longer tolerate Ven or any SRI medication for some reason. It causes my skin to burn real bad and not in patches, but all over. And the docs wouldn’t believe me, which has been very frustrating I can tell you.

I even saw a dermatologist and he said it’s most probably a reaction to the SRI. I’m hoping so much that TCA’s don’t have the same reaction and when I tried amitriptyline very briefly this side effect wasn’t triggered. Plus TCA’s are used for nerve pain including burning and stabbing pain...This is why I’m gravitating to imipramine. Also mum did so well on it along with 3mg lorazepam.

I have also tried to research moving from an SSRI to a TCA and there is virtually nothing out there. However there’s lots of stuff on moving the other way...Seems strange as I would have thought after first line SSRI’s they would move to second line TCA’s and then to third line MAOI’s. Therefore studies around this progression would be readily available!!!!! Thanks again Ian

[panic_down_under]

I have read that buspar can be a solution to SSRI induced bruxism...However that would mean me moving from Mirtazipine to buspar and that still doesn’t resolve my overall problem of not reaching remission...

You can take buspirone with mirtazapine, assuming you can get it at all. It might even boost vortioxetine effectiveness, althought it is itself a weak serotonin 5-HT1a receptor partial agonist.

The Pdoc is talking of lowering the Mirtazipine, not increasing it and as you will know at higher doses it can become more activating.

It does become less sedating as the dose increases. I'm not sure you could call that more activating, although it can trigger strong paradoxical reactions in some.

I just feel this current combo of meds is causing me more problems, whilst helping me focus to work...However after over 2 years I would have expected to be fully recovered. Would you agree ???

If the combo was working well I would have expected better results within 4-6 months.

It causes my skin to burn real bad and not in patches, but all over. And the docs wouldn’t believe me, which has been very frustrating I can tell you.

Neuropathy and a host of other nerve and skin conditions are <> listed side-effects. Your doctors are clearly of the mushroom school of 'bedside manner', i.e. keep their patients in the dark and feed them male bovine manure...or ignorant!

If doctors were simply honest with their patients support groups would have much less traffic!

I have also tried to research moving from an SSRI to a TCA and there is virtually nothing out there. However there’s lots of stuff on moving the other way...

I take the view that if it works okay going one way it will likely work well in the reverse direction too.

[SideFX]

You can take buspirone with mirtazapine, assuming you can get it at all. It might even boost vortioxetine effectiveness, althought it is itself a weak serotonin 5-HT1a receptor partial agonist.



It does become less sedating as the dose increases. I'm not sure you could call that more activating, although it can trigger strong paradoxical reactions in some.



If the combo was working well I would have expected better results within 4-6 months.



Neuropathy and a host of other nerve and skin conditions are <> listed side-effects. Your doctors are clearly of the mushroom school of 'bedside manner', i.e. keep their patients in the dark and feed them male bovine manure...or ignorant!

If doctors were simply honest with their patients support groups would have much less traffic!



I take the view that if it works okay going one way it will likely work well in the reverse direction too.

Thanks for validating that Neuropathy and skin reactions are indeed med side effects and my only way of controlling that right now is by taking Pregabalin, which is for Neuropathy and pain. So without that I would have no way tolerated the Brintellix, which continues to cause it...I thought if I force my body to accept it it would resolve itself

However it is still a lingering side effect and doesn’t lift my depression fully, nor my anxiety. So I’m pressing on until a suitable time when I may feel in a position to take that leap of faith to imipramine.

My concern is that the Neuropathy becomes permanent and won’t fade once I switch to a TCA med...I’ve asked my GP the question and also the bruxism and she will not commit herself or even say there is a good chance (Talk about sitting on the fence) But the truth is they have no idea of what these meds do and I only wish every psychiatrist had to take a therapeutic dose of the meds they prescribe and then I would feel they are in a position to validate some of their claims.

One last ask please ian...When I was put on quetiapine I would get vibrations in my legs and body and feel disoriented upon waking...This has faded, but still plagues me after more than 2 years. Again I have spoke to my Pdoc, who is completely disinterested...I feel I did something to my dopamine receptors for sure...Any thoughts with your med knowledge ???? Thanks John