Why are SSRI’s too stimulating !!!!!!

[SideFX]

I have lost hope in ever being in remission again from anxiety and depression and feel lost in the blur of which is which....I have always found remission in medication- But this episode has lasted over 4 years and I’m poly drugged, so so unsure and scared to try to change anything. As it may result in total disaster any advice or help please !!!!

[panic_down_under]

I have lost hope in ever being in remission again from anxiety and depression and feel lost in the blur of which is which....I have always found remission in medication- But this episode has lasted over 4 years and I’m poly drugged, so so unsure and scared to try to change anything. As it may result in total disaster any advice or help please !!!!

What are you taking, at what dose and what were you on the last time you achieved remission?

[SideFX]

What are you taking, at what dose and what were you on the last time you achieved remission?

I’m screwed PDU we have spoken before if you recall ??? I haven’t been able to tolerate any SRI meds, be it SSRI/SNRI they just cause untold skin burning and hot flashes

I therefore take Lyrica to help dampen this side effect and I also take Diazipam, Mirtazipine and Brintellix (The latter causing the burning)

I have tolorated this for 3 years trying to force my body to accept this painful and distressing Side Effect. But it’s still there, albeit not as fierce.

Lyrica is an awful drug - weight gain, black outs, diarrhoea, nose drip and water sensation in ears and head.

Brintellix- anxiety, skin burning, bruxism - although a good antidepressant effect. But not good enough!!!!!

Mirtazipine- relaxed feeling, after 10 years tolorance has built to its sedative effects

Diazipam - think this attenuates the Lyrica and not much else...But skip it and holy crap

Can’t see a way out I want the weight gone the anxiety gone the bruxism gone the skin burning gone the black outs gone the diarrhoea gone the running nose gone and of course the residual depression gone....All just get up and fly away !!!!! Dreams for now, but will loose everything in time I’m sure of that

Thanks if anyone had stuck with this post Ta J

[panic_down_under]

I’m screwed PDU we have spoken before if you recall ??? I haven’t been able to tolerate any SRI meds, be it SSRI/SNRI they just cause untold skin burning and hot flashes

...Brintellix- anxiety, skin burning, bruxism - although a good antidepressant effect. But not good enough!!!!!

No point in taking a med that doesn't work as well as you need especially if it is causing side-effects so unpleasant that you need to take other meds to make life barely bearable. :sad:


Lyrica is an awful drug - weight gain, black outs, diarrhoea, nose drip and water sensation in ears and head.

And you're taking this just to tolerate the vortioxetine induced burning sensation? :ohmy:

Btw - I suspect much of the weight gain is caused by the mirtazapine, not pregabalin.


Mirtazipine- relaxed feeling, after 10 years tolorance has built to its sedative effects

Sedation is about all mirtazapine does...and stack on weight.


Diazipam - think this attenuates the Lyrica and not much else...But skip it and holy crap

Yes, and it is counteracting the positive brain effects of the vortioxetine, although pregabalin might be lessening this to some extent.


Can’t see a way out I want the weight gone the anxiety gone the bruxism gone the skin burning gone the black outs gone the diarrhoea gone the running nose gone and of course the residual depression gone...

SSRIs and SNRIs are not the only ADs, or the most effective. The only advantage they have is being safer in overdose and this isn't actually true of all of them. You would likely to do much better with one of the TCAs and without all the other crap although you'll need to keep taking them for a while till you can slowly wean off them.

Who is your GP, the Marquis de Sade? :scared15: :curse: :mad:

[SideFX]

No point in taking a med that doesn't work as well as you need especially if it is causing side-effects so unpleasant that you need to take other meds to make life barely bearable. :sad:



And you're taking this just to tolerate the vortioxetine induced burning sensation? :ohmy:

Btw - I suspect much of the weight gain is caused by the mirtazapine, not pregabalin.



Sedation is about all mirtazapine does...and stack on weight.



Yes, and it is counteracting the positive brain effects of the vortioxetine, although pregabalin might be lessening this to some extent.



SSRIs and SNRIs are not the only ADs, or the most effective. The only advantage they have is being safer in overdose and this isn't actually true of all of them. You would likely to do much better with one of the TCAs and without all the other crap although you'll need to keep taking them for a while till you can slowly wean off them.

Who is your GP, the Marquis de Sade? :scared15: :curse: :mad:

Thanks PDU I have a good understanding of TCA’s and even MOAI’s, but the thought of going through all the trial and error with AD’s again will be the end of me.

However I can’t live a full quality of life as is and in the past I found Peroxatine to be my saviour. It was beautiful and I was a poster child for it....But I came off and went back on it to many times, then it bit my arse big time. I thought nothing would ever help again....Then I researched and asked for Effexor, which didn’t cause any SideFX and eventually worked up to 375mg and still no relief.

They tried adding meds but I couldn’t tolerate them, until Mirtazipine came along and I slept like a baby and felt my crushing depression beginning to lift, albeit a very slow process. Which only ended up in full remission after nearly a year and then titrated off the diazipam.

But now I can’t tolerate any SRI meds, they all cause the same side effects hot burning stinging sensation...I have kicked around switching to imipramine, but I don’t have the bottle to risk it !!!!!

I know you were once on imipramine and it worked very well for my mum too. I’ve got a job and house that would be at risk if it goes pear shaped.

So feel trapped in this situation of my own making !!!

[panic_down_under]

But now I can’t tolerate any SRI meds, they all cause the same side effects hot burning stinging sensation...I have kicked around switching to imipramine, but I don’t have the bottle to risk it !!!!!

You don't necessarily need to jump from the frying pan into the fire. Talk to your GP about doing a slow cross taper. I suggest switching to amitriptyline rather than imipramine as it is less serotonergic so eliminating the risk of simulating the burning sensation by synergy.

The norepinephrine reuptake inhibitor nortriptyline is another possibility. In the past it was often prescribed with sertraline, both at highish doses, to make a bespoke SNRI. Vortioxetine+nortriptyline is likely to be more effective combo than vortioxetine+mirtazapine and you could slowly reduce the vortioxetine to a dose you can tolerate, or wean off it completely.

[AntsyVee]

Hang in there buddy, you’ll get it figured out eventually

[SideFX]

You don't necessarily need to jump from the frying pan into the fire. Talk to your GP about doing a slow cross taper. I suggest switching to amitriptyline rather than imipramine as it is less serotonergic so eliminating the risk of simulating the burning sensation by synergy.

The norepinephrine reuptake inhibitor nortriptyline is another possibility. In the past it was often prescribed with sertraline, both at highish doses, to make a bespoke SNRI. Vortioxetine+nortriptyline is likely to be more effective combo than vortioxetine+mirtazapine and you could slowly reduce the vortioxetine to a dose you can tolerate, or wean off it completely.

Hi PDU I appreciate your input and suggestions...I feel the only way forward reality is to start by swapping out the Vortioxatine, as I feel this is causing the most distressing side effects. Ie. Skin burning, bruxism and it’s useless for anxiety.

And as I consider myself to suffer from highly anxious and agitated depression, so anything that may stimulate will make matters worse not better, or even remain the same.

I have a full awareness of Dr Ken Gillman and his YouTube channel, plus website and it all sounds accurate good information to me.

However why did I completely recover after only 6 weeks on Peroxatine??? It was an amazing AD and is the strongest SSRI. I have never had a drug turn me round so fast and make me feel so good...Why is that ???? I don’t know !!!!

If I could only find another Peroxatine I would be a happy man again, for now I live a life, albeit not to the quality I used to have.

Truth is I’m on 4 meds and they don’t play nice together, so I have been trying to work out what’s causing what and think I’ve got a handle on that.

I understand the difference between TCA’s some being bias toward serotonin and some bias to noradrenaline and some more balanced ie. Amitriptyline and some bias to noradrenaline ie. Nortriptyline....But to be honest I don’t think it’s the serotonin that’s the problem, I think it’s the mechanism of action that’s causing it.

I took Amatriptyline a couple of times at the beginning of this protracted episode and first time just wanted to fall asleep, no other side effect, but the second time I took it I also took duloxetine and Mirtazipine and had a huge panic attack - I had to take a lot of Diazipam to stop it and that spooked me with it...Don’t know why this didn’t happen the first time.

As for weight gain PDU I agree Mirtazipine will make you sleep and eat - Well pregabalin will do the same so double the weight gain and your screwed !!!!

Also pregabalin isn’t a walk away from med and will blow up in doctors faces as Benzos did !!!! Their being dished out for everything!!!!

Sorry for rambling on so long - But I do feel TCA is the way to go, but not with vortioxatine, so swapping that out, without falling into the pit of debilitating depression and anxiety. I like the idea of Amatrip but that PA spooked me, I also like the idea of imip or even Clomipramine the strongest serotonin biased TCA.

I don’t have the burning reaction to TCA’s but it’s getting through the drop in one med and the start up of another and as you know people with high anxiety disorders don’t do well on switching meds !!!!

Thank you PDU your input is validating and adding value to my current knowledge, which is pretty good. But not as extensive as yours pal Ta John

[SideFX]

Hang in there buddy, you’ll get it figured out eventually

Thanks I’ve been battling for nearly 4 years now, which is too long and I never thought I’d still be trying to sort meds out for this long Ta John

[pulisa]

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

[AntsyVee]

Thanks I’ve been battling for nearly 4 years now, which is too long and I never thought I’d still be trying to sort meds out for this long Ta John

It took me 20 years to get mine sorted...but it's worth it.

[panic_down_under]

I have a full awareness of Dr Ken Gillman and his YouTube channel, plus website and it all sounds accurate good information to me.

I didn't know Ken had a YT channel. Thanks for the heads-up, John.


However why did I completely recover after only 6 weeks on Peroxatine??? It was an amazing AD and is the strongest SSRI. I have never had a drug turn me round so fast and make me feel so good...Why is that ???? I don’t know !!!!

Six weeks is when ADs are most likely to kick-in, at least for the first exposure. It tends to take progressively longer through each subsequent discontinuation/restart cycle. The side-effects also often gradually become more severe each time too, and they can be different at each time too. I don't think anyone knows why. Paroxetine isn't the most potent SSRI. Vortioxetine has a stronger affinity to serotonin transporters, as do escitalopram, sertralineand vilazodone and the SNRI duloxetine and the TCA clomipramine.


If I could only find another Peroxatine I would be a happy man again, for now I live a life, albeit not to the quality I used to have.

Parotetine has no intrinsic advantage. There is a good chance another AD will be just as effective, if not more so. But it can take a while to find it.


But to be honest I don’t think it’s the serotonin that’s the problem, I think it’s the mechanism of action that’s causing it.

It is being mediated through serotonin pathways. Serotonin has many roles in the body besides brain neurotransmission and the skin and its blood vessels utilize about as much serotonin as the brain does, a little less than 2% of the body's output.


I took Amatriptyline a couple of times at the beginning of this protracted episode and first time just wanted to fall asleep, no other side effect, but the second time I took it I also took duloxetine and Mirtazipine and had a huge panic attack - I had to take a lot of Diazipam to stop it and that spooked me with it...Don’t know why this didn’t happen the first time.

It can take a few days, sometimes weeks for the effects of an AD to cross the side-effects threshold. Amitriptyline is also a fairly potent antihistamine hence the sedation. Why someone would prescribe both it and duloxetine is puzzling unless it was part of a switch attempt.


Also pregabalin isn’t a walk away from med and will blow up in doctors faces as Benzos did !!!! Their being dished out for everything!!!!

Not a fan. Apart from the dependency and tolerance issues, almost everyone taking it ends up on at least one other med, often mirtazapine.


But I do feel TCA is the way to go, but not with vortioxatine, so swapping that out, without falling into the pit of debilitating depression and anxiety. I like the idea of Amatrip but that PA spooked me, I also like the idea of imip or even Clomipramine the strongest serotonin biased TCA.

If you wean off vortioxetine first then I think imipramine would be the better option of the three TCAs.


I don’t have the burning reaction to TCA’s but it’s getting through the drop in one med and the start up of another and as you know people with high anxiety disorders don’t do well on switching meds !!!!

It helps if there is a competent doctor supervising it and that is my reservation in your case, John. :ohmy: It was the second reason I suggested switching to nortriptyline rather than imipramine. Much harder to stuff it up.

[SideFX]

It took me 20 years to get mine sorted...but it's worth it.

Wow how did you cope and what saved you after 20 years...I’ve had a lot of good years on AD’s, but can’t get there now !!! Thanks John

[SideFX]

I didn't know Ken had a YT channel. Thanks for the heads-up, John.



Six weeks is when ADs are most likely to kick-in, at least for the first exposure. It tends to take progressively longer through each subsequent discontinuation/restart cycle. The side-effects also often gradually become more severe each time too, and they can be different at each time too. I don't think anyone knows why. Paroxetine isn't the most potent SSRI. Vortioxetine has a stronger affinity to serotonin transporters, as do escitalopram, sertralineand vilazodone and the SNRI duloxetine and the TCA clomipramine.



Parotetine has no intrinsic advantage. There is a good chance another AD will be just as effective, if not more so. But it can take a while to find it.



It is being mediated through serotonin pathways. Serotonin has many roles in the body besides brain neurotransmission and the skin and its blood vessels utilize about as much serotonin as the brain does, a little less than 2% of the body's output.



It can take a few days, sometimes weeks for the effects of an AD to cross the side-effects threshold. Amitriptyline is also a fairly potent antihistamine hence the sedation. Why someone would prescribe both it and duloxetine is puzzling unless it was part of a switch attempt.



Not a fan. Apart from the dependency and tolerance issues, almost everyone taking it ends up on at least one other med, often mirtazapine.



If you wean off vortioxetine first then I think imipramine would be the better option of the three TCAs.



It helps if there is a competent doctor supervising it and that is my reservation in your case, John. :ohmy: It was the second reason I suggested switching to nortriptyline rather than imipramine. Much harder to stuff it up.

Thanks again PDU, thing is I feel I’ve hit the tolerance wall with Pregabalin, as I wake feeling very down until it gets back into my body. This can take up to 2 and a half hours to peak. Then I’m more stable....It’s got a silly 6.5Hrs half life so gone in 12 hours !!!!

I have deliberated coming off Pregabalin, but am I just tearing off the fire blanket and screwed cause vortioxatine and it’s side effects could come back with avengamce !!!!

I need to either try dropping the pregab or swapping out the vortioxatine for a TCA. Therefore giving a different mechanism of action.

It’s a decision I’m finding very hard to make and could Pregabalin be causing my daily yo yo effect ?????

If you were in my position what would you go for and what would justify that decision....Please bear in mind that I have to work and maintain functionality. I can’t risk losing my home and job again - it would be the end of me.

Your thoughts please based on the above ??? Again a huge mega thanks John

[AntsyVee]

Wow how did you cope and what saved you after 20 years...I’ve had a lot of good years on AD’s, but can’t get there now !!! Thanks John

I did the best I could, but I had a lot of ups and downs. i've had GAD and depression since I was a little kid. I remember symptoms of anxiety as early as age 5, but when I was a kid, my parents didn't really know and/or understand what I was dealing with, and my bio mom had her own mental illness she never dealt with (I believe mine are genetic). The meds I was on as a kid never really did much for me except make the problems worse. When I became an adult, I tried a different few, but nothing did the trick. Therapy helped me immensely. I had gone off meds for several years between 2008 and 2014. But then in the fall of 2014, I lost my best friend, and my anxiety skyrocketed to the worst I've ever had it (I found his body). I got myself back into therapy, specifically grief counseling. I learned that I had C-PTSD as I didn't properly deal with other things that had happened to me before then, and my doctor said, "Hey, there is this new SSRI that they didn't have back in 2008 when you were last on meds, why don't you give it a try?" And I did. Lexapro. I take 20 mg daily and I love it. It's improved my quality of life so much. I'm so glad I've been on it for this pandemic because I'm not sure I'd be able to deal with the stress of everything that's happened without it.

[panic_down_under]

I wake feeling very down until it gets back into my body. This can take up to 2 and a half hours to peak. Then I’m more stable....It’s got a silly 6.5Hrs half life so gone in 12 hours !!!!

Are you taking pregabalin in an immediate-release or controlled/extended/slow-release formulation, John? Peak plasma levels are usually reached within 30-90 minutes of taking the immediate-release, 8-10 hours for the controlled-release.


It’s a decision I’m finding very hard to make and could Pregabalin be causing my daily yo yo effect ?????

Yes, it could. But it could just be your mood is usually lower in the mornings. We split about 50:50 in being most affected by these disorders either in the mornings, or late in the day.


If you were in my position what would you go for and what would justify that decision....Please bear in mind that I have to work and maintain functionality. I can’t risk losing my home and job again - it would be the end of me.

Given your circumstances, I'd go for a slow cross taper from vortioxetine to a TCA, either amitriptyline, or its main metabolite nortriptyline as you'd still be treated throughout the switch and it would usually be easier/quicker to recover if things go amiss. Quitting vortioxetine and then starting the TCA will leave you exposed for some weeks. But the final arbiter on this will be your doctor/s. I suspect they'll opt for stopping the vortioxetine before prescribing a TCA. You might even get resistance to TCAs. Many doctors have little experience of them and believe, wrongly (https://www.psychiatrictimes.com/view/not-obsolete-continuing-roles-tcas-and-maois), that they are inferior to SSRIs/SNRIs when the opposite is the case.

[SideFX]

I did the best I could, but I had a lot of ups and downs. i've had GAD and depression since I was a little kid. I remember symptoms of anxiety as early as age 5, but when I was a kid, my parents didn't really know and/or understand what I was dealing with, and my bio mom had her own mental illness she never dealt with (I believe mine are genetic). The meds I was on as a kid never really did much for me except make the problems worse. When I became an adult, I tried a different few, but nothing did the trick. Therapy helped me immensely. I had gone off meds for several years between 2008 and 2014. But then in the fall of 2014, I lost my best friend, and my anxiety skyrocketed to the worst I've ever had it (I found his body). I got myself back into therapy, specifically grief counseling. I learned that I had C-PTSD as I didn't properly deal with other things that had happened to me before then, and my doctor said, "Hey, there is this new SSRI that they didn't have back in 2008 when you were last on meds, why don't you give it a try?" And I did. Lexapro. I take 20 mg daily and I love it. It's improved my quality of life so much. I'm so glad I've been on it for this pandemic because I'm not sure I'd be able to deal with the stress of everything that's happened without it.

I’m sorry to hear your decades of enduring depression and anxiety and your genetic history...I unfortunately saw my mum try to take her life when I was about 13, she took nearly 200 paracetamol and how she survived is a miracle. My dad took his life in 93 and I was the unfortunate to find him !!!! That was a tough time, but it was just a case of get on with it in those days

I had my first nervous breakdown in 2001 in my 30’s and it happened so quickly within weeks I was ready to end it all. Then I was prescribed Peroxatine and Yipeeee I felt on top of the world...Many stops and starts on meds left me in the deepest black hole ever and it was Effexor & Mirtazipine that eventually pulled me out of it, but as usual I stop taking meds and I get burnt again. This time I am struggling to get there and can’t see why I want to at times thanks for sharing your history it’s not easy Ta John

[SideFX]

Are you taking pregabalin in an immediate-release or controlled/extended/slow-release formulation, John? Peak plasma levels are usually reached within 30-90 minutes of taking the immediate-release, 8-10 hours for the controlled-release.



Yes, it could. But it could just be your mood is usually lower in the mornings. We split about 50:50 in being most affected by these disorders either in the mornings, or late in the day.



Given your circumstances, I'd go for a slow cross taper from vortioxetine to a TCA, either amitriptyline, or its main metabolite nortriptyline as you'd still be treated throughout the switch and it would usually be easier/quicker to recover if things go amiss. Quitting vortioxetine and then starting the TCA will leave you exposed for some weeks. But the final arbiter on this will be your doctor/s. I suspect they'll opt for stopping the vortioxetine before prescribing a TCA. You might even get resistance to TCAs. Many doctors have little experience of them and believe, wrongly (https://www.psychiatrictimes.com/view/not-obsolete-continuing-roles-tcas-and-maois), that they are inferior to SSRIs/SNRIs when the opposite is the case.

Hi PDU thanks again and your valued input...Your correct I am treated by a Pdoc not a GP and he’s happy to move to a TCA and I’ve even dropped the MAOI bomb if TCA’s don’t work and he didn’t say no !!!!

I take instant release Pregabalin and it’s gone in 12 hours and working on the 5 half lives theory that’s 30 hours after a single dose (Not good) So you wouldn’t touch Pregabalin for now then ???? Why is that ????

Also why is nortriptyline a less risky option than imipramine??? Surely any switch is fraught with its own risks and I can’t afford to mess this up. I’ve pushed myself and worked so so so hard to rebuild my life, I could lose all that ground and couldn’t live with that.

If you look at my response to AntsyVee my past has not been a smooth one with suicide and mental health being a huge part of my life !!!!

As ever your input and continued support, through this decision making is very much appreciated Ta John

Oh and the duloxetine with amitriptyline was my doing not a doctors (Mistake I know) !!!!!

[pulisa]

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?

[panic_down_under]

I am treated by a Pdoc not a GP and he’s happy to move to a TCA and I’ve even dropped the MAOI bomb if TCA’s don’t work and he didn’t say no !!!!

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.


So you wouldn’t touch Pregabalin for now then ????

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.


Also why is nortriptyline a less risky option than imipramine??? Surely any switch is fraught with its own risks and I can’t afford to mess this up. I’ve pushed myself and worked so so so hard to rebuild my life, I could lose all that ground and couldn’t live with that.

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.


If you look at my response to AntsyVee my past has not been a smooth one with suicide and mental health being a huge part of my life !!!!

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.


Oh and the duloxetine with amitriptyline was my doing not a doctors (Mistake I know) !!!!!

Tsk, tsk. :nonono: 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.

[AntsyVee]

it was just a case of get on with it in those days

I stop taking meds and I get burnt again. This time I am struggling to get there and can’t see why I want to at times thanks for sharing your history it’s not easy Ta John

Hey John, I'm sorry to hear about your losses as well. I think one thing we have to accept is our genetic history and the fact that it makes us much more predisposed to problems. It is not something to take lightly. The "get on with it" attitude that people had towards me and the one that I had adopted (because I thought that was right at the time) almost did me in. So many things piled up for me because I didn't deal with them at the time.

You are going to be much more predisposed to suicide because of what happened with your parents. I think maybe you should consider staying on medication once you find the right combo/dosage that works for you. There is nothing that says that we need to come off the meds. It's fine to be on them for the rest of our lives.

TC,
Vee

[pulisa]

It's so important to find the right psychiatrist/psychologist too but that can be incredibly difficult with NHS MH services and private MH services are so expensive especially when needed on a long term basis.

[SideFX]

Hey John, I'm sorry to hear about your losses as well. I think one thing we have to accept is our genetic history and the fact that it makes us much more predisposed to problems. It is not something to take lightly. The "get on with it" attitude that people had towards me and the one that I had adopted (because I thought that was right at the time) almost did me in. So many things piled up for me because I didn't deal with them at the time.

You are going to be much more predisposed to suicide because of what happened with your parents. I think maybe you should consider staying on medication once you find the right combo/dosage that works for you. There is nothing that says that we need to come off the meds. It's fine to be on them for the rest of our lives.

TC,
Vee

Thanks I totally agree with everything you are saying and I said to myself last time (Never again) but thing is I get tired of the sexual side effects and I feel good, so think it’s time to come off...I was so stable last time that I could come off a large dose of Diazipam and reduce my Effexor to a more sensible level. Thanks for your concern and kindness Ta John

[SideFX]

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

[panic_down_under]

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 :curse: meds. :ohmy:

[SideFX]

Sigh!! He has one job...just one job, selecting :curse: meds. :ohmy:

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

[SideFX]

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. :nonono: 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

[SideFX]

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

[panic_down_under]

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?

[SideFX]

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

[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, :sad: but no amount of poring through med data will find you *the* AD. You might as well pick one out of a hat. :unsure:

[AntsyVee]

As per above, there is no way of knowing how an AD will work other than trying it, John. Sorry, :sad: 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..

[panic_down_under]

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.

Pregabalin has a similar effect on the brain as BZDs, just by a different route, John. BZDs slow neuron 'firing' by helping to increase the influx of negatively charged chlorine ions which makes it harder for the cell to raise its typical resting voltage from -70 mv to the depolarisation (firing) voltage of -55 mV, pregabalin inhibits the influx of positively charged calcium ions instead. Sedation is a common side-effect.


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

It might if noradrenaline/norepinephrine (NA) reuptake inhibitors increased NA levels - and they do for a few weeks at the beginning, but just as with serotonergic ADs and serotonin levels, with chronic dosing they actually reduce NA synthesis and expression. OTOH, anxiety and/or depression increase NA and serotonin (also dopamine) levels significantly. These disorders are not caused by too little of this, or that neurotransmitter, just the opposite. See: Zangen A (http://www.sciencedirect.com/science/article/pii/S0006899399012147), 1999 and my Serotonin - The 'chemical imbalance' myth (https://www.nomorepanic.co.uk/showthread.php?193671-Serotonin-The-chemical-imbalance-myth).

[SideFX]

Pregabalin has a similar effect on the brain as BZDs, just by a different route, John. BZDs slow neuron 'firing' by helping to increase the influx of negatively charged chlorine ions which makes it harder for the cell to raise its typical resting voltage from -70 mv to the depolarisation (firing) voltage of -55 mV, pregabalin inhibits the influx of positively charged calcium ions instead. Sedation is a common side-effect.



It might if noradrenaline/norepinephrine (NA) reuptake inhibitors increased NA levels - and they do for a few weeks at the beginning, but just as with serotonergic ADs and serotonin levels, with chronic dosing they actually reduce NA synthesis and expression. OTOH, anxiety and/or depression increase NA and serotonin (also dopamine) levels significantly. These disorders are not caused by too little of this, or that neurotransmitter, just the opposite. See: Zangen A (http://www.sciencedirect.com/science/article/pii/S0006899399012147), 1999 and my Serotonin - The 'chemical imbalance' myth (https://www.nomorepanic.co.uk/showthread.php?193671-Serotonin-The-chemical-imbalance-myth).

That was a very interesting link PDU...So all meds raise one or more level of neurotransmitters and then downstream this encourages neurogenesis, which in turn creates healthy normal levels of neurones....Thus recovery will be reached irrespective of the med, as long as it’s well tolerated ???? That makes sense to the delayed response Ta John

[panic_down_under]

So all meds raise one or more level of neurotransmitters

Yes, usually beginning within about an hour of the first dose, however, after a week or two bio-feedback mechanisms come into play and reduce synthesis and expression which causes the affected neurotransmitter levels to drop dramatically in some regions of the brain associated with anxiety/depression.


and then downstream this encourages neurogenesis, which in turn creates healthy normal levels of neurones....

Not sure if the drop in neurotransmitter levels is the important factor, but it is certainly seems to be part of the process.


Thus recovery will be reached irrespective of the med, as long as it’s well tolerated ????

No AD is intrinsically better than the others, however, one or two will often prove more effective than the others for an individual. Some also respond better to noradrenaline/norepinephrine reuptake inhibitors (NRI) such as nortriptyline, desipramine and lofepramine than they do serotonin reuptake inhibitors. Unfortunately, these days many GPs and even some psychiatrists are barely aware they exist. :sad: Old time psychiatrists also favour supplementing a SSRI with a NRI over prescribing SNRIs. Not only can they essentially create a bespoke SNRI, but it avoids some of the SNRIs problems such as their short half-lives which can make both starting and stopping them difficult.

[SideFX]

Yes, usually beginning within about an hour of the first dose, however, after a week or two bio-feedback mechanisms come into play and reduce synthesis and expression which causes the affected neurotransmitter levels to drop dramatically in some regions of the brain associated with anxiety/depression.



Not sure if the drop in neurotransmitter levels is the important factor, but it is certainly seems to be part of the process.



No AD is intrinsically better than the others, however, one or two will often prove more effective than the others for an individual. Some also respond better to noradrenaline/norepinephrine reuptake inhibitors (NRI) such as nortriptyline, desipramine and lofepramine than they do serotonin reuptake inhibitors. Unfortunately, these days many GPs and even some psychiatrists are barely aware they exist. :sad: Old time psychiatrists also favour supplementing a SSRI with a NRI over prescribing SNRIs. Not only can they essentially create a bespoke SNRI, but it avoids some of the SNRIs problems such as their short half-lives which can make both starting and stopping them difficult.

Okay PDU think I understand the way recovery is reached, or at least the mechanism involved in AD’s

So how come Peroxatine was a silver bullet and turned me around in circa 6 weeks - Yet the Mirtazipine & Venlafaxine combo took about a year ??? If the same mechanism is being triggered, why so long for the latter...The latter got me so stable I came of Diazipam easily and reduced Venlafaxine from 375 to 150 walk in the park.

I just can’t see any med doing what Peroxatine did ie kick in fully at 6 weeeks and it would be nice to know why the mechanism of TCA action is so different to SSRI’s which some people cannot tolerate...Am I also right in thinking that Peroxatine has an effect on NET as well as SERT and with a NET ki of circa 50 ???? Cause that balance was perfect for me, but I kept stopping and starting and it bit my arse big big time on the 3rd attempt to restart !!!!! Ta John

[panic_down_under]

So how come Peroxatine was a silver bullet and turned me around in circa 6 weeks - Yet the Mirtazipine & Venlafaxine combo took about a year ???

Maybe the improvement was due to remission, not the venlafaxine, John. Anxiety disorders and depression wax and wane over time. If an AD at maximum dose isn't working within 12 weeks or so, maybe an extra couple of weeks if it isn't the first time on ADs, or is fluoxetine, then it is unlikely to at 6/9/12 months.

Why did you keep taking mirtazapine and venlafaxine for so long if it wasn't working?


I just can’t see any med doing what Peroxatine did ie kick in fully at 6 weeeks

ADs usually kick-in at 4-12 weeks the first time with the top of the bell curve at 6 weeks.


and it would be nice to know why the mechanism of TCA action is so different to SSRI’s which some people cannot tolerate...

The dual action of most of them, plus the combination of receptors they hit.


Am I also right in thinking that Peroxatine has an effect on NET as well as SERT and with a NET ki of circa 50 ????

It is a more potent NET inhibitor than the other SSRIs but much less so that many of the TCAs.


Cause that balance was perfect for me, but I kept stopping and starting and it bit my arse big big time on the 3rd attempt to restart !!!!!

You might have done just as well on another SSRI.

[SideFX]

Hi PDU I know it’s been a long time and I would like to seek your advise again…In the end I remained on all 4 meds and over the past few years, got back to about 60/70% ability to cope with life.

However I have very slowly been tapering off the Pregabalin and got from 600mg to 150mg. Then I got slammed with huge withdrawals, or at least I am putting it down to the cumulative drop.

Anyway it’s been 5 weeks and although I feel a bit better, I’m still in distress and trying to continue working. Thing is I have the shakes, hot flashes, burning skin sensations back. Panic and anxiety, mixed with some depression. I fear the end is coming and I’m afraid and don’t know what to do. Could you kindly revisit this thread and give some valuable input, as I was never in remission after 6 long years. But able to get by, without everything being a white knuckle ride.

I am still on Vortioxitine, Mirtazapine, Diazepam and now up dosed to 300mg Pregabalin

My GP doesn’t know what to do and has advised that it could take some time to stabilise back to where I was 5 weeks ago. Not healed, but able to cope with life.

Can we have a discussion around meds please as I know you are a fountain of knowledge. Thanking you in advance John

[SideFX]

Maybe the improvement was due to remission, not the venlafaxine, John. Anxiety disorders and depression wax and wane over time. If an AD at maximum dose isn't working within 12 weeks or so, maybe an extra couple of weeks if it isn't the first time on ADs, or is fluoxetine, then it is unlikely to at 6/9/12 months.

Why did you keep taking mirtazapine and venlafaxine for so long if it wasn't working?



ADs usually kick-in at 4-12 weeks the first time with the top of the bell curve at 6 weeks.



The dual action of most of them, plus the combination of receptors they hit.



It is a more potent NET inhibitor than the other SSRIs but much less so that many of the TCAs.



You might have done just as well on another SSRI.

Hi PDU I know it’s been a long time and I would like to seek your advise again…In the end I remained on all 4 meds and over the past few years, got back to about 60/70% ability to cope with life.

However I have very slowly been tapering off the Pregabalin and got from 600mg to 150mg. Then I got slammed with huge withdrawals, or at least I am putting it down to the cumulative drop.

Anyway it’s been 5 weeks and although I feel a bit better, I’m still in distress and trying to continue working. Thing is I have the shakes, hot flashes, burning skin sensations back. Panic and anxiety, mixed with some depression. I fear the end is coming and I’m afraid and don’t know what to do. Could you kindly revisit this thread and give some valuable input, as I was never in remission after 6 long years. But able to get by, without everything being a white knuckle ride.

I am still on Vortioxitine, Mirtazapine, Diazepam and now up dosed to 300mg Pregabalin

My GP doesn’t know what to do and has advised that it could take some time to stabilise back to where I was 5 weeks ago. Not healed, but able to cope with life.

Can we have a discussion around meds please as I know you are a fountain of knowledge. Thanking you in advance John

[panic_down_under]

However I have very slowly been tapering off the Pregabalin and got from 600mg to 150mg. Then I got slammed with huge withdrawals, or at least I am putting it down to the cumulative drop.

...Thing is I have the shakes, hot flashes, burning skin sensations back. Panic and anxiety, mixed with some depression.

How long after the last dose decrease did you begin having these symptoms, John?


I am still on Vortioxitine, Mirtazapine, Diazepam and now up dosed to 300mg Pregabalin

My GP doesn't know what to do

Did he start you on all these meds, or a psychiatrist?

Imo, there are two significant issues with your med regime. Firstly there's now good evidence1 that benzodiazepines both worsen anxiety in the longer run and reduce the effectiveness of serotonergic ADs. The second is that the diazepam and pregabalin are basically doling the same job, slow the 'firing' rate of neurons, albeit from different directions. Diazepam does it by increasing the inflow of negatively charged chlorine ions which makes it harder for a cell to raise its electrical voltage to the depolarization level. Pregabalin slows firing by decreasing the influx of positively charged calcium ions. I don't see the point of taking two meds to do the same thing. It would have been more efficient to just raise the dose of one of them.

Which brings us to the other two. Despite what is says on the packaging, mirtazapine isn't a true AD, but a sedative so its main role in your case may be to help you sleep and it may reduce anxiety to some extent through sedation.

Vortioxetine combines the actions of a SSRI with that of buspirone (Buspar). It was noticed that buspirone can enhance the effectiveness of SSRIs and other serotonergic ADs and also ease some of their side-effects. So some bright spark decided to make an AD that had the attributes of both in a single pill. While the idea might be good on paper, vortioxetine hasn't exactly set the AD market on fire. I suspect the reason is the AD has a fixed ratio of the combined attributes whereas when adding buspirone to a SSRI there is are a wide range of possible ratios for fine tuning.

Which raises the question of is it worth continuing with vortioxetine, or would another AD be better? I don't know. It comes down to whether vortioxetine is not effective, or is it being inhibited by the diazepam?

I think taking the diazepam is more problematic than the pregabalin, but you really need to be talking with a psychiatrist about this, imo.

[1]
Boldrini M, Butt TH, Santiago AN, et al. (2014)
Benzodiazepines and the potential trophic effect of antidepressants on dentate gyrus cells in mood disorders.
Int J Neuropsychopharmacol. Dec;17(12):1923-33 (Abstract (https://www.ncbi.nlm.nih.gov/pubmed/24969726) | Full text (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4374628/))

Sun Y, Evans J, Russell B, et al (2013)
A benzodiazepine impairs the neurogenic and behavioural effects of fluoxetine in a rodent model of chronic stress.
Neuropharmacology. Sep;72:20-8 (Abstract (https://www.ncbi.nlm.nih.gov/pubmed/23639432))

Song J, Zhong C, Bonaguidi MA, et al (2012)
Neuronal circuitry mechanism regulating adult quiescent neural stem-cell fate decision.
Nature. Sep 6;489(7414):150-4 (Article (https://www.kurzweilai.net/how-the-brains-stem-cells-find-out-when-to-make-new-neurons/comment-page-1#comment-96481) | Study full text (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3438284/))

Wu X, Castren E. (2009)
Co-treatment with diazepam prevents the effects of fluoxetine on the proliferation and survival of hippocampal dentate granule cells.
Biol Psychiatry. Jul 1;66(1):5-8 (Abstract (https://www.ncbi.nlm.nih.gov/pubmed/19251245))

See also: the 'Ugly' part of Benzodiazepines: The Good, The Bad, and the Ugly (https://journalofpsychiatryreform.com/2016/11/20/benzodiazepines-the-good-the-bad-and-the-ugly/).

[SideFX]

[QUOTE=panic_down_under;2073634]How long after the last dose decrease did you begin having these symptoms, John?



Did he start you on all these meds, or a psychiatrist?
A psychiatrist did in whilst in hospital

Imo, there are two significant issues with your med regime. Firstly there's now good evidence1 that benzodiazepines both worsen anxiety in the longer run and reduce the effectiveness of serotonergic ADs. The second is that the diazepam and pregabalin are basically doling the same job, slow the 'firing' rate of neurons, albeit from different directions. Diazepam does it by increasing the inflow of negatively charged chlorine ions which makes it harder for a cell to raise its electrical voltage to the depolarization level. Pregabalin slows firing by decreasing the influx of positively charged calcium ions. I don't see the point of taking two meds to do the same thing. It would have been more efficient to just raise the dose of one of them.
Pregabalin did far more and continued without tolerance, the benzo did nothing after a few weeks, as is usual for benzos.

Which brings us to the other two. Despite what is says on the packaging, mirtazapine isn't a true AD, but a sedative so its main role in your case may be to help you sleep and it may reduce anxiety to some extent through sedation.
I agree mirtazipine is a very weak AD, but a strong antihistamine, however in combo with venlafaxine years ago, was my saviour

Vortioxetine combines the actions of a SSRI with that of buspirone (Buspar). It was noticed that buspirone can enhance the effectiveness of SSRIs and other serotonergic ADs and also ease some of their side-effects. So some bright spark decided to make an AD that had the attributes of both in a single pill. While the idea might be good on paper, vortioxetine hasn't exactly set the AD market on fire. I suspect the reason is the AD has a fixed ratio of the combined attributes whereas when adding buspirone to a SSRI there is are a wide range of possible ratios for fine tuning.
Not up to speed with this AD, just know I struggled to tolerate it and may still do, don’t know anymore

Which raises the question of is it worth continuing with vortioxetine, or would another AD be better? I don't know. It comes down to whether vortioxetine is not effective, or is it being inhibited by the diazepam?
Diazepam had no effect on my previous recover in 2012 and I discontinued it easily

I think taking the diazepam is more problematic than the pregabalin, but you really need to be talking with a psychiatrist about this, imo.
Okay thanks for your input anyway Ta John