Why are SSRI’s too stimulating !!!!!!

[panic_down_under]

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.

[SideFX]

Surely your GP can't be in charge of prescribing all these drugs?

No Pulsa it’s my phychiatrist who prescribes and every day I go through a really bad patch, where I still struggle to function!!!! It’s shite pal and brings the dark thoughts back to the front of my mind... thank you John

[SideFX]

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

[panic_down_under]

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.

[AntsyVee]

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.

^^^Very true. I think it's like this for most drugs for about any condition. I know I've had to experiment with different kinds/combos for my allergy meds. I had to do it with birth control. My buddy had to do it with their asthma meds. Another friend had to do it with diabetes pumps vs. injection vs. pills. It's just the way it works. Just think, the sooner you get starter, the faster you're on your way to figuring it out.

[SideFX]

^^^Very true. I think it's like this for most drugs for about any condition. I know I've had to experiment with different kinds/combos for my allergy meds. I had to do it with birth control. My buddy had to do it with their asthma meds. Another friend had to do it with diabetes pumps vs. injection vs. pills. It's just the way it works. Just think, the sooner you get starter, the faster you're on your way to figuring it out.

Thanks PDU I’ve got a week or so to pitch my tent in one camp and as you say, until I try something different nothing is gonna change and I’m just gonna continue scrapping along, missing out on my life. Pandemic put to one side...I have said that if I got Covid and if finished me of, that would be fine by me and that’s just not normal.

I do get relief now in the evening and feel much more hopeful and stable, but never full remission and I’ve settled for not second but third or fourth best ie the best of the worst.

Do you think that the Pregabalin might be causing depression and anxiety, as it’s not a very nice drug and half life is an issue. I keep thinking yeah I’ve got it straight in my head, then think no I haven’t - I’m scared of the consequences of switching meds it really is a huge fear right now.

What do I do if it all goes south and I could lose everything I’ve pushed through and worked to put my life back together !!!!! It’s a truly scary thought and I imagine the worst case scenario I can’t help it pal. So it’s amatryptiline or come of pregabs????? Your thoughts on the pregab as it gives me many SideFX too thank you John

[panic_down_under]

I have said that if I got Covid and if finished me of, that would be fine by me and that’s just not normal.

No, it isn't. A permanent 'solution' to a temporary problem never is, John.

Do you think that the Pregabalin might be causing depression and anxiety, as it’s not a very nice drug and half life is an issue.

Not directly, but if it is causing problems then that can get people down.

What do I do if it all goes south and I could lose everything I’ve pushed through and worked to put my life back together !!!!!

This may not be an either/or decision, John. How long before your situation improves enough to be able to risk changing meds without losing everything should it go pear shaped and can you keep going the ways things are atm until then? You need to make your situation clear to your psychiatrist so that it is taken into consideration in formulating the plan of action.

So it’s amatryptiline or come of pregabs????? Your thoughts on the pregab as it gives me many SideFX too

If you came off pregabalin first where would that leave you? The entire combination of meds you're on aren't working that well and taking one out of the mix is unlikely to improve things, imo, but it could make things worse. Replacing the ineffective AD with one that may work with fewer side-effects is more likely to help.

[SideFX]

No, it isn't. A permanent 'solution' to a temporary problem never is, John.



Not directly, but if it is causing problems then that can get people down.



This may not be an either/or decision, John. How long before your situation improves enough to be able to risk changing meds without losing everything should it go pear shaped and can you keep going the ways things are atm until then? You need to make your situation clear to your psychiatrist so that it is taken into consideration in formulating the plan of action.



If you came off pregabalin first where would that leave you? The entire combination of meds you're on aren't working that well and taking one out of the mix is unlikely to improve things, imo, but it could make things worse. Replacing the ineffective AD with one that may work with fewer side-effects is more likely to help.

Sorry for the late response PDU thanks as usual for very wise words and I have thought that Pregabalin would stop me falling asleep - gaining weight - water in ears and head sensation....But could make other SideFX much worse.

It all scares the shit out of me right now and has done for years. I just don’t want to go the same way as my parents and feel that a bad decision could lead to that !!!! Like you say I will speak with my Pdoc who thinks reducing Mirtazipine is the way to go, but I don’t see the benefit - So I’ll throw the ball firmly in his court and see what he comes up with.

Thank you and I will post back after I see him on the 16th if that’s okay Ta John

[SideFX]

Sorry for the late response PDU thanks as usual for very wise words and I have thought that Pregabalin would stop me falling asleep - gaining weight - water in ears and head sensation....But could make other SideFX much worse.

It all scares the shit out of me right now and has done for years. I just don’t want to go the same way as my parents and feel that a bad decision could lead to that !!!! Like you say I will speak with my Pdoc who thinks reducing Mirtazipine is the way to go, but I don’t see the benefit - So I’ll throw the ball firmly in his court and see what he comes up with.

Thank you and I will post back after I see him on the 16th if that’s okay Ta John

BTW PDU What role does increasing Norepinephrine play in anxiety and panic disorder - Surely this would increase anxiety??? Ta John

[pulisa]

It's probably a stupid question but what does your psychiatrist say about referring you for trauma therapy? Meds don't appear to be doing much for you long term yet you have the legacy of what happened to your parents hanging over you and haunting you permanently..Medication change will add to that awful fear as you say..