Mirtazapine (Remeron) lowers cortisol and prolactin in normal subjects

[nandi12]

I posted this at my home board (cuttingedgemuscle) but since prolactin is such a popular topic here I thought I would repost here at Elite.

This might be an alternative to Cytadren for those interested in lowering cortisol levels. It also lowers prolactin, which may be of interest to those who believe elevated prolactin contributes to gyno during AAS use (despite a lack of any evidence for this). And you get an antidepressant effect as well. Kind of like Prozac, Cytadren and bromocriptine all rolled into one, without the sexual dysfunction associated with SSRI's like Prozac, or the testosterone lowering effect of Cytadren.

Prog Neuropsychopharmacol Biol Psychiatry 2002 Dec;26(7-8):1253-61

Endocrinological effects of mirtazapine in healthy volunteers.

Schule C, Baghai T, Bidlingmaier M, Strasburger C, Laakmann G.

Psychiatric Hospital, University of Munich, Munich, Germany. [email protected]

OBJECTIVE: Unlike other antidepressants, mirtazapine does not inhibit the reuptake of norepinephrine or serotonin (5-HT) but acts as an antagonist at presynaptic alpha2-receptors and at postsynaptic 5-HT2, 5-HT3 and histamine H1-receptors. In the present investigation, the influence of acute oral administration of 15-mg mirtazapine on the cortisol (COR), adrenocorticotropin (ACTH), growth hormone (GH) and prolactin (PRL) secretion was examined in 12 healthy male subjects, compared to placebo. METHODS: After insertion of an intravenous catheter, both the mean arterial blood pressure (MAP) and the heart rate were recorded and blood samples were drawn 1 h prior to the administration of mirtazapine or placebo (7:00 a.m.), at time of administration (8:00 a.m.) and during 5 h thereafter in periods of 30 min. Concentrations of COR, ACTH, GH and PRL were measured in each blood sample by double antibody radioimmunoassay and chemiluminescence immunoassay methods. The area under the curve (AUC; 0-300 min after mirtazapine or placebo administration) was used as parameter for the COR, ACTH, GH and PRL response. Furthermore, the urinary free cortisol excretion (UFC) was determined beginning at 8:00 a.m. (time of administration of placebo or mirtazapine) up to 8:00 a.m. the day after. RESULTS: Two-sided t-tests for paired samples revealed significantly lower COR AUC, ACTH AUC, UFC and PRL AUC values after 15-mg mirtazapine compared to placebo , whereas no significant differences were found with respect to GH AUC, MAP and heart rate. CONCLUSIONS: Since the acute inhibition of COR secretion in the healthy volunteers was paralleled by a simultaneous decrease of ACTH release, central mechanisms (e.g., inhibition of hypothalamic corticotropin releasing hormone (CRH) output) are suggested to be responsible for the inhibitory effects of mirtazapine on COR secretion. Our results are of particular interest in the light of the hypercortisolism observed in depressed patients and new pharmacological approaches such as CRH1 receptor antagonists.



http://www.cuttingedgemuscle.com/Forum/showthread.php?threadid=2007

 

[THEEGAME2544]

Could be worth looking into! I'm currently popping 3000 mg of Vitamin C before workout to lower cortisol levels a little bit.

 

[The Terminator]

I took this drug one time and it knocked me on my ass, I would think any benefit from it would be outweighed by its sedative producing effect.

 

[nandi12]

It's pretty well tolerated in most people. The anxiolytic effect you describe, Terminator, makes it useful in aiding sleep in depressed patients, who often sleep poorly. It is kind of like ketotifen in that regard. It also seems to stimulate the appetite, much like ketotifen. It might not be the drug for everyone, but I sleep poorly and often have to resort to benzodiazepines for sleep. This might be an anabolic alternative for people who are taking other antidepressants such as Prozac or Zoloft.


Hum Psychopharmacol 2002 Jun;17 Suppl 1:S37-41

Tolerability and safety aspects of mirtazapine.

Nutt DJ.

University of Bristol, Bristol, UK.

The tolerability and safety profile of the noradrenergic and specific serotonergic antidepressant (NaSSA) mirtazapine reflects its unique pharmacological profile. The 5-HT(2) blocking effect contributes towards its anxiolytic effects and benefits on sleep, as well as preventing the sexual dysfunction that may occur with non-specific stimulation of the serotonin system by drugs such as the selective serotonin reuptake inhibitors (SSRIs). In addition, 5-HT(3) blockade by mirtazapine helps to prevent nausea and vomiting. Weight gain is the most commonly reported side-effect of mirtazapine, although there is evidence to suggest that this is not a significant problem during long-term treatment. In conclusion, mirtazapine has a good tolerability and safety profile that demonstrates several benefits over other antidepressants. Copyright 2002 John Wiley & Sons, Ltd.

 

[SCOTTY-TWO-HOTTY]

This is an interesting drug... for me especially. I have a sleep disorder... I have trouble getting to sleep and staying asleep. It is almost surely caused by anxiety. I've been on a low-dose tricyclic antidepressant(25mg/Amitriptyline)for 4 years to help me with this. I started taking Paxil in November(20mg/ED)and I've only had to take Amitriptyline once or twice a week since then, as Paxil has helped my sleep considerably.

I'd like to use Mirtazapine in place of Paxil... it sounds promising and would be more condusive to my bodybuilding lifestyle. Does anyone have any info/experience with respect to Mirtazapine's anti-anxiety qualities... if it has any.

 

[nandi12]

I have not yet personally tried it Scotty. I'm going to talk to my doc next week. It has been used successfully to treat the anxiety associated with social phobias, as well as the anxiety that very often accompanies depression.

There is a trend in medicine now to treat sleep problems with antidepressants first, rather than resorting to benzodiazepines.

Here is an abstract that might help.


CNS Drug Rev 2001 Fall;7(3):249-64

A review of the pharmacological and clinical profile of mirtazapine.

Anttila SA, Leinonen EV.

Department of Psychogeriatrics, Tampere University Hospital, FIN-33380 Pitkaniemi, Finland. [email protected]

The novel antidepressant mirtazapine has a dual mode of action. It is a noradrenergic and specific serotonergic antidepressant (NaSSA) that acts by antagonizing the adrenergic alpha2-autoreceptors and alpha2-heteroreceptors as well as by blocking 5-HT2 and 5-HT3 receptors. It enhances, therefore, the release of norepinephrine and 5-HT1A-mediated serotonergic transmission. This dual mode of action may conceivably be responsible for mirtazapine's rapid onset of action. Mirtazapine is extensively metabolized in the liver. The cytochrome (CYP) P450 isoenzymes CYP1A2, CYP2D6, and CYP3A4 are mainly responsible for its metabolism. Using once daily dosing, steady-state concentrations are reached after 4 days in adults and 6 days in the elderly. In vitro studies suggest that mirtazapine is unlikely to cause clinically significant drug-drug interactions. Dry mouth, sedation, and increases in appetite and body weight are the most common adverse effects. In contrast to selective serotonin reuptake inhibitors (SSRIs), mirtazapine has no sexual side effects. The antidepressant efficacy of mirtazapine was established in several placebo-controlled trials. In major depression, its efficacy is comparable to that of amitriptyline, clomipramine, doxepin, fluoxetine, paroxetine, citalopram, or venlafaxine. Mirtazapine also appears to be useful in patients suffering from depression comorbid with anxiety symptoms and sleep disturbance. It seems to be safe and effective during long-term use.


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[SCOTTY-TWO-HOTTY]

With respect to Mirtazapine's ability to lower Cortisol... is its action the same as Cytadren? I ask this because daily administration of Cytadren, by a person with normal Cortisol levels, would render the drug useless. The following is quoted from W.Llewellyn: "After a short period of regular use, your body will react to lowered Cortisol levels and release increased amounts of another hormone, ACTH(adrenocorticotropic hormone), in response. Increased ACTH will overcome the activity of Cytadren, resulting in your body resuming normal Cortisol production, making the drug useless."

Would daily administration of Mirtazapine have similar results?

I can't find(Remeron)Mirtazapine in the CPS... how long has it been available for prescription? Does anyone know the price of this drug... in relation to the price of Paxil? I pay $2 CDN/20mg tab.

 

[DangerousGrounds]

I took the 30mg ones that are chew-able and orals. They did make me sleep great but I did not have no drive or ambitions. I felt like a zombie 24/7.
It is also supposed to increase apatite but I don't like it I took it for about a month straight and the side effects still did not go away.
Its not for me maybe others it may be suited for better I hate Remeron tabs personally.

 

[nandi12]

With respect to Mirtazapine's ability to lower Cortisol... is its action the same as Cytadren?

The two drugs are thought to work via different mechanisms. Cytadren is believed to block the production of cortisol in the adrenal glands by interrupting the steroidogenic pathway. This is responsible for the decrease in testosterone production as well. However, there is evidence that Cytadren blocks ACTH secretion as well, so Bill Llewellyn may not be correct in his assertion. See abstract below.

Mirtazapine on the other hand definitely blocks ACTH production so the feedback increase in cortisol will not occur. To quote from the first abstract I posted:

"Since the acute inhibition of COR secretion in the healthy volunteers was paralleled by a simultaneous decrease of ACTH release, central mechanisms (e.g., inhibition of hypothalamic corticotropin releasing hormone (CRH) output) are suggested to be responsible for the inhibitory effects of mirtazapine on COR secretion."




Pol Tyg Lek 1992 Nov 2-9;47(44-45):1006-8

[Effect of aminoglutethimide on ACTH plasma levels in Cushing's disease and Nelson syndrome]

[Article in Polish]

Kasperlik-Zaluska AA, Migdalska B, Jeske W, Niegowska E, Wisniewska-Wozniak T.

Kliniki Endokrynologii CMKP w Warszawie.

Out of all steroidogenesis inhibitors aminoglutethimide is most frequently used agent for so-called chemical adrenalectomy, especially in oncological cases. The present studies aimed at assessing an effect of the inhibition of cortisol synthesis on plasma ACTH in patients treated with aminoglutethimide. According to the rules of negative feedback, an increase in plasma ACTH should be expected. Aminoglutethimide has been administered to 24 patients with Cushing's disease for 1-6 months. Plasma ACTH did not increase but statistically significantly decreased despite a decrease in blood cortisol. It indicates that aminoglutethimide directly inhibits ACTH secretion. . No return of the normal circadian rhythm of cortisol and ACTH release suggests that the drug exerts an effect on ACTH release regulating mechanisms. No definite results were achieved in patients with Nelson syndrome treated with aminoglutethimide for a short period of time. Plasma ACTH levels tend to decrease but no statistical significance was observed in comparison with placebo. It may depend on markedly increased corticotrophin secretion in Nelson tumors.\


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[SCOTTY-TWO-HOTTY]

Thanks nandi... Karma to you. Great thread Bro.

Dangerous Grounds- What did you pay for that drug? Was it prescribed to you by a Doctor?