Imipramine or Clomipramine

[SideFX]

Hi

Sorry this is so long but here goes

Mental health runs in my direct family and 2001 I fell into a pit of panic, anxiety and depression. The trigger was stress, as I had a young family and was made redundant and struggled to find another job.

I sunk soooo fast in a matter of weeks I was at rock bottom...Anyway I got offered a job and started on Peroxatine, after failing on just one dose of Prozac (Way too activating) And I consider my condition to be - Anxious, agitated depression. So I started work after being on Peroxatine for 2 weeks and after 6 or so weeks I was on top of the world and felt absolutely fantastic (I was a poster child for the med)

The only lasting side effect was on my libido. So after around 4 years I came off the med and started feeling off after about 3 months. So I started Peroxatine again, this time it kicked my anxiety through the roof. But I thought it kicked in last time, so I sucked it up and within 4/5 weeks felt fantastic again !!!

Another few years passed and I again came off my med, same reason as last time. And after a few months the old feelings were returning. So I reached for my Peroxatine again and the start up anxiety hit me. But I though I would be fine in 4/5 weeks. Well I was wrong as with each passing week I was sinking further and further until I felt like I was having seizures. So I went to my GP and they switched me to Citalopram and that rocketed my anxiety, by which time I was started on Diazipam to help me.

Anyway I did some research and heard that Venlafaxine was a good AD, so I asked to be switched to it and it had no effect, no side effects either. I was then referred to a psychiatrist who raised my Diazipam and kept raising Venlafaxine until I hit 375mg and couldn’t go higher...I was by now even deeper than ever before and losing touch with everything. The Pdoc tried a few add ons until we added Mirtazipine and I slept all night for the first time in months wow I wanted more. So we raised the Mirt to 30mg and Diazipam was at 25mg I used it PRN, so some days more some days less, but it always helped. Anyway after around 12-18 months I was well again and tapered off the Diazipam.

Again I still had low libido as an ongoing side effect. So in 2017 I tapered off Venlafaxine very slowly, as I was now better informed. Then the usual happened after a few months I started having panic anxiety and depression. I tried to start Venlafaxine again and my whole body went on fire I felt like I had really bad sunburn all over my body and the hot flashes were horrendous, albeit they were always a part of my anxiety symptom mix.

So began a search for meds to get me back to health...It started with a short spell on Doluxetine...Then 2 days on amitriptyline, but had a huge mega panic attack on day 2 with my heart rate going through the roof. Then back to a slower start up of Venlafaxine, but same reaction to both SNRI’s. I was not passed to the crisis team and secondary care with a psychiatrist...I ended up in hospital at this point and that was a waste of time as they switched me to Trazadone, even though I stated that my mum did well on imipramine and could I try that or Clomipramine.

I got out after about 6 weeks still in a mess and on Mirtazipine, Trazadone and Diazipam. My Pdoc tried many add ons like quitipine, lithium and lomotrigine. Non of which I could tolerate nor did they help...I ended up back in hospital and they took me off quitipine and Trazadone and put me on Brintellix/Trintellix with Lyrica.

Lyrica knocked me out and brintellix made the burning and hot flashes horrendous. I gave up in my mind, but had to fight for the sake of my family BTW I left my wife in 2012 and my son came to live with me he was 14.

I had to live and push myself for him and my sister whom I’m extremely close too...So anyway I’ve been out of hospital for over 2 years and got a new job 18months ago. I wanted to end it but carried on and have just recently changed jobs. I’m currently on:

Brintellix 20mg
Mirtazipine 30mg
Lyrica 600mg
Diazipam 10mg

I am suffering everyday, but I have focus to work, albeit I’m constantly on the edge of panic and feel like crying, which has become a big part of my condition this time (I never had it before) my symptom mix is the different, but the same if that makes sense !!!

Anyway I’ve done a lot of research on meds and self help and god knows I’m trying to carry on and put my life back together, but these meds just ain’t doing it for me. Now to the point, my mum was originally on an MAOI, then got took off that in the 80’s I think, she went through the wash out and then started Imipramine and was good after a few weeks on new med. she kept on with her 3mg of Lorazepam....So I’ve wondered if Imipramine might be good for me.

But I’m so frightened of going through more med switching and don’t want to lose everything I’ve worked so hard for...Its the tachycardia that scares me and the withdrawal from brintellix. Plus right now the risk it too high, as new job !!! But in the short term can’t suffer or tolerate how I am...I need help and the doctors are lost and they will go with whatever I want (Exept MOAI’s)

Any nuggets of wisdom would be soooo much appreciated please I know I won’t be able to carry on too much longer !! Thank you

[panic_down_under]

Another few years passed and I again came off my med, same reason as last time. And after a few months the old feelings were returning. So I reached for my Peroxatine again and the start up anxiety hit me. But I though I would be fine in 4/5 weeks. Well I was wrong as with each passing week I was sinking further and further until I felt like I was having seizures.

Your experience isn't unusual. There is now considerable evidence that ADs, especially the SSRIs, can become progressively less effective every time they are stopped and restarted, often requiring higher doses to achieve the previous level of control, or not working at all. They may also produce more severe, and/or different, initial side-effects. Two studies, Amsterdam JD (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5123793/), 2016 and Amsterdam JD (http://www.karger.com/Article/FullText/226611), 2009, found the likelihood of antidepressants working after each restart drops by between 19-25% (see also: Bosman RC (https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/30041180/), 2018; Amsterdam JD (http://www.ncbi.nlm.nih.gov/pubmed/18694599), 2009; Leykin Y (http://www.ncbi.nlm.nih.gov/pubmed/17469884), 2007; Paholpak S (https://www.ncbi.nlm.nih.gov/pubmed/12501907), 2002).


Anyway I did some research and heard that Venlafaxine was a good AD, so I asked to be switched to it and it had no effect, no side effects either. I was then referred to a psychiatrist who raised my Diazipam and kept raising Venlafaxine until I hit 375mg and couldn’t go higher...I was by now even deeper than ever before and losing touch with everything.

Despite what is says on the tin, venlafaxine is only a SSRI, not a SNRI, and has few advantages over the others and several significant disadvantages.

The other issue may have been the diazepam. Benzodiazepines (BZDs) may significantly reduce the effectiveness of antidepressants by blocking hippocampal neurogenesis which is how ADs create the therapeutic response (see: Boldrini M (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4374628/), 2014; Nochi R (https://www.ncbi.nlm.nih.gov/pubmed/23963779), 2013; --Sun Y (https://www.ncbi.nlm.nih.gov/pubmed/23639432), 2013; Song J (https://www.kurzweilai.net/how-the-brains-stem-cells-find-out-when-to-make-new-neurons/comment-page-1#comment-96481), 2012; Wu X (http://www.biologicalpsychiatryjournal.com/article/S0006-3223(09)00106-1/abstract), 2009; Stefovska VG (https://www.ncbi.nlm.nih.gov/pubmed/18991352), 2008).

In light of these studies benzodiazepines use should probably be limited to a couple of weeks when first taking antidepressants just to ease the initial increase in anxiety levels, for a while after AD dose increases for the same reason and thereafter for occasional breakthrough anxiety. If an antidepressant isn't adequately controlling anxiety on its own even at the maximum recommended or tolerated dose then switching to another which might be more effective should be considered ahead of supplementing it with a benzodiazepine.


I got out after about 6 weeks still in a mess and on Mirtazipine, Trazadone and Diazipam. My Pdoc tried many add ons like quitipine, lithium and lomotrigine. Non of which I could tolerate nor did they help...I ended up back in hospital and they took me off quitipine and Trazadone and put me on Brintellix/Trintellix with Lyrica.

Unfortunately, it is an all too often seen outcome once psychiatrists use up their personal small bag of tricks so resort to just throwing more and more drugs at the problem without rhyme, or reason in the usually vain hope that something will stick.


I’m currently on:

Brintellix 20mg
Mirtazipine 30mg
Lyrica 600mg
Diazipam 10mg

I am suffering everyday, but I have focus to work, albeit I’m constantly on the edge of panic and feel like crying, which has become a big part of my condition this time (I never had it before) my symptom mix is the different, but the same if that makes sense !!!

Vortioxetine (Brintellix, now Trintellix) is on paper a superior SSRI, but it hasn't set the world on fire. Mirtazapine is, as with venlafaxine, not what it claims on the tin. It is really only a sedative, not an antidepressant (and a powerful antihistamine). I don't understand the point of prescribing both pregabalin (Lyrica) and diazepam as they do the same thing, slowing neuron firing, albeit by different means. Diazepam does it by increasing the influx of negatively charged chlorine ions into cells which makes it harder for them to reach their depolarisation ('firing') voltage, pregabalin by inhibiting the ingress of positively charged calcium ions. There may be a rationale for preferring pregabalin over diazepam, but if you're also going to prescribe the BZD anyway then you might as well prescribe it at a high enough dose to do the job on its own as it is generally more effective than pregabalin.


Now to the point, my mum was originally on an MAOI, then got took off that in the 80’s I think, she went through the wash out and then started Imipramine and was good after a few weeks on new med. she kept on with her 3mg of Lorazepam....So I’ve wondered if Imipramine might be good for me.

I can't say whether imipramine will work for you, but the chances are pretty good. Imipramine was for many decades the 'gold standard' AD for panic disorder. Doctors now prefer to prescribe SSRIs and SNRIs because they are perceived to be safer in overdose, which isn't actually true of all of them, and to have fewer ongoing side-effects which is true, but often at the expense of more severe initial side-effects and harder withdrawals, not because they are more effective. TCAs are generally superior in performance, although, as with everything antidepressant, individual results may vary.


But I’m so frightened of going through more med switching and don’t want to lose everything I’ve worked so hard for..

From what you've written vortioxetine isn't actually doing that much so will you really lose anything by quitting? I suspect it's mainly the mirtazapine, pregabalin and diazepam doing the heavy lifting. You could continue to take them while waiting for the imipramine to kick-in.


.Its the tachycardia that scares me and the withdrawal from brintellix.

Did you had problems with tachycardia on venlafaxine? It is more cardio-toxic than the TCAs, except dosulepin. Imipramine was the first AD I took at doses of up to 350mg/day. Few doctors would prescribe that high a dose even for hospital inpatients, but my heart didn't care (still doesn't with the even more cardio toxic TCA (dosulepin) I'm now on despite being 30 years older).


I need help and the doctors are lost and they will go with whatever I want (Exept MOAI’s)

Why not a MAOI? They are generally the most effective ADs often working when nothing else will. There used to be issues with diet which is why I stopped taking phenelzine (Nardil) back in the day despite it being the best AD I've tried, but modern food processing techniques have eliminated most of the problems and adding a small supplementary dose of the TCA nortriptyline will block any blood-pressure spikes if one of the few remaining tyramine rich foods is inadvertently eaten. Should dosulepin ever poop-out on me the first thing I'll be trying is tranylcypromine (Parnate).

[SideFX]

Your experience isn't unusual. There is now considerable evidence that ADs, especially the SSRIs, can become progressively less effective every time they are stopped and restarted, often requiring higher doses to achieve the previous level of control, or not working at all. They may also produce more severe, and/or different, initial side-effects. Two studies, Amsterdam JD (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5123793/), 2016 and Amsterdam JD (http://www.karger.com/Article/FullText/226611), 2009, found the likelihood of antidepressants working after each restart drops by between 19-25% (see also: Bosman RC (https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/30041180/), 2018; Amsterdam JD (http://www.ncbi.nlm.nih.gov/pubmed/18694599), 2009; Leykin Y (http://www.ncbi.nlm.nih.gov/pubmed/17469884), 2007; Paholpak S (https://www.ncbi.nlm.nih.gov/pubmed/12501907), 2002).



Despite what is says on the tin, venlafaxine is only a SSRI, not a SNRI, and has few advantages over the others and several significant disadvantages.

The other issue may have been the diazepam. Benzodiazepines (BZDs) may significantly reduce the effectiveness of antidepressants by blocking hippocampal neurogenesis which is how ADs create the therapeutic response (see: Boldrini M (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4374628/), 2014; Nochi R (https://www.ncbi.nlm.nih.gov/pubmed/23963779), 2013; --Sun Y (https://www.ncbi.nlm.nih.gov/pubmed/23639432), 2013; Song J (https://www.kurzweilai.net/how-the-brains-stem-cells-find-out-when-to-make-new-neurons/comment-page-1#comment-96481), 2012; Wu X (http://www.biologicalpsychiatryjournal.com/article/S0006-3223(09)00106-1/abstract), 2009; Stefovska VG (https://www.ncbi.nlm.nih.gov/pubmed/18991352), 2008).

In light of these studies benzodiazepines use should probably be limited to a couple of weeks when first taking antidepressants just to ease the initial increase in anxiety levels, for a while after AD dose increases for the same reason and thereafter for occasional breakthrough anxiety. If an antidepressant isn't adequately controlling anxiety on its own even at the maximum recommended or tolerated dose then switching to another which might be more effective should be considered ahead of supplementing it with a benzodiazepine.



Unfortunately, it is an all too often seen outcome once psychiatrists use up their personal small bag of tricks so resort to just throwing more and more drugs at the problem without rhyme, or reason in the usually vain hope that something will stick.



Vortioxetine (Brintellix, now Trintellix) is on paper a superior SSRI, but it hasn't set the world on fire. Mirtazapine is, as with venlafaxine, not what it claims on the tin. It is really only a sedative, not an antidepressant (and a powerful antihistamine). I don't understand the point of prescribing both pregabalin (Lyrica) and diazepam as they do the same thing, slowing neuron firing, albeit by different means. Diazepam does it by increasing the influx of negatively charged chlorine ions into cells which makes it harder for them to reach their depolarisation ('firing') voltage, pregabalin by inhibiting the ingress of positively charged calcium ions. There may be a rationale for preferring pregabalin over diazepam, but if you're also going to prescribe the BZD anyway then you might as well prescribe it at a high enough dose to do the job on its own as it is generally more effective than pregabalin.



I can't say whether imipramine will work for you, but the chances are pretty good. Imipramine was for many decades the 'gold standard' AD for panic disorder. Doctors now prefer to prescribe SSRIs and SNRIs because they are perceived to be safer in overdose, which isn't actually true of all of them, and to have fewer ongoing side-effects which is true, but often at the expense of more severe initial side-effects and harder withdrawals, not because they are more effective. TCAs are generally superior in performance, although, as with everything antidepressant, individual results may vary.



From what you've written vortioxetine isn't actually doing that much so will you really lose anything by quitting? I suspect it's mainly the mirtazapine, pregabalin and diazepam doing the heavy lifting. You could continue to take them while waiting for the imipramine to kick-in.



Did you had problems with tachycardia on venlafaxine? It is more cardio-toxic than the TCAs, except dosulepin. Imipramine was the first AD I took at doses of up to 350mg/day. Few doctors would prescribe that high a dose even for hospital inpatients, but my heart didn't care (still doesn't with the even more cardio toxic TCA (dosulepin) I'm now on despite being 30 years older).



Why not a MAOI? They are generally the most effective ADs often working when nothing else will. There used to be issues with diet which is why I stopped taking phenelzine (Nardil) back in the day despite it being the best AD I've tried, but modern food processing techniques have eliminated most of the problems and adding a small supplementary dose of the TCA nortriptyline will block any blood-pressure spikes if one of the few remaining tyramine rich foods is inadvertently eaten. Should dosulepin ever poop-out on me the first thing I'll be trying is tranylcypromine (Parnate).

Thanks Ian

i take all your points and thank you so much for going to such trouble and detail in replying to each point in my post...Totally agree that Venlafaxine is basically an SSRI and I didn’t get tachycardia from it. It was like taking smarties and as you say I feel my body is now rejecting all SRI medication.

however I feel that as my mum did so well on the older AD’s MOAI’s and TCA’s that should be my direction of travel, starting with a decent TCA like imipramine and if it’s worked on a direct relative I’m hoping it will help me.

i also agree that Mirtazipine is basically a very potent antihistamine and barely touches Serotonin or Noradrenaline. Also with the ven and Mirt combo I was strong enough to tapper off 25mg Diazipam.

i also think your right in that brintellix is causing more problems and side effects than helping....However I’m scared and waiting to pull the trigger on that.

reason being I’ve just started a new job, but struggling to keep it all together!!!!
Thank you very much I hope you don’t mind me using this forum as my sounding board, till I take that leap of faith J

[panic_down_under]

I hope you don’t mind me using this forum as my sounding board, till I take that leap of faith J

Sure. This is what the forum is for.

[SideFX]

Sure. This is what the forum is for.

Thanks Ian

One thing I don’t understand is how the mechanism of action differs between SSRI’s and TCA’s and why this leads to less activating start up effects.

Also as anxiety is the major component of my depressive illness, is imipramine a good choice...I know it was the gold standard AD prior to the creation of SSRI’s and I’m familiar with Ken Gillman’s website too, which has been a good source of knowledge, albeit some of his stuff goes over my head. Especially when he gets into the biology

BTW
I do believe I suffer biological anxiety and depression, as it has responded to meds so well in the past. Would you agree will my thoughts on this point...Thank you very much

[panic_down_under]

One thing I don’t understand is how the mechanism of action differs between SSRI’s and TCA’s and why this leads to less activating start up effects.

It is partly due to the combination of receptors each effect in addition to the serotonin and noradrenaline/norepinephrine transporters and also TCA starting doses tend to be lower relative to their therapeutic range.


Also as anxiety is the major component of my depressive illness, is imipramine a good choice...I know it was the gold standard AD prior to the creation of SSRI’s

TCAs are generally a little more effective for anxiety and significantly more effective for depression than SSRIs. SSRIs are generally better at mitigating anxiety than depression...provided you can get past the initial heightened anxiety they often trigger.


I do believe I suffer biological anxiety and depression, as it has responded to meds so well in the past.

There is only biological anxiety and depression (and every other 'mental' illness, a term I dislike because it misleads folk). These disorders are the emotional manifestation of biological changes (PDF (https://www.americanscientist.org/sites/americanscientist.org/files/20057610584_306.pdf)) in the hippocampal regions of the brain caused by an auto-immune type response, not of the mind. The mind has no independent existence, it is a construct of the brain and so can't be independently diseased, or otherwise damaged. ADs reverse the hippocampal changes. So can the mind. Therapies such as CBT, REBT and mindfulness work by (https://doi.org/10.1016/j.biopsych.2013.05.017) the same process as ADs (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3025168/), neurogenesis.

[WiseMonkey]

I'm another who has done well on TCA's. I first had bad depression (and anxiety) in 1988, eight months after the birth of my second child but it was also the beginning of CFS (which I didn't know about at the time). It began when I couldn't sleep and I just got more and more run down and depressed. I didn't sleep for 4 months, then I changed Dr's and began on Prothiaden, which did nothing for me even at 100 mgs. I switched to Doxepin (75 mgs) and started sleeping after the third night then soon after that my depression started to lift. I was able to discontinue the AD's after a few months.
After I was diagnosed with CFS in 1995, I went back onto Doxepin 10mgs (the lowest dose) and have been on and off this med since then. Recently Doxepin was discontinued so I switched to Amtriptlyine 10mgs.

My Dr once tried me on an SSRI and I was climbing the walls with anxiety after one tablet! I decided then that they were not for me!

I'm quite sure my depression was triggered by the CFS (a neuroimmune/autoimmune disorder). It was interesting to read what your wrote about that in your post.

[SideFX]

It is partly due to the combination of receptors each effect in addition to the serotonin and noradrenaline/norepinephrine transporters and also TCA starting doses tend to be lower relative to their therapeutic range.



TCAs are generally a little more effective for anxiety and significantly more effective for depression than SSRIs. SSRIs are generally better at mitigating anxiety than depression...provided you can get past the initial heightened anxiety they often trigger.



There is only biological anxiety and depression (and every other 'mental' illness, a term I dislike because it misleads folk). These disorders are the emotional manifestation of biological changes (PDF (https://www.americanscientist.org/sites/americanscientist.org/files/20057610584_306.pdf)) in the hippocampal regions of the brain caused by an auto-immune type response, not of the mind. The mind has no independent existence, it is a construct of the brain and so can't be independently diseased, or otherwise damaged. ADs reverse the hippocampal changes. So can the mind. Therapies such as CBT, REBT and mindfulness work by (https://doi.org/10.1016/j.biopsych.2013.05.017) the same process as ADs (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3025168/), neurogenesis.

Again thank you Ian

I didn’t mention that the Brintellix has caused bruxism right from day one, but the Pregabalin masked it till it wore off (circa 6.5hr half life) Pdoc thinks that reducing Mirtazipine would help...I disagreed as Mirt has little to no affinity for serotonin.

But I was sick and tired of changing meds and have never felt that it truly helped over the past 2 plus years...I feel it has raised serotonin as you would expect it to do, but that has come at a cost of SideFX. I need a med that suits me, without the horrendous effects that SSRI’s give me and I’ve never properly tried a therapeutic dose of a TCA for a reasonable time.

I don’t really count 2 days on amitriptyline and they were with doluxatine, so that muddied the waters. And as my mum did so well for so many years on imipramine, after withdrawal from an MAOI, I don’t know why the Pdocs haven’t tried it...I’ve told him many times (They seem to be so passive) and state it’s not all about meds you know...Hey tell me something I don’t know, but when your fighting against your meds, there’s something wrong.

Also because I’m a high functioning person with depression and anxiety, they just pay lip service to our 3 monthly appointments. And point blank refuse Nardil or Parnate !!! But are happy to go with any TCA I suggest.

Thanks for all your little nuggets of knowledge and any more would be welcomed, particularly around imipramine thanks John

Ps
I know you were on imipramine for a number of years...I’ve read some previous posts. How did you find it and what condition(s) was it prescribed for ???? Many Thanks

[SideFX]

I'm another who has done well on TCA's. I first had bad depression (and anxiety) in 1988, eight months after the birth of my second child but it was also the beginning of CFS (which I didn't know about at the time). It began when I couldn't sleep and I just got more and more run down and depressed. I didn't sleep for 4 months, then I changed Dr's and began on Prothiaden, which did nothing for me even at 100 mgs. I switched to Doxepin (75 mgs) and started sleeping after the third night then soon after that my depression started to lift. I was able to discontinue the AD's after a few months.
After I was diagnosed with CFS in 1995, I went back onto Doxepin 10mgs (the lowest dose) and have been on and off this med since then. Recently Doxepin was discontinued so I switched to Amtriptlyine 10mgs.

My Dr once tried me on an SSRI and I was climbing the walls with anxiety after one tablet! I decided then that they were not for me!

I'm quite sure my depression was triggered by the CFS (a neuroimmune/autoimmune disorder). It was interesting to read what your wrote about that in your post.

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

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

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

[WiseMonkey]

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

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

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

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

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

[panic_down_under]

I didn’t mention that the Brintellix has caused bruxism right from day one

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


I feel it has raised serotonin as you would expect it to do, but that has come at a cost of SideFX.

SSRIs may not be doing what you think they do: Serotonin - The 'chemical imbalance' myth (http://www.nomorepanic.co.uk/showthread.php?t=193671)


I don’t really count 2 days on amitriptyline and they were with doluxatine, so that muddied the waters.

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


And as my mum did so well for so many years on imipramine, after withdrawal from an MAOI, I don’t know why the Pdocs haven’t tried it...I’ve told him many times (They seem to be so passive) and state it’s not all about meds you know...

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


Also because I’m a high functioning person with depression and anxiety, they just pay lip service to our 3 monthly appointments. And point blank refuse Nardil or Parnate !!! But are happy to go with any TCA I suggest.

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

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


I know you were on imipramine for a number of years...I’ve read some previous posts. How did you find it and what condition(s) was it prescribed for ???? Many Thanks

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

[panic_down_under]

I'm quite sure my depression was triggered by the CFS (a neuroimmune/autoimmune disorder)

Depression (also anxiety disorders) are the product of an auto-immune type reaction so your are almost certainly correct. Patients prescribed immune system boosting meds such as interferon (http://www.hepmag.com/articles/hepatitis_interferon_depression_2501_22378.shtml) to treat viral diseases and cancers they are now often also routinely prescribed an AD because of this. Immune system proteins may also reduce the effectiveness (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3337012/) of antidepressants.

See also:


Interferon-Related Depression: A Primer on Mechanisms, Treatment, and Prevention of a Common Clinical Problem (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5050402/)

A Dialogue between the Immune System and Brain, Spoken in the Language of Serotonin (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3547518/)

Is Depression An Infectious Disease? (https://www.popsci.com/depression-infectious-disease/)

Could depression be caused by our immune system? (https://www.mqmentalhealth.org/posts/could-depression-be-caused-by-our-immune-system)

[WiseMonkey]

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

[SideFX]

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

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

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

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

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

[SideFX]

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



SSRIs may not be doing what you think they do: Serotonin - The 'chemical imbalance' myth (http://www.nomorepanic.co.uk/showthread.php?t=193671)



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



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



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

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



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

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

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

Thanks for all your wisdom and pure nuggets John.

[WiseMonkey]

Depression (also anxiety disorders) are the product of an auto-immune type reaction so your are almost certainly correct. Patients prescribed immune system boosting meds such as interferon (http://www.hepmag.com/articles/hepatitis_interferon_depression_2501_22378.shtml) to treat viral diseases and cancers they are now often also routinely prescribed an AD because of this. Immune system proteins may also reduce the effectiveness (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3337012/) of antidepressants.

See also:

Interferon-Related Depression: A Primer on Mechanisms, Treatment, and Prevention of a Common Clinical Problem (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5050402/)

A Dialogue between the Immune System and Brain, Spoken in the Language of Serotonin (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3547518/)

Is Depression An Infectious Disease? (https://www.popsci.com/depression-infectious-disease/)

Could depression be caused by our immune system? (https://www.mqmentalhealth.org/posts/could-depression-be-caused-by-our-immune-system)


Thanks for the info. Some with overactive immune systems take immuno-suppressants eg Plaquinel or Methotrexate and often take a low dose TCA like Amitriptyline as it's good for pain and helps with sleep.

[panic_down_under]

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

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


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

Nope. Noradrenergic (NA) ADs work by the same mechanism as the serotonergic (5-HT) ones, stimulating the growth of new hippocampal brain cells, possibly by their effect on gene expression (https://pubmed.ncbi.nlm.nih.gov/23026812/). The genes affected seem to differ between NA and 5-HT reuptake inhibitors, but the end result is the same. Or it could be something completely different. That neurogenesis is the mechanism which produces the therapeutic response is pretty much settled science, how it is achieved is still poorly understood.


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

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

[SideFX]

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



Nope. Noradrenergic (NA) ADs work by the same mechanism as the serotonergic (5-HT) ones, stimulating the growth of new hippocampal brain cells, possibly by their effect on gene expression (https://pubmed.ncbi.nlm.nih.gov/23026812/). The genes affected seem to differ between NA and 5-HT reuptake inhibitors, but the end result is the same. Or it could be something completely different. That neurogenesis is the mechanism which produces the therapeutic response is pretty much settled science, how it is achieved is still poorly understood.



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

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

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

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

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

[panic_down_under]

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

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


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

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


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

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

[SideFX]

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



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



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

Thanks Ian

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

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

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

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

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

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

[panic_down_under]

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

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



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

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


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

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


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

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

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


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

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

[SideFX]

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



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



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



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

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



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

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

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

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

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

[panic_down_under]

I thought if I force my body to accept it it would resolve itself

Unfortunately, that isn't how these things work. If a side-effect continue to persist beyond when the med kicks-in then it will likely continue as long as you're on it though some degree of tolerance may slowly develop.


My concern is that the Neuropathy becomes permanent and won’t fade once I switch to a TCA med...I’ve asked my GP the question and also the bruxism and she will not commit herself or even say there is a good chance (Talk about sitting on the fence)

She was probably right to do so as there is not much data to go on. My gut feeling is that it will resolve as soon as you stop taking vortioxetine, but I can't guarantee it. Nerves are tricky.


When I was put on quetiapine I would get vibrations in my legs and body and feel disoriented upon waking...This has faded, but still plagues me after more than 2 years. Again I have spoke to my Pdoc, who is completely disinterested...I feel I did something to my dopamine receptors for sure...

The receptors themselves, no. Receptors (and transporters) are simple protein molecules which have limited half-lives, minutes to a few days depending on where they are in the brain (or elsewhere in the nervous system) and how often they are activated. My guess is that your current problem relates to the mirtazapine. There's not a lot of difference in the receptors they both target, although mirtazapine is an even weaker binder to dopamine D1 and D2 receptors than quetiapine:


Mirtazapine: H1: 1.6 Ki, 5-HT2a: 69.0 Ki, D1: 4100 Ki, D2: 1000 Ki,
Quetiapine : H1: 6.9 Ki, 5-HT2a: 118. Ki, D1: 712. Ki, D2: 500.0 Ki

[SideFX]

Unfortunately, that isn't how these things work. If a side-effect continue to persist beyond when the med kicks-in then it will likely continue as long as you're on it though some degree of tolerance may slowly develop.



She was probably right to do so as there is not much data to go on. My gut feeling is that it will resolve as soon as you stop taking vortioxetine, but I can't guarantee it. Nerves are tricky.



The receptors themselves, no. Receptors (and transporters) are simple protein molecules which have limited half-lives, minutes to a few days depending on where they are in the brain (or elsewhere in the nervous system) and how often they are activated. My guess is that your current problem relates to the mirtazapine. There's not a lot of difference in the receptors they both target, although mirtazapine is an even weaker binder to dopamine D1 and D2 receptors than quetiapine:


Mirtazapine: H1: 1.6 Ki, 5-HT2a: 69.0 Ki, D1: 4100 Ki, D2: 1000 Ki,
Quetiapine : H1: 6.9 Ki, 5-HT2a: 118. Ki, D1: 712. Ki, D2: 500.0 Ki

Thanks Ian that puts my mind to rest regarding the receptors and that no permanent damage could be caused...Still doesn’t explain the reaction and it’s continued effects, albeit to a lesser degree

Can I pick your brains about Pregabalin, as I’ve read so many horror stories about its addictive and tolerance effects ??? Also it can be associated with causing depression and anxiety????

My roadmap hopefully is to swap out the Brintellix for imipramine and hopefully gel well with the TCA...Then when I hopefully feel stable enough. Taper Pregabalin first then Diazipam and think about the Mirtazipine (Which is acting mostly as an antihistamine) plus my tolerance to it is very high after 10 years use.

I would so love to go back to a mono therapeutic solution...Right now I can only wish for it and plan the right time to take that risk.

I’ve searched on brintellix and it’s a real mixed bag of being fantastic, to its the worst med I’ve ever taken. Plus as it kinda overlaps as busper - I don’t get why I’ve got bruxism from it, as busper is a known med to resolve bruxism????

Your thoughts please (I really need to get out of this poly drugged situation) Ta John

[panic_down_under]

Still doesn’t explain the reaction and it’s continued effects, albeit to a lesser degree

I think it's coming from the mirtazapine, John. It targets most of the same receptors as quetiapine to similar degrees.


Can I pick your brains about Pregabalin, as I’ve read so many horror stories about its addictive and tolerance effects ??? Also it can be associated with causing depression and anxiety????

There's a lot of evidence for it triggering depression, anxiety to a lesser extent. Imho, the only advantage pregabalin (and gabapentin) have over BZDs is that they don't inhibit neurogenesis and there is some evidence they speed up the maturation of new neurons a little although they don't seem to increase their numbers. I put pregabalin well down the list of meds to try for anxiety. I don't think there is any place for gabapentin now that pregabalin generics are available, mostly because of the way its bioavailability drops rapidly as the dose increases. You end up taking a lot more drug for little extra activity.


My roadmap hopefully is to swap out the Brintellix for imipramine and hopefully gel well with the TCA...Then when I hopefully feel stable enough. Taper Pregabalin first then Diazipam and think about the Mirtazipine (Which is acting mostly as an antihistamine) plus my tolerance to it is very high after 10 years use.

This is a reasonable plan.


I’ve searched on brintellix and it’s a real mixed bag of being fantastic, to its the worst med I’ve ever taken.

To be fair you'll find the same for every psyche med, and many other meds too. It isn't really a commentary about the med as such, but about how the med meshes with individual biology. No AD is intrinsically any better than another, but some may be for an individual. The hard part is determining which ones work best as trial and error is the only conclusive test.


Plus as it kinda overlaps as busper - I don’t get why I’ve got bruxism from it, as busper is a known med to resolve bruxism????

Vortioxetine is a much weaker 5-HT1a receptor agonist than buspirone. I suspect it it is too weak to have any real therapeutic benefit which might be why the med hasn't been the success the developers hoped for. Vilazodone (Viibryd) which another of the new combined SSRI+5-HT1a agonists hasn't really taken off either despite being a more potent 5-HT1a agonist. Far better imo to take an ordinary SSRI and add buspirone to it if necessary at a high enough dose to make a difference. I really don't understand why doctors switch patients from another SSRI to vortioxetine without first supplementing the current med with buspirone first given how much easier this usually is on the patient.

[SideFX]

I think it's coming from the mirtazapine, John. It targets most of the same receptors as quetiapine to similar degrees.



There's a lot of evidence for it triggering depression, anxiety to a lesser extent. Imho, the only advantage pregabalin (and gabapentin) have over BZDs is that they don't inhibit neurogenesis and there is some evidence they speed up the maturation of new neurons a little although they don't seem to increase their numbers. I put pregabalin well down the list of meds to try for anxiety. I don't think there is any place for gabapentin now that pregabalin generics are available, mostly because of the way its bioavailability drops rapidly as the dose increases. You end up taking a lot more drug for little extra activity.



This is a reasonable plan.



To be fair you'll find the same for every psyche med, and many other meds too. It isn't really a commentary about the med as such, but about how the med meshes with individual biology. No AD is intrinsically any better than another, but some may be for an individual. The hard part is determining which ones work best as trial and error is the only conclusive test.



Vortioxetine is a much weaker 5-HT1a receptor agonist than buspirone. I suspect it it is too weak to have any real therapeutic benefit which might be why the med hasn't been the success the developers hoped for. Vilazodone (Viibryd) which another of the new combined SSRI+5-HT1a agonists hasn't really taken off either despite being a more potent 5-HT1a agonist. Far better imo to take an ordinary SSRI and add buspirone to it if necessary at a high enough dose to make a difference. I really don't understand why doctors switch patients from another SSRI to vortioxetine without first supplementing the current med with buspirone first given how much easier this usually is on the patient.

Again thanks for the greater insight to these meds.
I must agree that Pregabalin doesn’t work any better at higher doses and taken along with Diazipam can and do potentiate the sedative effects, which isn’t tackling the problem, just making you really really sleepy as it peaks after around 2/3 hours.


I’m sure I tried buspar during my 2010 meltdown and it just made me so so angry, I had to stop it straight away.

I just don’t feel the vortioxatine is doing its thing and I’ve tried to force my body to accept it, which has led to a greater tolorance to its SideFX but I’m still in a funk and with denial that depression can be resolved by meds from my Pdoc, has left me tired and exhausted...All I want is my mojo back and I feel that’s a matter of finding the right med again !!!!

As you have stated it’s a clinical state and therefore requires a clinical solution and that is the right med at the right dose.

I’ve also read that you can stop Brintellix abruptly at 10mg oh yeah and I believe that a med altering brain chemistry can just be stopped like that (No way) your thoughts please Ian ???

The passive approach of my doctors has been the reason I’ve not hit the right med and my exhaustion at switching meds a couple of years ago...But I know if I don’t then I will end up going down the road my father did. He took his life in 93 !!!! Thank you Ian I appreciate your knowledge and continued support Ta John

[pulisa]

My son has been on vortioxetine for about 3 moths at 20mg daily and it's made no difference at all..he's also on quetiapine 400mg and 1mg lorazepam twice daily. He's been on loads of other ADs and been hospitalised twice.

One psychiatrist told him that TCAs worked better in men but that opinion wasn't shared by other psychs.

It's all a lottery, John but I wish you all the very best with your recovery. It helps so much to be proactive and to challenge the psychs every inch of the way if you are not happy with their prescribing.

[SideFX]

My son has been on vortioxetine for about 3 moths at 20mg daily and it's made no difference at all..he's also on quetiapine 400mg and 1mg lorazepam twice daily. He's been on loads of other ADs and been hospitalised twice.

One psychiatrist told him that TCAs worked better in men but that opinion wasn't shared by other psychs.

It's all a lottery, John but I wish you all the very best with your recovery. It helps so much to be proactive and to challenge the psychs every inch of the way if you are not happy with their prescribing.

Thanks Pulisa...I totally agree it’s like playing Russian roulette to spin the barrel, pull the trigger and hope for the best...I’ve never really dabbled with TCA’s however I know I cannot tolerate SRI meds any more, as the SideFX just hurt...So I’ve ended up taking one med to try and dampen the effects of another and led to a poly drugged situation.

But still no remission...I wish your son the best and a speedy recovery. I got lucky first time with Peroxatine which was lovely and then again with Venlafaxine, again led me back to my old self. So I know meds work and I’ve seen it with my mum.

It’s just hard going through each trial and then to start over again, it’s very tough

Thank you John

[panic_down_under]

I’m sure I tried buspar during my 2010 meltdown and it just made me so so angry, I had to stop it straight away.

Anger/hostility is a listed side-effect, but I haven't heard of anyone experiencing this until now. Most have no side-effects...or response. Did you take it on its own, or with an AD?


As you have stated it’s a clinical state and therefore requires a clinical solution and that is the right med at the right dose.

The cognitive/behavioural/mindfulness therapies can also be very effective. They work by the same mechanism as ADs.


I’ve also read that you can stop Brintellix abruptly at 10mg oh yeah and I believe that a med altering brain chemistry can just be stopped like that (No way)

I'd drop the dose to 5mg for 14 days and then quit, if that is the way you want to do it. Alternatively you could talk to your GP about adding 25-50mg imipramine at week 2.

[pulisa]

Thanks Pulisa...I totally agree it’s like playing Russian roulette to spin the barrel, pull the trigger and hope for the best...I’ve never really dabbled with TCA’s however I know I cannot tolerate SRI meds any more, as the SideFX just hurt...So I’ve ended up taking one med to try and dampen the effects of another and led to a poly drugged situation.

But still no remission...I wish your son the best and a speedy recovery. I got lucky first time with Peroxatine which was lovely and then again with Venlafaxine, again led me back to my old self. So I know meds work and I’ve seen it with my mum.

It’s just hard going through each trial and then to start over again, it’s very tough

Thank you John

Psychiatrists use these drugs like broad spectrum antibiotics. It would be great if in the future a brain scan could prescribe the right med at the right dose and do away with human guesswork altogether but I doubt whether this would be in our lifetimes!! You've had success with some ADs-as has your Mum and psychs are quite hot on family history on these meds-so there is every hope that you will find the right combo in time..but the "in time" bit is always the hard bit to tolerate!

[SideFX]

Anger/hostility is a listed side-effect, but I haven't heard of anyone experiencing this until now. Most have no side-effects...or response. Did you take it on its own, or with an AD?



The cognitive/behavioural/mindfulness therapies can also be very effective. They work by the same mechanism as ADs.



I'd drop the dose to 5mg for 14 days and then quit, if that is the way you want to do it. Alternatively you could talk to your GP about adding 25-50mg imipramine at week 2.

Thanks Ian

I am a bit fuzzy bout the buspar, could of been Wellbutrin that made me so angry. I took it with venlafaxine at the time.

I personally find that the CBT and other cognitive therapies are of no use to me....The only thing that has helped has been Pharmacologic and tenacity!!!

I have started trying CBD Oil and don’t know if it’s placebo effect, but it does help...I need to be careful though as my second dose of Pregabalin with Diazipam can knock me out like a tranqulliser dart. I take them 6 hours apart and this has always been the case. It’s as if the peak is delayed for several hours and as I’m coming down of it I can feel it bad.

I was thinking of trying again to taper the Pregabalin, as I’ve tried and failed twice (Your thoughts Ian ?)

I totally agree with you in regards of the vortioxatine, with the M.O. of drop to 5mg and cross taper for 2 weeks with a small dose of imipramine. I so need all of the above to work out for me, as I have so much hanging on it...My work and my livelihood!!!!!

Any further guidance Ta John

[SideFX]

Psychiatrists use these drugs like broad spectrum antibiotics. It would be great if in the future a brain scan could prescribe the right med at the right dose and do away with human guesswork altogether but I doubt whether this would be in our lifetimes!! You've had success with some ADs-as has your Mum and psychs are quite hot on family history on these meds-so there is every hope that you will find the right combo in time..but the "in time" bit is always the hard bit to tolerate!

Thanks Pilisa
Yeah it is not a science, albeit the pdocs act like it is, they have no idea how exactly these meds work and that makes it even more difficult...You would have thought that they would follow the family response indicator, however that’s not the case.

As PDU has stated they go with what they’ve used recently and have a toolbox of meds to try...Then when that’s exhausted they are lost and don’t listen to the patient...For gods sake, surely that’s the starting point and not the last resort, which is what had happened in my case...I have asked for it numerous times and put on meds that don’t suit or do nothing !!!!

There is a gene test but I believe it’s very far from accurate and therefore not worth wasting money on...What AD’s has your son been through and is this his first episode ???? Ta John

[panic_down_under]

I am a bit fuzzy bout the buspar, could of been Wellbutrin that made me so angry. I took it with venlafaxine at the time.

Bupropion (Wellbutrin) is a very stimulating AD so would be more likely to trigger anger I would have thought, although it is a listed side-effect of both meds. Not a med most with anxiety can tolerate as it can almost literally have them climbing the walls, but small adjuvant doses to counter AD induced weight gain, or for sexual dysfunction can be useful, however, buspirone is often effective for the latter so the better initial option.


I personally find that the CBT and other cognitive therapies are of no use to me...

Unfortunately, therapy didn't help me either, but I did enjoy the sessions.


I have started trying CBD Oil and don’t know if it’s placebo effect, but it does help...

It can be, however, cannabis isn't as THC has the same deleterious effects on hippocampal neurons as alcohol, BZDs and cortisol.


I need to be careful though as my second dose of Pregabalin with Diazipam can knock me out like a tranqulliser dart. I take them 6 hours apart and this has always been the case. It’s as if the peak is delayed for several hours and as I’m coming down of it I can feel it bad.

Interesting. The amount of diazepam in your system wouldn't vary much across 24 hours. Pregabalin's may if you're a fast metaboliser because of its short half life


I was thinking of trying again to taper the Pregabalin, as I’ve tried and failed twice

The problem can be that short half-life because it can drop out of the system very quickly especially at the lower doses which may set up a roller-coaster effect which many find very disturbing. Upping the diazepam dose may help, but your GP may take some convincing given you're on a largish dose already.


I totally agree with you in regards of the vortioxatine, with the M.O. of drop to 5mg and cross taper for 2 weeks with a small dose of imipramine. I so need all of the above to work out for me, as I have so much hanging on it...My work and my livelihood!!!!!

You need to get your GP's and particularly your psychiatrist's inputs on this too. On paper it should be fine, but these things all come down to YMMV, and they are better placed to foresee any likely pitfalls based on your general well-being and history.

[SideFX]

Bupropion (Wellbutrin) is a very stimulating AD so would be more likely to trigger anger I would have thought, although it is a listed side-effect of both meds. Not a med most with anxiety can tolerate as it can almost literally have them climbing the walls, but small adjuvant doses to counter AD induced weight gain, or for sexual dysfunction can be useful, however, buspirone is often effective for the latter so the better initial option.



Unfortunately, therapy didn't help me either, but I did enjoy the sessions.



It can be, however, cannabis isn't as THC has the same deleterious effects on hippocampal neurons as alcohol, BZDs and cortisol.



Interesting. The amount of diazepam in your system wouldn't vary much across 24 hours. Pregabalin's may if you're a fast metaboliser because of its short half life



The problem can be that short half-life because it can drop out of the system very quickly especially at the lower doses which may set up a roller-coaster effect which many find very disturbing. Upping the diazepam dose may help, but your GP may take some convincing given you're on a largish dose already.



You need to get your GP's and particularly your psychiatrist's inputs on this too. On paper it should be fine, but these things all come down to YMMV, and they are better placed to foresee any likely pitfalls based on your general well-being and history.

Thanks Ian

Would you consider dropping Pregabalin albeit extremely slowly or hang out for the swap to a TCA and hopefully getting more stability before attempting any med reductions ??? I know it’s a big question and one that’s been plaguing me for months and months...You said you thought that Pregabalin and diazipam were probably what we’re giving me the lift, with very little help from brintellix.

Do you mind explaining in greater detail what you were referring too with that response please ???? Ta John

BTW
I’m pretty sure if was Wellbutrin as it fits the pattern and validates what bits I’ve read about the med

[panic_down_under]

Would you consider dropping Pregabalin albeit extremely slowly or hang out for the swap to a TCA and hopefully getting more stability before attempting any med reductions ???

Leave it until after you're stabilised on imipramine as it may help with any anxiety spike at the beginning. Getting onto an effective AD should be the priority. Whatever issues there are with pregabalin and diazepam are probably not going to get any worse over the next month or two given you've been on both for years.


You said you thought that Pregabalin and diazipam were probably what we’re giving me the lift, with very little help from brintellix.

That does seem to be the case from what you've posted, John.


Do you mind explaining in greater detail what you were referring too with that response please ????

About pregabalin and diazepam, vortioxetine, or something else? Sorry, I don't know which response you're referring to.

[SideFX]

Leave it until after you're stabilised on imipramine as it may help with any anxiety spike at the beginning. Getting onto an effective AD should be the priority. Whatever issues there are with pregabalin and diazepam are probably not going to get any worse over the next month or two given you've been on both for years.



That does seem to be the case from what you've posted, John.



About pregabalin and diazepam, vortioxetine, or something else? Sorry, I don't know which response you're referring to.


Sorry Ian

I was referring to more details around your comment that Pregabalin and Diazipam we’re probably providing the lift and vortioxatine wasn’t really doing much if anything, albeit I asked if it’s raising serotonin levels it must be doing something...The vortioxatine however comes with a host of SideFX for me ???

Hope that makes sense and I think your probably correct, in trying to get on an AD that I gel with first...Even though it all scares the crap out of me TBH I have had so many med changes but cannot tolerate the SRI’s any more. So I hope the TCA class is a better fit

Thanks Ian Ta John

[panic_down_under]

I was referring to more details around your comment that Pregabalin and Diazipam we’re probably providing the lift and vortioxatine wasn’t really doing much if anything, albeit I asked if it’s raising serotonin levels it must be doing something...The vortioxatine however comes with a host of SideFX for me ???

Yep, pregabalin, diazepam and mirtazapine based on what you've posted, John. Whatever positive effect vortioxetine may be having seems likely cancelled by the impact of the side-effects on your psyche. In your first post you wrote that you're almost constantly on the verge of panic. Whatever issues there may be with the other three they are pretty consistent in their performance which suggests it's the AD pulling you down. What is your take?

[SideFX]

Yep, pregabalin, diazepam and mirtazapine based on what you've posted, John. Whatever positive effect vortioxetine may be having seems likely cancelled by the impact of the side-effects on your psyche. In your first post you wrote that you're almost constantly on the verge of panic. Whatever issues there may be with the other three they are pretty consistent in their performance which suggests it's the AD pulling you down. What is your take?

Hi Ian

I do feel on the edge and the slightest bump hurts me, a bit like driving a car with flat tyres, you feel every bump in the road and it’s magnified....Albeit I do experience degrees of diurnal variation, some days more so than others and as I said early on I seem to have the ability to focus, with less cog fog than previous meds.

However this comes at a price of skin burning sensations, hot flashes, palps, shortness of breath, fatigue, guilt, depression, bruxism and so on...I obviously have built some tolerance to these effects, but after nearly 2 plus years, I should be in full remission and that’s my take on it.

I therefore need to navigate my way through this poly drugged path and try to mitigate as much as possible any additional risk of med changes. Cause this combo is not the right path and I’m sure of that...What I’m not sure of is which med and where to start a new journey. Sorry if this all sounds a bit airy fairy and flakey, but I’m hoping to try and put someone in my shoes.

The risks as I said are very high in my opinion and is this a true quality of life NO NO NO !!!!

I’ve told my GP and Pdoc that the bruxism has me biting my tongue and that hurts, added to which my jaw and teeth still hurt and feel sore. But are they offering any solutions again NO NO NO. I don’t count the advise of reducing Mirtazipine to resolve the bruxism...That’s crap and the only proven method of resolving bruxism is to add buspar, or withdraw the offending med !!!! That’s fact.

I am gonna ask my GP if she can arrange a second opinion. Not a diagnosis, I don’t need that - I mean a proper psychiatric look at my meds and offer some way forward and I don’t mean adding stupid AP meds or Mood Stabilisers. I need an AD that fits me like Peroxatine and venlafaxine have in the past.

Sorry for the rant Ian Ta John

[panic_down_under]

I am gonna ask my GP if she can arrange a second opinion. Not a diagnosis, I don’t need that - I mean a proper psychiatric look at my meds and offer some way forward and I don’t mean adding stupid AP meds or Mood Stabilisers. I need an AD that fits me like Peroxatine and venlafaxine have in the past.

A good idea, imho. But if you're expecting a definitive answer of "this med is *the* one" you probably won't get it, or at least you shouldn't. Imipramine may, or not be the right AD for you, and this is just as true of all the others. Unfortunately, the only reliable method of finding the best AD fit is by trial and error. And part of that is not automatically ruling anything out such as the MAOIs as some of your doctors apparently have. However, it is reasonable to put meds with issues such as most SNRIs, antipsychotics and antiepileptics toward the bottom of the list.

[SideFX]

A good idea, imho. But if you're expecting a definitive answer of "this med is *the* one" you probably won't get it, or at least you shouldn't. Imipramine may, or not be the right AD for you, and this is just as true of all the others. Unfortunately, the only reliable method of finding the best AD fit is by trial and error. And part of that is not automatically ruling anything out such as the MAOIs as some of your doctors apparently have. However, it is reasonable to put meds with issues such as most SNRIs, antipsychotics and antiepileptics toward the bottom of the list.

Thanks Ian

I totally get that there are no guarantees that any particular med may or may not suit each individual and that’s a trial and error process...But it is surely the doctors obligation and goal to get the patient back to feeling how they used too !!!

And I feel my doctors are all being to passive and particularly my Pdoc who doesn’t believe that meds are the answer and keeps trying to play the phycologist with me...I don’t need that I need someone who has the goal of getting my life back and not sitting on the fence, with no suggestions. It’s me that’s driving the bus and it should be them.

They should be saying okay we should try this and if that doesn’t work then that and have a medication plan, at least for the next couple of stages and as you say all AD’s must be explored before resorting to any off label uses of other meds. And I need a fresh pair of eyes to look at things and listen to me.

This morning was so bad I could have easily turned the lights out for good...What I don’t understand is this time round I’ve cried so so much, however no previous episode has triggered that in me, which makes me feel something has definitely changed but what ??? Any ideas Ian and why do I react so badly to SSRI/SNRI meds ???

I’m losing hope because the doctors just ain’t seeing the gravity of the situation I’m in !!!!

Thanks Ian

[SideFX]

Thanks Ian

I totally get that there are no guarantees that any particular med may or may not suit each individual and that’s a trial and error process...But it is surely the doctors obligation and goal to get the patient back to feeling how they used too !!!

And I feel my doctors are all being to passive and particularly my Pdoc who doesn’t believe that meds are the answer and keeps trying to play the phycologist with me...I don’t need that I need someone who has the goal of getting my life back and not sitting on the fence, with no suggestions. It’s me that’s driving the bus and it should be them.

They should be saying okay we should try this and if that doesn’t work then that and have a medication plan, at least for the next couple of stages and as you say all AD’s must be explored before resorting to any off label uses of other meds. And I need a fresh pair of eyes to look at things and listen to me.

This morning was so bad I could have easily turned the lights out for good...What I don’t understand is this time round I’ve cried so so much, however no previous episode has triggered that in me, which makes me feel something has definitely changed but what ??? Any ideas Ian and why do I react so badly to SSRI/SNRI meds ???

I’m losing hope because the doctors just ain’t seeing the gravity of the situation I’m in !!!!

Thanks Ian

Another thing is I don’t understand the neuropathic effects that SRI meds are having on me, it’s my skin and all manner of neuropathic sensations and why won’t the doctors believe me...Any ideas Ian ??? Ta John

[panic_down_under]

Another thing is I don’t understand the neuropathic effects that SRI meds are having on me, it’s my skin and all manner of neuropathic sensations and why won’t the doctors believe me.

I have no idea why they don't believe you. Most SSRIs have them as listed potential side-effects. The list for vortioxetine includes pruritus (severe itching), formication (feeling of insects crawling on skin), redness of the face, neck and arms, hyperhidrosis (excess sweating irrespective of temperature), flushing/hot flushes/flashing, night sweats, rashes, angioedema (large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs which may extend deep into the skin).

Bruxism is also on the list, as it is for all SSRIs. It is hardly a new finding. Studies about it began appearing soon after SSRIs became available, for example this one from 1995 co authored by David Healy - PDF. (https://davidhealy.org/wp-content/uploads/2012/05/1995-Dystonias-and-dyskinesias-of-the-jaw.pdf)

[SideFX]

I have no idea why they don't believe you. Most SSRIs have them as listed potential side-effects. The list for vortioxetine includes pruritus (severe itching), formication (feeling of insects crawling on skin), redness of the face, neck and arms, hyperhidrosis (excess sweating irrespective of temperature), flushing/hot flushes/flashing, night sweats, rashes, angioedema (large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs which may extend deep into the skin).

Bruxism is also on the list, as it is for all SSRIs. It is hardly a new finding. Studies about it began appearing soon after SSRIs became available, for example this one from 1995 co authored by David Healy - PDF. (https://davidhealy.org/wp-content/uploads/2012/05/1995-Dystonias-and-dyskinesias-of-the-jaw.pdf)

Thanks Ian

For believing and validating these heat and hot burning flashes, as SideFX of AD’s...I’ve read that these are less likely with other types of AD’s

Could you kindly explain in very simple terms how the mechanism of actions between SSRI’s and TCA’s differ please ??? Many thanks John

[panic_down_under]

Could you kindly explain in very simple terms how the mechanism of actions between SSRI’s and TCA’s differ please

The SSRIs all are primarily inhibitors of serotonin reuptake. The TCAs vary a lot in their actions, but generally inhibit reuptake of both serotonin (5-HT) and noradrenaline/norepinephrine (NA) to significant degrees. Some such as imipramine, amitriptyline and clomipramine are biased to inhibiting 5-HT more than NA, others such as desipramine and nortriptyline inhibit NA reuptake more than 5-HT. They also tend to target a greater range of other receptors more than the SSRIs do which seems to improve their effectiveness, but the downside to this is they also impact receptors such as histamine HI and muscarinic acetylcholine which produce ongoing side-effects such as sedation and dry mouth and constipation.

[SideFX]

The SSRIs all are primarily inhibitors of serotonin reuptake. The TCAs vary a lot in their actions, but generally inhibit reuptake of both serotonin (5-HT) and noradrenaline/norepinephrine (NA) to significant degrees. Some such as imipramine, amitriptyline and clomipramine are biased to inhibiting 5-HT more than NA, others such as desipramine and nortriptyline inhibit NA reuptake more than 5-HT. They also tend to target a greater range of other receptors more than the SSRIs do which seems to improve their effectiveness, but the downside to this is they also impact receptors such as histamine HI and muscarinic acetylcholine which produce ongoing side-effects such as sedation and dry mouth and constipation.

Hi Ian

Thanks for that and if my understanding is correct TCA’s still block reuptake receptors and by the same mechanism, albeit they also block noradrenalin as well as serotonin. So am I right in thinking that they still possess the same activation effects as SSRI’s.

The literature says that they have more SideFX and more drop outs than SSRI’s and it’s this that worries me...I may jump out of the frying pan into the fire !!!

But I guess that’s the only route left, as I’ve tried many SRI medications and my body just rejects everyone of them and doesn’t give me my life back...I’m gonna have to bite the bullet soon, so after reading my history which TCA would you go for (Putting yourself in my shoes, if that’s possible)

I’m thinking the TCA’s more geared towards 5ht would be better for me, as I’ve responded to SRI meds in the past and the cream of the crop is imipramine and clomipramine with the latter ki being around 0.4 for 5ht and imipramine 1.4 for 5ht

So I’ve narrowed it down to these two meds and because my mum did so well on imipramine, I’m leaning towards that....Your thoughts please ??? Ta John

[panic_down_under]

Thanks for that and if my understanding is correct TCA’s still block reuptake receptors and by the same mechanism, albeit they also block noradrenalin as well as serotonin. So am I right in thinking that they still possess the same activation effects as SSRI’s.

Imipramine and especially clomipramine may do as they bind to serotonin transporters as strongly as the most potent SSRIs. But in practice this doesn't seem to be an issue. I can't tolerate SSRIs, they make me manic even at low doses. Yet I took imipramine at or above the absolute maximum recommended dose for years without mania creeping in.


The literature says that they have more SideFX and more drop outs than SSRI’s and it’s this that worries me...I may jump out of the frying pan into the fire !!!

They generally produce less severe initial side-effects, but may have more ongoing ones such as dry mouth and constipation. Also consider that TCAs haven't been the first choice ADs for about 30 years. SSRIs are almost always prescribed first with TCAs only being considered if they and SNRIs fail so much of the TCA data comes from the more difficult cases which can provide a distorted picture. Plus, what is the point of taking an AD which doesn't work just because it has fewer side-effects? You might as well take M&Ms instead.


so after reading my history which TCA would you go for (Putting yourself in my shoes, if that’s possible)

...I’ve narrowed it down to these two meds and because my mum did so well on imipramine, I’m leaning towards that....Your thoughts please ???

Either imipramine or amitriptyline with a bias toward imipramine as it binds less strongly to histamine HI and muscarinic acetylcholine receptors so dry mouth, constipation and sedation should be less of an issue, although, as with everything AD, YMMV. If either works, but falls short of full effectiveness you can always switch to the more potent clomipramine later. Alternately, if the serotonergic side-effects are too severe a switch to amitriptyline will probably resolve them.

[SideFX]

Imipramine and especially clomipramine may do as they bind to serotonin transporters as strongly as the most potent SSRIs. But in practice this doesn't seem to be an issue. I can't tolerate SSRIs, they make me manic even at low doses. Yet I took imipramine at or above the absolute maximum recommended dose for years without mania creeping in.



They generally produce less severe initial side-effects, but may have more ongoing ones such as dry mouth and constipation. Also consider that TCAs haven't been the first choice ADs for about 30 years. SSRIs are almost always prescribed first with TCAs only being considered if they and SNRIs fail so much of the TCA data comes from the more difficult cases which can provide a distorted picture. Plus, what is the point of taking an AD which doesn't work just because it has fewer side-effects? You might as well take M&Ms instead.



Either imipramine or amitriptyline with a bias toward imipramine as it binds less strongly to histamine HI and muscarinic acetylcholine receptors so dry mouth, constipation and sedation should be less of an issue, although, as with everything AD, YMMV. If either works, but falls short of full effectiveness you can always switch to the more potent clomipramine later. Alternately, if the serotonergic side-effects are too severe a switch to amitriptyline will probably resolve them.

Thanks Ian

That is so much appreciated and you make some very good points, particularly if my AD is not lifting me completely out of depression and anxiety, then why am I continuing to tolerate it and it’s SideFX. I don’t know why, but I would say the fear of change right now !!!!

Good to hear that SSRI’s also make you climb the walls, yet TCA’s which also act on serotonin don’t trigger the same reaction...I’ve read so many people struggle with them too and yet tolerate TCA’s no problem, I hope that’s me and when the times right I will find remission through a change in meds.

Why on earth haven’t the doctors picked up on this by now and put me on a TCA - after two hospitalisations they must be ignorant or scared of the dangers in OD’s maybe.

Thanks Ian and if you don’t mind when I am ready to make the switch could I post here for support, as any med changes brings its own risks and anxiety

Thank you John

[panic_down_under]

Why on earth haven’t the doctors picked up on this by now and put me on a TCA - after two hospitalisations they must be ignorant or scared of the dangers in OD’s maybe.

A combination of ignorance and fear of the unknown. Many doctors these days have never prescribed anything but a SSRI, or SNRI. I'm going through this atm interviewing doctors near where I'm having a new house built and hoping to find an old timer who began practising before SSRIs became available in the late 1980s. Most of the younger ones have never heard of dosulepin and become very uneasy after I tell them what dose I'm on once they've read up on it. Unfortunately, my usual tactic of sounding out the local pharmacist hasn't work because there isn't another patient in the area on any TCA.

The OD concerns are mostly unfounded. Few do so on the AD they are taking and the ones that do usually survive relatively unharmed.


Thanks Ian and if you don’t mind when I am ready to make the switch could I post here for support, as any med changes brings its own risks and anxiety

That's what NMP is for, John. I'll be around provided the proverbial bus doesn't have other ideas.

take care,

Ian

[SideFX]

A combination of ignorance and fear of the unknown. Many doctors these days have never prescribed anything but a SSRI, or SNRI. I'm going through this atm interviewing doctors near where I'm having a new house built and hoping to find an old timer who began practising before SSRIs became available in the late 1980s. Most of the younger ones have never heard of dosulepin and become very uneasy after I tell them what dose I'm on once they've read up on it. Unfortunately, my usual tactic of sounding out the local pharmacist hasn't work because there isn't another patient in the area on any TCA.

The OD concerns are mostly unfounded. Few do so on the AD they are taking and the ones that do usually survive relatively unharmed.



That's what NMP is for, John. I'll be around provided the proverbial bus doesn't have other ideas.

take care,

Ian

Hi Ian

Many many thanks for the insight and information you have provided, I will use it all wisely and try to manage and mitigate the risks as much as possible, when I’m in a position to pull that trigger.

I think I will start with imipramine and see what happens fingers crossed I’ll get my full life back !!!

Thank you again John