Why are SSRI’s too stimulating !!!!!!

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You've been through so much trauma, SideFX and I can understand your need to medicate yourself through the ongoing pain of daily life.

I have a diagnosis of "agitated depression" from way back and like you found SSRIs just added to the problem. My son is on a whole cocktail of meds including vortioxetine and quetiapine after being sectioned last year. They don't really touch him, depression-wise, but have limited the self-harming.

One psychiatrist we consulted said that in her experience TCAs worked better in males than SSRIs/SNRIs. Trouble is, every psychiatrist has a different "favourite" med and you're at the mercy of their area of expertise. I find with my son it's a question of throwing the book at the problem and hoping something works..I've preferred the less is more approach for myself.

When you're under pressure to be functioning in your life it makes med choice all the more critical. Are you actually happy with your psychiatrist?

Hi pulsar, my first episode I was put on Peroxatine and that suited me until many stops and starts later it nearly killed me !!! As PDU says that’s the risk of stopping and restarting meds and boy did it do a demolition of my MH...I have a councillor, albeit private as NHS support is utter crap.

I have a really good relationship with my Pdoc and he really wants to help, but I don’t feel he really knows where to go med wise. The only thing he mentioned was reducing Mirtazipine, which I know is a waste of time doing....So he looks to me for the suggestions now and I thought Pregabalin could be causing me issues, however after chatting with PDU I’m thinking that I may be barking up the wrong tree !!! Thanks for your response and I’m sorry to hear about your son, can you not try a TCA for him ? Ta John

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I have a really good relationship with my Pdoc and he really wants to help, but I don’t feel he really knows where to go med wise.

Sigh!! He has one job...just one job, selecting meds.

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Sigh!! He has one job...just one job, selecting meds.

That’s exactly what I think he’s qualified and the professional in this relationship, so why turn to me for suggestions...As I’ve said he’s willing to go with my choice. But is that not a case of if things go south it wasn’t his decision and therefore not his responsibility!!!! Nice fella, but thinks that meds aren’t the answer well WTF and why did he train as a professional in psychiatric medication.

Makes me feel I’m alone to make my own choices, which is both good and bad !!!!

As I’ve recovered on serotegenic medication previously (Peroxatine and Effexor) I am leaning to imipramine. This was also the med my mum switched to, when they took her off the MAOI many years ago and she was great on it....So that’s why it attracts me so much PDU Ta John

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The most effective AD I've tried was the MAOI phenelzine (Nardil). Unfortunately, dietary issues were a problem back in the 1980s which became a real pain in the posterior, but these days much less so because modern food processing techniques create significantly less tyramine, plus we now know that adjunct doses of a NRI like desipramine and nortriptyline will pretty much block the response if a high tryramine dose food is eaten. However, should I need to go back onto a MAOI then it would be tranylcypromine (Parnate) as seems to provide a smoother 'ride' than the rocket fuel derive phenelzine.



Because I think it is less important than switching the AD, might still be having a positive effect on anxiety and it could speed up neurogenesis a little by accelerating the maturation of the new cells.



Imipramine is a fairly potent serotonin reuptake inhibitor, in fact slightly more so than vortioxetine, so there may be a small risk of triggering serotonin syndrome/toxicity when taking both. Nortriptyline is a much weaker SRI, so much so that before SNRIs were readily available it was quite common to prescribe it and a SSRI, usually sertraline, at highish doses to create a bespoke SNRI. Some old time psychiatrists still prefer the combo to a SNRI.



Understood, which is why I think it preferable to not leave you untreated while switching if possible as you would be when stopping the vortioxetine before starting a TCA, John.



Tsk, tsk. Never a good idea, mate, not even if someone like me suggests it. Your GP, or psychiatrist should always be the gatekeeper as they have both the expertise, and even more importantly, a better grasp of your mental and physical state and the meds you are and have taken.

Hi PDU I agree in that MAOI’s are the king of AD’s and it’s a shame they got such a bad wrap about the tyramine issue which as you say is much less so due to our modern food processing !

Thing is if it wasn’t for the bruxism, burning, hot flashes and shakiness vortioxatine is a good AD - But guess I’ve answered my own question, as these SideFX are not acceptable, albeit I have tried to force my body to accept them

It makes me feel like I’m playing snakes & ladders and have got over half way up the board and I’m about to roll the dice, which could have 3 outcomes (1) I land on a snake and slide all the way back down the board (2) I don’t land on a snake or ladder and (3) I land on a ladder, which moves me up the board !!!

The only reason I am where I am is down to tenacity and pushing regardless of how I feel and what role has vortioxatine played. Truth is I honestly don’t know and if anyone does, please share it with me....Thanks PDU

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Hi PDU I agree in that MAOI’s are the king of AD’s and it’s a shame they got such a bad wrap about the tyramine issue which as you say is much less so due to our modern food processing !

Thing is if it wasn’t for the bruxism, burning, hot flashes and shakiness vortioxatine is a good AD - But guess I’ve answered my own question, as these SideFX are not acceptable, albeit I have tried to force my body to accept them

It makes me feel like I’m playing snakes & ladders and have got over half way up the board and I’m about to roll the dice, which could have 3 outcomes (1) I land on a snake and slide all the way back down the board (2) I don’t land on a snake or ladder and (3) I land on a ladder, which moves me up the board !!!

The only reason I am where I am is down to tenacity and pushing regardless of how I feel and what role has vortioxatine played. Truth is I honestly don’t know and if anyone does, please share it with me....Thanks PDU

Can I resurrect this conversation as I’m due to see my Pdoc on the 16th and it’s gonna be a heavy conversation I know that

What I’m interested in understanding is the crossover from vortioxatine to imipramine...The NHS data I’ve looked at states “Reduce vortioxatine to 10mg and then carefully cross taper with a low dose TCA” - The process is only different if moving over to clomiprimine, as this is a very strong serotonin biased TCA and I would have to reduce vortioxatine to 10mg and stop, then start a very low dose of clomiprimine the very next day.

Can anyone validate my understanding above, so I am in an informed position to speak with him please ???? Ta John

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What I’m interested in understanding is the crossover from vortioxatine to imipramine...The NHS data I’ve looked at states “Reduce vortioxatine to 10mg and then carefully cross taper with a low dose TCA” - The process is only different if moving over to clomiprimine, as this is a very strong serotonin biased TCA and I would have to reduce vortioxatine to 10mg and stop, then start a very low dose of clomiprimine the very next day.

Sounds about right, John. Imipramine and vortioxetine have similar potency at inhibiting serotonin reuptake, 1.4 Ki and 1.6 Ki respectively, but clomipramine is much more potent at 0.14 Ki (and thus probably not for you anyway). The other factor is vortioxetine has a longish half-life, about 60 hr so it takes a couple of days to get plasma levels down. On the plus side you're unlikely to develop significant withdrawal symptoms. BTW-how much vortioxetine are you on, 20mg?

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Sounds about right, John. Imipramine and vortioxetine have similar potency at inhibiting serotonin reuptake, 1.4 Ki and 1.6 Ki respectively, but clomipramine is much more potent at 0.14 Ki (and thus probably not for you anyway). The other factor is vortioxetine has a longish half-life, about 60 hr so it takes a couple of days to get plasma levels down. On the plus side you're unlikely to develop significant withdrawal symptoms. BTW-how much vortioxetine are you on, 20mg?

Hi PDU nice to hear from you...Yeah the 60hr half life will play a part hopefully and smooth the crossover, albeit I’m expecting withdrawal symptoms from dropping vortioxatine as I’ve been taking it for 3 years and during the first 18 months I was on 10mg as I was scarred to raise it higher, this was due to what I am pretty sure is SideFX from it.

Anyway as I was struggling so badly after 18 months I said sod it I’ll jump to 20mg and it didn’t really make the SideFX any worse and over several months begin to bring me greater relief from my symptoms - But never brought me remission and the burning, along with agitation and anxiety were still present, although they had reduced.

Think ever since I had a complete melt down whilst trying to reinstate Peroxatine my response to AD’s changed and the 6 week kick in no longer applied...I don’t know what happened back then but my head exploded into a million pieces and I was a complete mess. I have had an MRI scan but that has showed nothing wrong and I have never had that response to meds since. Thing is at that time my head wouldn’t stabilise and I was a shaking wreck for a long time.

Anyway I’m thinking imipramine as it has a good SNRI effect, in that it’s ki figure is very close to vortioxatine, but Peroxatine is closer to Clomipramine in terms of ki it has a Sert ki of 0.34 and a Nert ki of 40 which matches Clomipramine ???? Have I got that right ? Because it was the best AD at first by a mile.

Whereas venlafaxine is around Sert ki 9 Nert ki 500ish and took a year or so to pull me free from depression and anxiety....So there’s a part of me drawn to Clomipramine, but I know imipramine suited mum, so that’s a big pull for me and the the change in mechanism of action I hope is more tolerable than SSRI’s as I have reacted badly to Venlafaxine, Duloxetine, Sertraline, Trazadone and vortioxatine....So I need some experience and reassurance from somebody who has experience of imipramine and I know you were once on it for some time....If you don’t mind me asking why did you switch and how did you do it and did you have any symptoms, either withdrawal or start up - Thanking you for your valued input and sorry this post is so long

So I’m currently on 20mg vortioxatine and would need to reduce to 10mg, assuming my Pdoc looks up the guidance and it matches what I’ve found from NHS England on the internet Ta John

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Anyway I’m thinking imipramine as it has a good SNRI effect, in that it’s ki figure is very close to vortioxatine, but Peroxatine is closer to Clomipramine in terms of ki it has a Sert ki of 0.34 and a Nert ki of 40 which matches Clomipramine ???? Have I got that right ? Because it was the best AD at first by a mile.

Despite the closeness of the raw Ki binding figures, clomipramine is a much more potent serotonin and noradrenaline/norepinephrine reuptake inhibitor than paroxetine. There is a greater difference between paroxetine's 0.34 Ki and clomipramine's 0.14 Ki than the numbers suggest.

Whereas venlafaxine is around Sert ki 9 Nert ki 500ish and took a year or so to pull me free from depression and anxiety....

Venlafaxine is SERT: 7.7 Ki and NET: 2753 Ki. Even 500 Ki is almost nothing, at 2753 Ki it has little effect on noradrenaline/norepinephrine reuptake even at the maximum 375mg dose. Despite what it says in the tin, it is only a SSRI, not SNRI, and not a particularly potent one. I don't understand its popularity in the UK in light of that and also the problems its short half-life cause.

So there’s a part of me drawn to Clomipramine, but I know imipramine suited mum, so that’s a big pull for me and the the change in mechanism of action I hope is more tolerable than SSRI’s as I have reacted badly to Venlafaxine, Duloxetine, Sertraline, Trazadone and vortioxatine....

Which is why I think you shouldn't be on a high potency SERT inhibitor, John. Imipramine would be as potent as I'd go, and there is a strong case for amitriptyline, imho.

What was the problem with trazodone? Didn't work, too sedating, or another side-effect?

So I need some experience and reassurance from somebody who has experience of imipramine and I know you were once on it for some time....If you don’t mind me asking why did you switch and how did you do it and did you have any symptoms, either withdrawal or start up

I was on imipramine for about 8 years, mostly at 300mg/day and 350mg for some months. Worked great, but at those doses alleviating the dry mouth and constipation was a daily battle so a new shrink suggested dosulepin/dothiepin/prothiaden which back then was thought to be safer than imipramine at high doses. Turns out it is actually the most cardio toxic AD by a long shot which is why it has been pulled from the BNP and prescribing to new patients is discouraged in the UK, though so far not here although recently the price has increased for some reason. Wonder if it's a hint. On a more positive note I have no apparent side-effects at even at 225mg which is above the recommended limit.

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Despite the closeness of the raw Ki binding figures, clomipramine is a much more potent serotonin and noradrenaline/norepinephrine reuptake inhibitor than paroxetine. There is a greater difference between paroxetine's 0.34 Ki and clomipramine's 0.14 Ki than the numbers suggest.



Venlafaxine is SERT: 7.7 Ki and NET: 2753 Ki. Even 500 Ki is almost nothing, at 2753 Ki it has little effect on noradrenaline/norepinephrine reuptake even at the maximum 375mg dose. Despite what it says in the tin, it is only a SSRI, not SNRI, and not a particularly potent one. I don't understand its popularity in the UK in light of that and also the problems its short half-life cause.



Which is why I think you shouldn't be on a high potency SERT inhibitor, John. Imipramine would be as potent as I'd go, and there is a strong case for amitriptyline, imho.

What was the problem with trazodone? Didn't work, too sedating, or another side-effect?



I was on imipramine for about 8 years, mostly at 300mg/day and 350mg for some months. Worked great, but at those doses alleviating the dry mouth and constipation was a daily battle so a new shrink suggested dosulepin/dothiepin/prothiaden which back then was thought to be safer than imipramine at high doses. Turns out it is actually the most cardio toxic AD by a long shot which is why it has been pulled from the BNP and prescribing to new patients is discouraged in the UK, though so far not here although recently the price has increased for some reason. Wonder if it's a hint. On a more positive note I have no apparent side-effects at even at 225mg which is above the recommended limit.

Hi PDU Trazadone was useless it made me fall asleep and wake up every hour and the anxiety was no better, hence depression continued...I did ask the Pdoc whilst I was in hospital at the time for imipramine, but he came back with Trazadone and it was of no use whatsoever....Are you thinking amitryp because it is fairly balanced ???? I did take it once and as I said before it just knocked me out. It’s a strong hitter on histamine so that’s no surprise.

I then left it for a few days and after taking my Mirtazipine along with Duloxetine I took amatryp cause I just wanted to be knocked out, which it did but I had massive, tachycardia could it have been the cocktail ??? That put me off it and spooked me

Other than that I had no SideFX, no burning no agitation no anxiety, just so sleepy and that is to be expected. I have thought that amatryp would be a lower risk based on the above and it’s sedative effects...I would take it at bedtime. But I’m not sure if it’s ability to tackle highly anxious highly agitated depression????? Your thoughts would be welcomed

Oh and amitriptyline would be easily available due to it and nortriptyline being used for fibro and neuropathic pain

I need to get this right this time no room for error, even though it’s a lottery it needs to be a very well informed decision and as I don’t have anyone to bounce the decision of, outside of my Pdoc I value your responses ???? Thanks John


BTW This is the table I’m using
https://en.m.wikipedia.org/wiki/Clomipramine

Under Pharmacology they have a table for most AD’s ta

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Hi PDU Trazadone was useless it made me fall asleep and wake up every hour and the anxiety was no better, hence depression continued...I did ask the Pdoc whilst I was in hospital at the time for imipramine, but he came back with Trazadone and it was of no use whatsoever....

Trazodone only begins to become an AD at 150mg plus and most need to take at least 300mg to begin getting a positive outcome. Ideally, it should be a controlled/extended release formulation such as Oleptro which are better at keeping plasma levels above the sedation threshold.

Are you thinking amitryp because it is fairly balanced ????

Mostly because it is less serotonergic.

I then left it for a few days and after taking my Mirtazipine along with Duloxetine I took amatryp cause I just wanted to be knocked out, which it did but I had massive, tachycardia could it have been the cocktail ??? That put me off it and spooked me

It most likely was the cocktail. Was that your idea, or a doctor's?

But I’m not sure if it’s ability to tackle highly anxious highly agitated depression????? Your thoughts would be welcomed

The only way to know is by trying it. It all comes down to how an AD meshes with individual biology. No AD is intrinsically better for a particular disorder than others, though clomipramine and fluvoxamine for the OCD spectrum, might be the exception.

I need to get this right this time no room for error, even though it’s a lottery it needs to be a very well informed decision

As per above, there is no way of knowing how an AD will work other than trying it, John. Sorry, but no amount of poring through med data will find you *the* AD. You might as well pick one out of a hat.