Mirtazapine Increases T4-T3 Conversion, Possible Antidepressant Mechanism

[DaveFoster]

Dr. Peat has written about cortisol's ability to impair the liver's conversion of T4 to T3, and since elevated serotonin signals the ACTH to produce excess cortisol, it's no surprise that an anti-serotonin drug lowers cortisol and restores the endogenous conversion of T4 to T3.

Those who have elevated free T4 (FT4) as indicated by blood tests could benefit from an anti-serotonin drug, as such would allow for proper T4 conversion in the liver, and if adequately supported could result in an amplification of the pathways that detoxify estrogen from the body, which could lower cortisol even further in the long-term.

Further, Dr. Peat (and forum member haidut) have written extensively about the involvement of cortisol in depression, so it's not surprise that a drug (mirtazapine) that happens to lower cortisol has a superior record for treating major depressive disorder, panic disorder, and other mental disorders. It's also no surprise that the patients involved in this study had greater depression (as indicated by higher HAM-D scores) when their FT4 was highest. Lower FT4 resulted in decreased symptoms of depression, so there's a direct correlation between good thyroid function and happiness.

Effect of mirtazapine on thyroid hormones in adult patients with major depression. - PubMed - NCBI

Hypothalamic pituitary thyroid (HPT) axis abnormalities and alterations in major depression are reported in the literature. The aim of our study was to evaluate the effect of mirtazapine on thyroid hormones after 6 months of therapy in a sample of adult outpatients with Major Depression (MD). 17 adult outpatients (7 men, 10 women) with MD according to DSM-IV criteria, were included in the study. All participants had to have met criteria for a major depressive episode with a score of at least 15 on the Hamilton Depression Rating Scale (HAM-D). Fasting venous blood samples were obtained for determination of serum Thyroid Stimulating Hormone (TSH), Free T3 (FT3) and Free T4 (FT4) concentrations both at baseline and after 6 months of therapy. HAM-D scores decreased significantly from the first day of treatment to the end of the treatment period (P<0.001) and twelve patients (70.6%) were classified as responders. A significant increase in FT3 concentrations was found between baseline and the end of the treatment period (P=0.015), whereas FT4 concentrations decreased (P=0.046). No significant changes were found in TSH levels. Higher FT4 concentrations at baseline predicted higher HAM-D scorers both at baseline and at the end of the treatment period. Furthermore, higher FT3 concentrations at endpoint were found to be predictors of lower HAM-D scores. Long-term treatment with mirtazapine increases FT3 levels and decreases FT4 maybe involving the deiodination process of T4 into T3.

 

[dookie]

@DaveFoster

I found that using a small dose of cyproheptadine, once, relieves a bit depression and helplessness, but if I keep using it, I get more depressed than I was before..

 

[DaveFoster]

@dookie

With the cypro, it could be terminating the stress response, which can bring relief, but you have minimal thyroid activity when the sympathetic response terminates.

Alternatively or in addition to, cyproheptadine strongly antagonizes D3, which can cause anhedonia.

 

[mujuro]

I loved mirtazapine but the asthenia was a deal breaker. Do you know if it wears off?

 

[Giraffe]

Not sure mirtazapine was causative for improved thyroid hormone levels. You can't rule out seasonal effects. (By the way, the difference was quite small.)

As for the cortisol lowering effect, there is a German doctor thesis (link) in which cortisol levels were tested before treatment, after one week and after five weeks of treatment with 45 mg mirtazapine. About half of the patients were classified as non-suppressors after DEX/CRH test. In those, cortisol was drastically lowered at week 1. It had raised again at week 5, but was still below pre-treatment levels (Tabelle 6). Different picture in the suppressors (Tabelle 5). I would like to see studies that last longer.

Dexamethasone suppression test - Wikipedia

 

[Simonsays]

This is very interesting.

Could citalopram do the same? Its a SSRI too no? I understand it initially stimulates the HPA axis then supresses it, lowering cortisol??

When i was taking citalopram earlier in the year, i had these very strange symptoms after a few weeks.

My temps shot up (noticeable my morning ones especially) and my weight started to fall off dramatically. I was worried id got some terrible illness. Or it seemed like my thyroid function was finally functioning after all these years, as the temps would indicate. I noticed my appetite also seemed suppressed.

I cant say it lifted my depression but i developed chronic insomnia, like consecutive nights without any sleep and id fall asleep during the day, that got so bad i had to stop taking it.

Since then the weights gone back on, temps dropped and T4 levels risen so much doctor telling me to lower my thyroxine.

 

[DaveFoster]

I loved mirtazapine but the asthenia was a deal breaker. Do you know if it wears off?

It seems to; so does the aggressive effect to some degree. At 3.5 mg, I don't really feel any downsides besides the sedation, which I don't mind.

I drink a lot more coffee though, so it would definitely offset the asthenia.

 

[Constatine]

This is very interesting.

Could citalopram do the same? Its a SSRI too no? I understand it initially stimulates the HPA axis then supresses it, lowering cortisol??

When i was taking citalopram earlier in the year, i had these very strange symptoms after a few weeks.

My temps shot up (noticeable my morning ones especially) and my weight started to fall off dramatically. I was worried id got some terrible illness. Or it seemed like my thyroid function was finally functioning after all these years, as the temps would indicate. I noticed my appetite also seemed suppressed.

I cant say it lifted my depression but i developed chronic insomnia, like consecutive nights without any sleep and id fall asleep during the day, that got so bad i had to stop taking it.

Since then the weights gone back on, temps dropped and T4 levels risen so much doctor telling me to lower my thyroxine.

Weight loss and very high Temps are actually a sign of elevated serotonin. Especially if your appetite was decreased.

 

[Simonsays]

Thanks @Constatine , so it wasnt a thyroid boost, just elevated serotonin.

 

[bionicheart]

@DaveFoster I read T3 does the following on wiki: "T3 increases the heart rate and force of contraction, thus increasing cardiac output, by increasing β-adrenergic receptor levels in myocardium.[10] This results in increased systolic blood pressure and decreased diastolic blood pressure." so my question is, if Mirtazapine increases T3 is it beneficial in improving the heart function of people with a predisposition to dilated congestive heart failure..? Or could it make problems worse with the increased heart rate? Thanks

 

[DaveFoster]

@DaveFoster I read T3 does the following on wiki: "T3 increases the heart rate and force of contraction, thus increasing cardiac output, by increasing β-adrenergic receptor levels in myocardium.[10] This results in increased systolic blood pressure and decreased diastolic blood pressure." so my question is, if Mirtazapine increases T3 is it beneficial in improving the heart function of people with a predisposition to dilated congestive heart failure..? Or could it make problems worse with the increased heart rate? Thanks

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.

 

[hiconscience]

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.

 

[bionicheart]

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.

What symptoms were you having to indicate it increases serotonin? I've been on it for a week now and it's alleviated all of my GI issues, except it's a little constipating. I have been more aggressive/moody but I'm hoping that will go away in time...

 

[CoconutEffect]

I've been on it for over a month.
The jaundice scare dissipated when I got to the ER, got bloods the following morning and lipase was ~ 3x normal at 150, normal bilirubin.
We kept the mirtazapine and tested Lipase a few days later and it was in the normal range.

Yellowing is gone, but that may be because no one is around to see it HA! ... because the girlfriend is gone too. I became hyper focused on my business, and a bit ornery (manic switch?)

Maybe, but
I sleep when I want to now. I'm more productive during the days, more industrious, but that could be the consequence of not wasting time at night trying to sleep.

Waking is still extremely difficult, I wake up in despair.
It hasn't had any effect, for better or for worse, on my mornings. No side effects. 7.5 mg at night, if that doesn't do the trick (usually if I had taken stimulants that day, which I often need to wake up) another 7.5 mg an hour later will do.

Anyone trying the so called "activating higher doses" 30-45mg?
While also using it for sleep at night?
If I wanted the sleep benefits and maybe some antidepressant benefit, would it look like 7.5 mg at night and 37.5 mg in the morning?

I see my psychiatrist 7.5

Interesting medication. I'm bipolar 2.

 

[Simonsays]

Ive been on it a few weeks (15mg) and i think its having an effect slightly mentally and another not unpleasant side effect sems to be very vivid dreams, like im tripping out, definietly not nightmares.

 

[CoconutEffect]

Ive been on it a few weeks (15mg) and i think its having an effect slightly mentally and another not unpleasant side effect sems to be very vivid dreams, like im tripping out, definietly not nightmares.

what kind of mental effect

 

[Simonsays]

positive

 

[DaveFoster]

I've been on it for over a month.
The jaundice scare dissipated when I got to the ER, got bloods the following morning and lipase was ~ 3x normal at 150, normal bilirubin.
We kept the mirtazapine and tested Lipase a few days later and it was in the normal range.

Yellowing is gone, but that may be because no one is around to see it HA! ... because the girlfriend is gone too. I became hyper focused on my business, and a bit ornery (manic switch?)

Maybe, but
I sleep when I want to now. I'm more productive during the days, more industrious, but that could be the consequence of not wasting time at night trying to sleep.

Waking is still extremely difficult, I wake up in despair.
It hasn't had any effect, for better or for worse, on my mornings. No side effects. 7.5 mg at night, if that doesn't do the trick (usually if I had taken stimulants that day, which I often need to wake up) another 7.5 mg an hour later will do.

Anyone trying the so called "activating higher doses" 30-45mg?
While also using it for sleep at night?
If I wanted the sleep benefits and maybe some antidepressant benefit, would it look like 7.5 mg at night and 37.5 mg in the morning?

I see my psychiatrist 7.5

Interesting medication. I'm bipolar 2.

I've been having success taking pregnenolone in the morning. 500 mg pregnenolone daily treats bipolar disorder.

Pregnenolone Treats Bipolar Disorder

I'm adding some pages at the moment on bipolar disorder and possible therapies.

 

[Frankdee20]

That's a ridiculous amount of Pregnenalone. I'd feel safer injecting Cocaine than using that high a dose.

 

[DaveFoster]

That's a ridiculous amount of Pregnenalone. I'd feel safer injecting Cocaine than using that high a dose.

I've been taking 5 grams of pregnenolone daily for a couple weeks: no side effects whatsoever.