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  1. #1

    Imipramine or Clomipramine

    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 couldnít 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 SNRIís. 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 Iím extremely close too...So anyway Iíve 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. Iím currently on:

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

    I am suffering everyday, but I have focus to work, albeit Iím 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 Iíve done a lot of research on meds and self help and god knows Iím trying to carry on and put my life back together, but these meds just ainít doing it for me. Now to the point, my mum was originally on an MAOI, then got took off that in the 80ís 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 Iíve wondered if Imipramine might be good for me.

    But Iím so frightened of going through more med switching and donít want to lose everything Iíve 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 canít suffer or tolerate how I am...I need help and the doctors are lost and they will go with whatever I want (Exept MOAIís)

    Any nuggets of wisdom would be soooo much appreciated please I know I wonít be able to carry on too much longer !! Thank you

  2. #2
    Join Date
    Jan 2017
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    Re: Imipramine or Clomipramine

    Quote Originally Posted by SideFX View Post
    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, 2016 and Amsterdam JD, 2009, found the likelihood of antidepressants working after each restart drops by between 19-25% (see also: Bosman RC, 2018; Amsterdam JD, 2009; Leykin Y, 2007; Paholpak S, 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 couldnít 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, 2014; Nochi R, 2013; --Sun Y, 2013; Song J, 2012; Wu X, 2009; Stefovska VG, 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.

    Iím currently on:

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

    I am suffering everyday, but I have focus to work, albeit Iím 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 80ís 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 Iíve 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 Iím so frightened of going through more med switching and donít want to lose everything Iíve 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 MOAIís)
    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).
    __________________
    .

    - - What to know about: Telepsychiatry | Teletherapy - -




    The opinions expressed above are based on my observations and, where applicable, interpretation of cited data and are general in nature. Consult your physician before acting on anything stated.

  3. #3

    Re: Imipramine or Clomipramine

    Quote Originally Posted by panic_down_under View Post
    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, 2016 and Amsterdam JD, 2009, found the likelihood of antidepressants working after each restart drops by between 19-25% (see also: Bosman RC, 2018; Amsterdam JD, 2009; Leykin Y, 2007; Paholpak S, 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, 2014; Nochi R, 2013; --Sun Y, 2013; Song J, 2012; Wu X, 2009; Stefovska VG, 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

  4. #4
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    Re: Imipramine or Clomipramine

    Quote Originally Posted by SideFX View Post
    I hope you donít 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.

  5. #5

    Re: Imipramine or Clomipramine

    Quote Originally Posted by panic_down_under View Post
    Sure. This is what the forum is for.
    Thanks Ian

    One thing I donít understand is how the mechanism of action differs between SSRIís and TCAís 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 SSRIís and Iím familiar with Ken Gillmanís 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

  6. #6
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    Re: Imipramine or Clomipramine

    Quote Originally Posted by SideFX View Post
    One thing I donít understand is how the mechanism of action differs between SSRIís and TCAís 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 SSRIís
    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) 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 the same process as ADs, neurogenesis.
    __________________
    .

    - - What to know about: Telepsychiatry | Teletherapy - -




    The opinions expressed above are based on my observations and, where applicable, interpretation of cited data and are general in nature. Consult your physician before acting on anything stated.

  7. #7
    Join Date
    Feb 2016
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    1,657

    Re: Imipramine or Clomipramine

    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.
    __________________
    If you are one of the lucky souls allowed to enter NZ at this time please remember two things:

    1. We did the hard months in lockdown abiding by rules for you to get here.
    2. No one gives a shit if you prefer white towels or hotels with sea views.
    You're in quarantine for fourteen days ...obey the rules.

  8. #8

    Re: Imipramine or Clomipramine

    Quote Originally Posted by panic_down_under View Post
    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) 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 the same process as ADs, neurogenesis.
    Again thank you Ian

    I didnít 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 SSRIís give me and Iíve never properly tried a therapeutic dose of a TCA for a reasonable time.

    I donít 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 donít know why the Pdocs havenít tried it...Iíve told him many times (They seem to be so passive) and state itís not all about meds you know...Hey tell me something I donít know, but when your fighting against your meds, thereís something wrong.

    Also because Iím 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...Iíve read some previous posts. How did you find it and what condition(s) was it prescribed for ???? Many Thanks

  9. #9

    Re: Imipramine or Clomipramine

    Quote Originally Posted by WiseMonkey View Post
    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 Iím not alone with SSRIís 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 TCAís

    Thanks and can I ask which was the worst component of your illness ĎAnxietyí or ĎDepressioní ???? Thank you John

  10. #10
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    Re: Imipramine or Clomipramine

    Quote Originally Posted by SideFX View 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
    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
    Last edited by WiseMonkey; 07-07-20 at 23:37.
    __________________
    If you are one of the lucky souls allowed to enter NZ at this time please remember two things:

    1. We did the hard months in lockdown abiding by rules for you to get here.
    2. No one gives a shit if you prefer white towels or hotels with sea views.
    You're in quarantine for fourteen days ...obey the rules.

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