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Thread: Imipramine or Clomipramine

  1. #41
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    Re: Imipramine or Clomipramine

    Quote Originally Posted by SideFX View Post
    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

  2. #42
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    Re: Imipramine or Clomipramine

    Quote Originally Posted by SideFX View Post
    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.
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    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. #43
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    Re: Imipramine or Clomipramine

    Quote Originally Posted by panic_down_under View Post
    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.
    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

  4. #44
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    Re: Imipramine or Clomipramine

    Quote Originally Posted by SideFX View Post
    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.
    __________________
    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.

  5. #45
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    Re: Imipramine or Clomipramine

    Quote Originally Posted by panic_down_under View Post
    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

  6. #46
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    Re: Imipramine or Clomipramine

    Quote Originally Posted by SideFX View Post
    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.
    __________________
    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. #47
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    Re: Imipramine or Clomipramine

    Quote Originally Posted by panic_down_under View Post
    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

  8. #48
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    Re: Imipramine or Clomipramine

    Quote Originally Posted by SideFX View Post
    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
    __________________
    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.

  9. #49
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    Re: Imipramine or Clomipramine

    Quote Originally Posted by panic_down_under View Post
    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

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