Mirtazapine Increases T4-T3 Conversion, Possible Antidepressant Mechanism

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DaveFoster

DaveFoster

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That's amazing why so high
I'm using it along with progesterone, caffeine, aspirin, and cyproheptadine to compensate for a thyroid deficiency while I acclimate to thyroid.
 

Frankdee20

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I took Remeron to help my poor sleeping for around 3 weeks and I kid you not my breasts went from a C to almost a DD...in that small time. scared me so I stopped. I wonder if it somehow increases prolactin...it definitely increases serotonin.

It’s a shame our paths didn’t cross then
 

Shai Hulud

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Mirtazapine is an adrenergic antagonist (a2 receptors IIRC.) It can cause fibrosis of the heart, and thyroid hormone can reverse this effect. Progesterone and cyproheptadine can prevent it as well, particularly the latter. T3 doesn't always increase the heart rate. An EKG during administration is wise. A better option to try first would be cypro and progesterone if you're trying to increase T4 > T3 conversion. Pregnenolone and T3 can lower cortisol.
Do you have evidence this specific drug does cause this side effect in humans?
I'm under the impression this whole thing about enhanced adrenergic transmission was more for marketing.
A friend who is a psychopharmacologist told me affinity is too small while in his clinical experience antagonizing of autoreceptors chronically wasn't really an effective concept in the first place.
Later I asked another friend of mine who works in a psychiatric clinic. They use Mirtazapine quite often and I asked him if he had noticed a stimulatory effect in his patients at 45 mg daily, which wasn't the case.

I took it for some months at 30 and later 15 mg and it made me really drowsy for a long time, while Doxepin never did that. I would regularily get very tired in the evening around 2-3.5 hours before I'd go to bed normally and it started before I took my dose. Doxepin could make me drowsy the next day when I upped the dose, but not over the next weeks with chronic use. Adaption was way faster. So I guess this effect wasn't just from H1-antagonism.
 
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DaveFoster

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Do you have evidence this specific drug does cause this side effect in humans?
I'm under the impression this whole thing about enhanced adrenergic transmission was more for marketing.
A friend who is a psychopharmacologist told me affinity is too small while in his clinical experience antagonizing of autoreceptors chronically wasn't really an effective concept in the first place.
Later I asked another friend of mine who works in a psychiatric clinic. They use Mirtazapine quite often and I asked him if he had noticed a stimulatory effect in his patients at 45 mg daily, which wasn't the case.

I took it for some months at 30 and later 15 mg and it made me really drowsy for a long time, while Doxepin never did that. I would regularily get very tired in the evening around 2-3.5 hours before I'd go to bed normally and it started before I took my dose. Doxepin could make me drowsy the next day when I upped the dose, but not over the next weeks with chronic use. Adaption was way faster. So I guess this effect wasn't just from H1-antagonism.
It's not the hardest on the heart with regard to QT prolongation, but it's not as safe as say, bupropion.

It does cause fibrosis through agonism of the 5-HT2B receptor:

"Exposure to antidepressants was categorized by the type of antidepressant, affinity for the 5-HT transporter and individual antidepressant. The antidepressants were classified into the following 3 categories according to their affinities for the 5-HT transporter: a high-affinity group (fluoxetine, paroxetine, sertraline, and clomipramine), a moderate-affinity group (citalopram, fluvoxamine, imipramine, venlafaxine, and amitriptyline), and a low-affinity group (trazodone, bupropion, maprotiline, mirtazapine, and dothiepin)28,29 (Appendix 1)."

"We found a 1.4-fold increase in the risk of VHD among current users of antidepressants. Among current users, a dose–response effect was found in patients with cumulative DDDs [defined daily dose, indicating a higher dosage resulting in increased fibrosis.] Moreover, the users who were currently taking TCAs and antidepressants with moderate and low affinities for the 5-HT transporter were at significant higher risks of VHD [valvular heart disease]."
 
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Shai Hulud

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It's not the hardest on the heart with regard to QT prolongation, but it's not as safe as say, bupropion.

It does cause fibrosis through agonism of the 5-HT2B receptor:

"Exposure to antidepressants was categorized by the type of antidepressant, affinity for the 5-HT transporter and individual antidepressant. The antidepressants were classified into the following 3 categories according to their affinities for the 5-HT transporter: a high-affinity group (fluoxetine, paroxetine, sertraline, and clomipramine), a moderate-affinity group (citalopram, fluvoxamine, imipramine, venlafaxine, and amitriptyline), and a low-affinity group (trazodone, bupropion, maprotiline, mirtazapine, and dothiepin)28,29 (Appendix 1)."

"We found a 1.4-fold increase in the risk of VHD among current users of antidepressants. Among current users, a dose–response effect was found in patients with cumulative DDDs [defined daily dose, indicating a higher dosage resulting in increased fibrosis.] Moreover, the users who were currently taking TCAs and antidepressants with moderate and low affinities for the 5-HT transporter were at significant higher risks of VHD [valvular heart disease]."

The quote only describes affinity, not agonism. I've searched for and it seems it antagonizes 5HT2B with a Ki of 350nM (which is said to be clinically irrelevant). Don't know if valvular heart disease could be a result of both agonism and antagonism, though, especially with long-term use.
 
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DaveFoster

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The quote only describes affinity, not agonism. I've searched for and it seems it antagonizes 5HT2B with a Ki of 350nM (which is said to be clinically irrelevant). Don't know if valvular heart disease could be a result of both agonism and antagonism, though, especially with long-term use.
Dr. Peat specifically mentioned that amitriptyline and mirtazapine have been tied with occurrences of fibrosis.

I know you think that anti-serotonin drugs eventually cause problems, but you've said that amitriptyline is relatively safe. Do you think it's safer than mirtazapine for moderate-term use? I've read that mirtazapine's a "successor" to mianserin.

Dr. Peat: "Although the structure suggests that it might be safer, fibrosis has been associated with both of them, and I think it’s best to concentrate on optimizing the metabolism, with thyroid, pregnenolone, progesterone, etc."
 

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