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Thread: Trazodone 5HT2a theory

  1. #1
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    Default Could low-dose Trazodone help flushing?

    Hey everyone,

    I understand the generally accepted theory is antagonising 5ht2a is helpful for controlling flushing, hence one of the reasons for the popularity of low-dose Mirtazapine.

    Trazadone is a 5ht2 antagonist, and similarly to Mirtazapine, has different properties at varying doses.

    At 25mg and below, Trazodone is said to act purely as a 5ht2a antagonist, avoiding any adrenergic activity.

    A possible theoretical benefit of low-dose Trazadone over Mirtazapine; it would be Ďcleanerí, i.e. avoiding activity at 5ht2c and H1. This may or may not be desirable depending on your personal circumstances. One possible advantage could be less of the weight gain side-effect. (On the contrary, Trazadoneís metabolite acts as a 5ht2c agonist, resulting in satiation.)

    In the UK the lowest available dose is 50mg capsules, which isnít low enough. Seems like thereís a liquid version at 50mg per 5ml which would allow for low dosing. In other countries it might be available in tablet form which can be easily broken up.

    Of course Iíve no idea if this will be helpful for flushing, its just theory.

    Any thoughts on this?

    https://www.researchgate.net/publica...tate_carcinoma

    http://citeseerx.ist.psu.edu/viewdoc...=rep1&type=pdf
    Last edited by Brooks; 15th February 2019 at 11:58 AM.

  2. #2
    Senior Member Brady Barrows's Avatar
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    You are bringing up some deep stuff here. I had to Wikipedia just about everything you wrote and try to wrap my head around what you are discussing. The nutshell conclusion I offer is asking you first, why don't you like Mirtazapine? It has been listed a long time as an anti flushing drug and is included with the list of prescription and non prescription drugs to avoid flushing.

    If you don't like Mirtazapine because of its side effects, there are similar if not other side effects taking Trazadone. The list is extensive, especially discussing priapism.

    Your theory of it being 'cleaner' i.e., 'avoiding activity at 5ht2c and H1' or less of a weight gain points to a concern over side effects which may answer my second question. However, a cursory review of Trazadone says, "The combined actions of 5-HT2A and 5HT2C receptor antagonism with serotonin reuptake inhibition only occur at moderate to high doses of trazodone" so do you really think taking 25 mg would make any difference? Maybe a 'less is more' approach is what you are after? So if you have a Rx for Mirtazpine or another SSRI I would think your doctor may be tolerant of you trying a trial run with Trazadone and if you really are concerned about splitting a capsule you can get empty gel caps and simply carefully take half of the content of one Trazadone to an empty gel capsule and voila!

    As for naming this the Trazodone 5ht2a Theory which caught my eye and reeled me in (I thought you were coming up with a new cause for rosacea) and wanted to know more, it should be entitled Trazodone 5ht2a Treatment which would clear this up a bit, while understanding the 5-HT2A receptor is a daunting task that boggles the mind with G protein-coupled receptor, G protein, which are a bit overwhelming and over my head. However, this did catch my eye when giving a cursory reading of Trazadone, "Trazodone's potent α1-adrenergic blockade may cause some side effects like orthostatic hypotension and sedation."

    So are you more concerned with avoiding flushing that you are with avoiding a rosacea flareup? There is a difference.
    Brady Barrows
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  3. #3
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    I didnít get on with Mirtazapine but thankfully itís helping many of us.

    No doubt Trazodone has its side effects, but they could be minimal at very low doses. RE priapism, itís my understanding this is due to alpha 1 blockade + 5ht2c activation (from Trazodoneís metabolite), technically speaking, neither of which should occur / be appreciable at low-enough doses.

    RE less is more, yes - ďplasma trazodone concentrations after oral administration in humans,21,22,40 predict that 1 mg of trazodone will occupy about half of 5-HT2A receptors (ie, the top of the 5-HT2A bar).Ē http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.605.7477&rep=rep1&type=pdf

    Splitting the content of a capsule isnít impossible, but the liquid version would be easier to achieve low dosing such as whatís suggested above.

    The word treatment isnít included in the tittle because it hasnít been proven as such - itís just theory, the drug may / may not be helpful.

    RE hypotension, etc. yes Trazodone becomes adrenergic after a certain point as does Mirtazapine - but itís the Serotonin 2A antagonistic properties weíre after, which may be achievable exclusively at low-enough dosing (i.e. under 25mg).

    Just on the look out for anything that could potentially help us combat flushing. Many complain of weight gain, etc from Mirtazapine, I think itís worth exchanging ideas to potentially circumvent the issue or explore as potential adjunct treatments to existing protocols.
    Last edited by Brooks; 15th February 2019 at 02:58 PM.

  4. #4
    Senior Member Brady Barrows's Avatar
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    Quote Originally Posted by Brooks View Post
    I didnít get on with Mirtazapine but thankfully itís helping many of us. No doubt Trazodone has its side effects, but they could be minimal at very low doses. RE priapism, itís my understanding this is due to alpha 1 blockade + 5ht2c activation (from Trazodoneís metabolite), technically speaking, neither of which should occur / be appreciable at low-enough doses. RE less is more, yes - ďplasma trazodone concentrations after oral administration in humans,21,22,40 predict that 1 mg of trazodone will occupy about half of 5-HT2A receptors (ie, the top of the 5-HT2A bar).Ē http://citeseerx.ist.psu.edu/viewdoc...=rep1&type=pdf Splitting the content of a capsule isnít impossible, but the liquid version would be easier to achieve low dosing such as whatís suggested above. The word treatment isnít included in the tittle because it hasnít been proven as such - itís just theory, the drug may / may not be helpful. RE hypotension, etc. yes Trazodone becomes adrenergic after a certain point as does Mirtazapine - but itís the Serotonin 2A antagonistic properties weíre after, which may be achievable exclusively at low-enough dosing (i.e. under 25mg). Just on the look out for anything that could potentially help us combat flushing. Many complain of weight gain, etc from Mirtazapine, I think itís worth exchanging ideas to potentially circumvent the issue or explore as potential adjunct treatments to existing protocols.
    You are way more educated and smart about this than me. What have you got to lose? Jump in and report back your results. You didn't answer my question about you are more concerned with avoiding flushing than a rosacea flareup?
    Brady Barrows
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    Iím not sure I understand the distinction between the two in this context - my interest is in treating the flushes associated with subtype 1 Rosacea

  6. #6
    Senior Member Brady Barrows's Avatar
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    Quote Originally Posted by Brooks View Post
    Iím not sure I understand the distinction between the two in this context - my interest is in treating the flushes associated with subtype 1 Rosacea
    Did you read the article I mentioned in my earlier post? Or this post may be more helpful to understand the difference. Not all rosaceans complain of flushing. Some are simply more concerned with a rosacea flare up, which is completely different.
    Brady Barrows
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