Mirtazapine Powerfully Lowers Cortisol

DaveFoster

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Forum member haidut has posted many studies that anti-serotonin drugs lower cortisol, and here's some more evidence that the antidepressant mirtazapine dose the same. Mirtazapine has mixed serotenergic properties, but Ray thinks it might be useful in some situations.

It's anti-serotonin and anti-cortisol effects clarifies its benefits in autism-spectrum disorders (ASD) and major depressive disorder (MDP), as well as some treatments for generalized anxiety disorders (GAD) and obsessive-compulsive disorder (OCD).

Haidut has already outlined the role of cortisol in depression:
Depression May Be Caused By Estrogen In Females And Cortisol In Males

Effects of mirtazapine on growth hormone, prolactin, and cortisol secretion in healthy male subjects. - PubMed - NCBI

"In the present study the effects of acute PO-administration of 15 mg mirtazapine on the growth hormone (GH), prolactin (PRL), and cortisol (COR) secretion were examined in eight physically and mentally healthy male subjects, compared to placebo. Mirtazapine is a new antidepressant agent which does not inhibit the reuptake of norepinephrine or serotonin but is an antagonist of presynaptic and, presumably, postsynaptic alpha 2-receptors as well as an antagonist of postsynaptic 5-HT2 and 5-HT3-receptors. After insertion of an i.v. catheter, blood samples were drawn 1 h prior to the administration of mirtazapine or placebo, at time of application, and during the time of 4 h after application in periods of 30 min. Plasma concentrations of GH, PRL, and COR were determined in each blood sample by double antibody RIA methods. The area under the curve (AUC) value was used as parameter for the GH, PRL, and COR response. With respect to GH and PRL secretion, mirtazapine did not show any effects in comparison with placebo. However, in all subjects, the COR concentrations were remarkably lower after mirtazapine compared to placebo, the difference being obvious in the mean value graphs 60 min after the application up to the end of the measurement period. The t-test for paired samples revealed a highly significant difference (P < 0.01) in COR-AUC-values between the mirtazapine group (mean COR-AUC: 1558.07 micrograms/100 ml x 240 min) and the placebo group (mean COR-AUC: 2698.86 micrograms/100 ml x 240 min). Further studies have to elucidate the question whether the demonstrated inhibition of COR secretion after application of 15 mg mirtazapine is caused by central or peripheral effects of this substance."

Ray has also spoken of the ability of the SSRI's to stimulate the adrenals to secrete cortisol, and he has endorsed a rapid tapering off of these drugs probably for that reason. Unlike venlafaxine (Effexor), mirtazapine (Remeron) lowers cortisol and can be safely tapered off very slowly without any fear of further physiological damage.

Antidepressant treatment with mirtazapine, but not venlafaxine, lowers cortisol concentrations in saliva: a randomised open trial. - PubMed - NCBI

"Lowering the concentrations of free cortisol in depressed patients may be an important prerequisite to prevent glucocorticoid-related sequelae of depression. We tested the hypothesis that the hypothalamus-pituitary-adrenal (HPA) system-dampening effects of venlafaxine and mirtazapine differ. We compared the course of morning (08.00h) and afternoon saliva cortisol (16.00h) in 42 mirtazapine- and 45 venlafaxine-treated depressed patients during a 1-week wash-out and a 4-week treatment period in a randomised open trial. Mirtazapine lowered afternoon cortisol from week 1 to 4. In contrast, during the course of the entire treatment period, venlafaxine did not attenuate saliva cortisol concentrations. Treatment effects of mirtazapine on cortisol concentrations did not differ in remitters and non-remitters to treatment. High baseline cortisol concentrations, on the other hand, were related to an unfavourable course during venlafaxine treatment and patients remitting during venlafaxine treatment had significantly lower afternoon cortisol concentrations in saliva, when compared to non-remitting patients. Thus, mirtazapine and venlafaxine show different effects on HPA system activity as measured by saliva cortisol. This may be of relevance with regard to physical sequelae of depression."

Mirtazapine is often used as an adjunct to other antidepressants, and the association of high cortisol and unsucessful use of venlafaxine point to the necessity of opposing brain serotonin as well as cortisol. As a further hypothesis, unsuccessful "relapses" from antidepressant treatment remain common, and the cause could be caused by a lacking restoration of neuronal metabolism by certain antidepressants.

Efficacy and safety of add on low-dose mirtazapine in depression

Objectives:
Although antidepressant medications are effective, they have a delayed onset of effect. Mirtazapine, an atypical antidepressant is an important option for add-on therapy in major depression. There is insufficient data on mirtazapine in Indian population; hence this study was designed to study the add-on effect of low-dose mirtazapine with selective serotonin reuptake inhibitors (SSRIs) in major depressive disorder (MDD) in Indian population.

Materials and Methods:
In an open, randomized study, 60 patients were divided into two groups. In Group A (n=30) patients received conventional SSRIs for 6 weeks. In Group B (n=30) patients received conventional SSRIs with low-dose mirtazapine for 6 weeks. Patients were evaluated at baseline and then at 1, 2, 3, 4, 5, and 6 weeks.

Results:
There was significant improvement in Hamilton Depression Rating Scale (HDRS), Montgomery and Asberg depression rating scale (MADRS) scores (P<0.05) in both groups. Mirtazapine in low dose as add on therapy showed improvement in scores, had earlier onset of action, and more number of responders and remitters as compared to conventional treatment (P<0.05). No serious adverse event was reported in either of the groups.

Conclusion:
Low-dose mirtazapine as add-on therapy has shown better efficacy, earlier onset of action and more number of responders and remitters as compared to conventional treatment in MDD in Indian patient

Mitochondrial dysfunction, oxidative stress, and major depressive disorder

"There is controversy about depression being a physical illness, in part because a reproducible, sensitive, and specific biologic marker is not available. However, there is evidence that mitochondrial dysfunction and oxidative stress may be associated with abnormal brain function and mood disorders, such as depression. This paper reviews selected human and animal studies providing evidence that intracellular mitochondrial metabolic dysfunction in specific brain regions is associated with major depressive disorder. This supports the hypothesis that chronic mitochondrial dysfunction in specific tissues may be associated with depression. Evaluation of mitochondrial dysfunction in specific tissues may broaden the perspective of depression beyond theories about neurotransmitters or receptor sites, and may explain the persistent signs and symptoms of depression."

Influence of mirtazapine on salivary cortisol in depressed patients. - PubMed - NCBI

"Unlike other antidepressants, mirtazapine does not inhibit the reuptake of norepinephrine or serotonin but acts as an antagonist at presynaptic alpha(2)-receptors, at postsynaptic 5-HT2 and 5-HT3 receptors, and at histaminergic H1 receptors. Furthermore, mirtazapine has been shown to acutely inhibit cortisol secretion in healthy subjects. In the present study, the impact of mirtazapine treatment on salivary cortisol secretion was investigated in 12 patients (4 men, 8 women) suffering from major depression according to DSM-IV criteria. Patients were treated with mirtazapine for 3 weeks, receiving 15 mg mirtazapine on day 0, 30 mg on day 1 and 45 mg per day from day 2 up to the end of the study (day 21). Response to mirtazapine treatment was defined by a reduction of at least 50% in the Hamilton Rating Scale for Depression after 3 weeks of therapy. Salivary cortisol concentrations were measured before treatment (day -1), at the beginning of treatment (day 0), after 1 week (day 7) and after 3 weeks (day 21) of treatment with mirtazapine. Saliva samples were collected hourly from 08.00 until 20.00 h. The area under the curve values served as parameter for the salivary cortisol secretion. Following analysis of variance with a repeated measures design, tests with contrasts revealed a significant reduction of cortisol concentrations already after 1 day of mirtazapine treatment that was comparable in responders and nonresponders. In addition to new pharmacological approaches such as CRH1 receptor antagonists, mirtazapine therefore appears to be an effective strategy to decrease hypercortisolism and restore HPA system dysregulation in depression. However, the importance of the acute inhibitory effects of mirtazapine on cortisol secretion for its antidepressant efficacy has to be further clarified."

Here's a follow-up to the previous study, which shows that mirtazapine tones down the pituitary to produce less ACTH and thus cortisol. Similar to cyproheptadine, mirtazapine should be able to counteract the effects of caffeine, and maybe even more effectively since mirtazapine lowers adrenaline more powerfully.

Endocrinological effects of mirtazapine in healthy volunteers. - PubMed - NCBI

"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."

Influence of mirtazapine on urinary free cortisol excretion in depressed patients. - PubMed - NCBI

"Mirtazapine has been shown to acutely inhibit cortisol secretion in healthy subjects. In the present study, the impact of mirtazapine treatment on urinary free cortisol (UFC) excretion was investigated in depression. Twenty patients (six men, 14 women) suffering from major depression according to DSM-IV criteria were treated with mirtazapine for 3 weeks. The patients received 15 mg mirtazapine on day 0; 30 mg mirtazapine on day 1; and 45 mg mirtazapine per day from day 2 to the end of the study (day 21). UFC excretion was measured before treatment (day 1), at the beginning (day 0), after 1 week (day 7) and after 3 weeks (day 21) of treatment with mirtazapine. Urine samples were collected from 08:00 to 08:00 h the following day. On the days of urine sampling, the severity of depressive symptoms was assessed using the 21-item version of the Hamilton Rating Scale for Depression (21-HAMD). There was a significant reduction of UFC excretion during 3-week mirtazapine therapy, which was already obvious after the first day of treatment (day 0). However, there were no significant across-subjects correlations between UFC reduction and decrease in 21-HAMD sum scores. Apparently, the mirtazapine-induced rapid reduction of cortisol secretion in depressed patients is not necessarily correlated with a favorable therapeutic response."
 

dookie

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Cyproheptadine also lowers cortisol, yet it still makes me feel strange and overall bad
 

mujuro

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It also lowers DHEA-S. It gave me severe asthenia, so I couldn't continue using it.
 

haidut

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All serotonin antagonists, especially ones acting at 5-HT2 and less so at 5-HT1, would do it. 5-HT5, 5-HT6, and 5-HT7 antagonists may also do it but I think they may be more tissue-selective. There are a few 5-HT6/7 antagonists in clinical trials right now, mostly for neurological conditions like AD, and lower cortisol was definitely noticed.
 
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DaveFoster

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@dookie Cypro is a potent D3 antagonist, so you might feel anhedonia from it.

@mujuro Interesting; I only use doses under 1 mg, so I haven't experienced that. I've actually experienced a strength increase. I think the key is to use it at an inhibitory dose, and at the lowest possible dose.

@haidut 5-HT2 antagonism is what extended lifespan in the studies you posted. That receptor for cortisol, anti-histamines should lower histamine (obviously), and do you know of the most effective ways to lower ammonia besides thiamine? I remember you talking about it on a Generative Energy podcast, so I'll have to go check that out.

As you've mentioned, lowering histamine, serotonin, and ammonia seem like the ways to go for keeping NO low, and increasing health and longevity.
 

Regina

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@dookie Cypro is a potent D3 antagonist, so you might feel anhedonia from it.

@mujuro Interesting; I only use doses under 1 mg, so I haven't experienced that. I've actually experienced a strength increase. I think the key is to use it at an inhibitory dose, and at the lowest possible dose.

@haidut 5-HT2 antagonism is what extended lifespan in the studies you posted. That receptor for cortisol, anti-histamines should lower histamine (obviously), and do you know of the most effective ways to lower ammonia besides thiamine? I remember you talking about it on a Generative Energy podcast, so I'll have to go check that out.

As you've mentioned, lowering histamine, serotonin, and ammonia seem like the ways to go for keeping NO low, and increasing health and longevity.
Does cypro (and other anti-serotonin) also lower NO?
 
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DaveFoster

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Does cypro (and other anti-serotonin) also lower NO?
Cyproheptadine does. Mirtazapine doesn't seem to increase NOS in the brain like other antidepressants, so it probably lowers brain inflammation.

Antidepressant action via the nitric oxide system: A pilot study in an acute depressive model induced by arginin. - PubMed - NCBI

"Nitric oxide (NO) may be a neurotransmitter related to major depressive disorder (MDD) because the selective neuronal NO synthase (NOS) inhibitor, 7-nitroindazole, induces dose-dependent antidepressant-like effects. However, its role in MDD is not yet known. The purpose of our study was to determine if antidepressants improve depression via the NO pathway using an acute depressive rat model induced by L-arginine (AR). Three types of antidepressants were examined, fluoxetine (FLX, 10 mg/kg), milnacipran (MIL, 30 mg/kg), and mirtazapine (MIR, 10 mg/kg), in a depressive model that used AR (750 mg/kg) pretreatment. mRNA expression levels of three NOS subtypes were analyzed by real-time PCR, as well as serum NO levels. Significant increases in iNOS mRNA expression levels were found in brain regions after AR treatment, although the eNOS gene tended to decrease with AR injection. After antidepressant treatment, there were no mRNA expression changes in either nNOS or iNOS. However, eNOS mRNA expression significantly increased with FLX (cerebellum, P=0.011; hippocampus, P=0.011; midbrain, P=0.011; pons, P=0.013; striatum, P=0.011; and thalamus, P<0.001). There was a statistically significant increase in serum NO levels with MIL treatment (P=0.011). We conclude that changes in eNOS mRNA levels in the brain with FLX treatment, and amount of serum NO with MIL treatment may be related to antidepressant effects of both agents, but further experiments are needed to confirm involvement of the NO system in MDD."
 

Regina

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Cyproheptadine does. Mirtazapine doesn't seem to increase NOS in the brain like other antidepressants, so it probably lowers brain inflammation.

Antidepressant action via the nitric oxide system: A pilot study in an acute depressive model induced by arginin. - PubMed - NCBI

"Nitric oxide (NO) may be a neurotransmitter related to major depressive disorder (MDD) because the selective neuronal NO synthase (NOS) inhibitor, 7-nitroindazole, induces dose-dependent antidepressant-like effects. However, its role in MDD is not yet known. The purpose of our study was to determine if antidepressants improve depression via the NO pathway using an acute depressive rat model induced by L-arginine (AR). Three types of antidepressants were examined, fluoxetine (FLX, 10 mg/kg), milnacipran (MIL, 30 mg/kg), and mirtazapine (MIR, 10 mg/kg), in a depressive model that used AR (750 mg/kg) pretreatment. mRNA expression levels of three NOS subtypes were analyzed by real-time PCR, as well as serum NO levels. Significant increases in iNOS mRNA expression levels were found in brain regions after AR treatment, although the eNOS gene tended to decrease with AR injection. After antidepressant treatment, there were no mRNA expression changes in either nNOS or iNOS. However, eNOS mRNA expression significantly increased with FLX (cerebellum, P=0.011; hippocampus, P=0.011; midbrain, P=0.011; pons, P=0.013; striatum, P=0.011; and thalamus, P<0.001). There was a statistically significant increase in serum NO levels with MIL treatment (P=0.011). We conclude that changes in eNOS mRNA levels in the brain with FLX treatment, and amount of serum NO with MIL treatment may be related to antidepressant effects of both agents, but further experiments are needed to confirm involvement of the NO system in MDD."
:thumbsup:
 
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DaveFoster

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It also lowers DHEA-S. It gave me severe asthenia, so I couldn't continue using it.
https://www.ncbi.nlm.nih.gov/pubmed/18706658

BACKGROUND:
Among the neuroactive steroids, dehydroepiandrosterone sulfate (DHEA-S) is at least in part produced in the adrenal gland and is therefore under the control of the hypothalamic-pituitary-adrenocortical (HPA)-system. In the present study, the impact of mirtazapine on DHEA-S and cortisol (COR) levels was investigated in relation to clinical response in depressed patients.

METHODS:
A total of 23 inpatients suffering from a major depressive episode (DSM-IV criteria) underwent 5-week treatment with mirtazapine (45 mg/day). Plasma samples were taken weekly at 0800 h and quantified for COR and DHEA-S levels.

RESULTS:
Mirtazapine significantly reduced both COR and DHEA-S concentrations, but had no impact on the COR/DHEA-S ratio. The percentage decrease of DHEA-S, but not that of COR was significantly and positively correlated with the percentage reduction in the sum score of the Hamilton Depression Rating Scale at week 5, suggesting a relationship between DHEA-S reduction and clinical efficacy of mirtazapine. There was a significant positive correlation between the decline in COR and DHEA-S levels.

CONCLUSIONS:
Apparently, the decrease in COR and DHEA-S concentrations conjointly reflects an attenuating impact of mirtazapine on HPA axis activity, thereby decreasing the adrenal secretion of COR and DHEA-S.
 

bionicheart

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Hey I was recently prescribed mirtazapine for anxiety/insomnia, 15mg. I was feeling tired the first couple days, then really great (anxiety free/relaxed) the one morning I was super anxious (maybe increased adrenaline) so I stopped taking it. (total of 5 days)
@DaveFoster are you still taking a low dose and how does it help you? I want to try it again because I had two days of complete contentment and no social anxiety at work. But should I give it a full month to start working at that dose? My doctor said to keep taking it despite the anxiety, but I just couldn't handle it.... any input would be appreciated since you seem very knowledgable about this drug! I'm only 27, don't know if this helps..
Thanks!!
 
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DaveFoster

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Hey I was recently prescribed mirtazapine for anxiety/insomnia, 15mg. I was feeling tired the first couple days, then really great (anxiety free/relaxed) the one morning I was super anxious (maybe increased adrenaline) so I stopped taking it. (total of 5 days)
@DaveFoster are you still taking a low dose and how does it help you? I want to try it again because I had two days of complete contentment and no social anxiety at work. But should I give it a full month to start working at that dose? My doctor said to keep taking it despite the anxiety, but I just couldn't handle it.... any input would be appreciated since you seem very knowledgable about this drug! I'm only 27, don't know if this helps..
Thanks!!
You should take your temperature and pulse throughout the day. Mirtazapine can trigger hyperthyroidism, especially if you continued to drink coffee. 15 mg is a high starting dose.
 
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DaveFoster

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I just wanted to point out that one of the studies I posted also found decreased prolactin concentrations in addition to cortisol, so mirtazapine may aid hyperprolactinemia.

Endocrinological effects of mirtazapine in healthy volunteers. - PubMed - NCBI

"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."
 

Loachi1105

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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.
I don’t know if it is correlated to Mirtazapine or not, I don’t know.
But I have been using Mirtazapine for 8 years.
Over that period of time my morning Cortisol raised from high in the range to a few point OVER the range.
What I see here is they administered Mirtazapine at 8:AM , and saw COR lower 4 hours later.
That is , seems to me just normal , as I understand COR is at his highest at 8:AM end naturally goes down during day.
Second point is that I wonder if you take Mirtazapine at late evening, if COR does not come back with a vengeance. Effect that is also seen with ex Naltrexone that blocks endorfine , but result is a endorfine spike after Naltrexone looses its effect.
It is not really completely comparable as Naltrexone does not lower endorfine , but just blocks the endorfine receptor , giving you system a signal endorfine is to low, resulting in a spike.

But nevertheless, for a reason I do not know enough about, I can imagine that if Mirtazapine puts down COR output, afterward your system could try to restore what it reckons is the adequate COR level with a spike.
( As for the 24 urinary output, if it has been lowered for a few hours it can still be lower despite the spike afterwards , if the lowering is longer/stronger than the spike. ) ( My 24h free COR collect is also still just bellow the top of the the range, even if my morning readings are always to high )
Gives me the idea of taking a Mirtazapine in the very early morning before next COR test.
 

bionicheart

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I don’t know if it is correlated to Mirtazapine or not, I don’t know.
But I have been using Mirtazapine for 8 years.
Over that period of time my morning Cortisol raised from high in the range to a few point OVER the range.
What I see here is they administered Mirtazapine at 8:AM , and saw COR lower 4 hours later.
That is , seems to me just normal , as I understand COR is at his highest at 8:AM end naturally goes down during day.
Second point is that I wonder if you take Mirtazapine at late evening, if COR does not come back with a vengeance. Effect that is also seen with ex Naltrexone that blocks endorfine , but result is a endorfine spike after Naltrexone looses its effect.
It is not really completely comparable as Naltrexone does not lower endorfine , but just blocks the endorfine receptor , giving you system a signal endorfine is to low, resulting in a spike.

But nevertheless, for a reason I do not know enough about, I can imagine that if Mirtazapine puts down COR output, afterward your system could try to restore what it reckons is the adequate COR level with a spike.
( As for the 24 urinary output, if it has been lowered for a few hours it can still be lower despite the spike afterwards , if the lowering is longer/stronger than the spike. ) ( My 24h free COR collect is also still just bellow the top of the the range, even if my morning readings are always to high )
Gives me the idea of taking a Mirtazapine in the very early morning before next COR test.

@Loachi1105 That's interesting about the spike in cortisol. I started taking 7.5mg around 9pm(to help sleep) 3 nights ago. this afternoon I feel like I'm running on adrenaline, despite adequate gluose/protein! This is the reason I stopped taking it a couple months ago. (Took 15mg at night for 4 days and quit because i had a panic attack, OCD symptoms increased) I don't mean to pry, but do you mind telling me why you're taking it and what dose/time of day you take it...? I'm looking to eradicate my anxiety and ocd--I was prescribed mirtaz and they told me to push through this period of increased anxiety. but it's making me feel crazy. thanks in advance! :)
 

Loachi1105

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@Loachi1105 That's interesting about the spike in cortisol. I started taking 7.5mg around 9pm(to help sleep) 3 nights ago. this afternoon I feel like I'm running on adrenaline, despite adequate gluose/protein! This is the reason I stopped taking it a couple months ago. (Took 15mg at night for 4 days and quit because i had a panic attack, OCD symptoms increased) I don't mean to pry, but do you mind telling me why you're taking it and what dose/time of day you take it...? I'm looking to eradicate my anxiety and ocd--I was prescribed mirtaz and they told me to push through this period of increased anxiety. but it's making me feel crazy. thanks in advance! :)
Your story sounds familiar, but I noticed the neg effect rather in long time use, OR I did at that time not make the relationship between the Mirtazapine and the anxiety.
But I must emphasize, I don't know if there is a relationship, can be coincidence.
If you google Mirtazapine & anxiety, your find many stories linking the 2, but then, if someone is prescribed Mirta its because there is already something going wrong......
You'l find my whole story here:
Mirtazapine Experiences
 
Last edited:

bionicheart

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Your story sounds familiar, but I noticed the neg effect rather in long time use, OR I did at that time not make the relationship between the Mirtazapine and the anxiety.
But I must emphasize, I don't know if there is a relationship, can be coincidence.
If you google Mirtazapine & anxiety, your find many stories linking the 2, but then, if someone is prescribed Mirta its because there is already something going wrong......
You'l find my whole story here:
Mirtazapine Experiences
Thanks for sharing. I was on benzos for 6 years, and just got back on them a few months ago, now regretting it and tapering off again. I'm new here too, and have yet to banish these anxiety demons... HOWEVER, I'm already feeling better eating more peaty for only a month and have found this forum to be a goldmine as far as nutrition and the link to serotonin/mental health, etc... I'm hopeful you'll find some help here. welcome! :)
 
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DaveFoster

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I don’t know if it is correlated to Mirtazapine or not, I don’t know.
But I have been using Mirtazapine for 8 years.
Over that period of time my morning Cortisol raised from high in the range to a few point OVER the range.
What I see here is they administered Mirtazapine at 8:AM , and saw COR lower 4 hours later.
That is , seems to me just normal , as I understand COR is at his highest at 8:AM end naturally goes down during day.
Second point is that I wonder if you take Mirtazapine at late evening, if COR does not come back with a vengeance. Effect that is also seen with ex Naltrexone that blocks endorfine , but result is a endorfine spike after Naltrexone looses its effect.
It is not really completely comparable as Naltrexone does not lower endorfine , but just blocks the endorfine receptor , giving you system a signal endorfine is to low, resulting in a spike.

But nevertheless, for a reason I do not know enough about, I can imagine that if Mirtazapine puts down COR output, afterward your system could try to restore what it reckons is the adequate COR level with a spike.
( As for the 24 urinary output, if it has been lowered for a few hours it can still be lower despite the spike afterwards , if the lowering is longer/stronger than the spike. ) ( My 24h free COR collect is also still just bellow the top of the the range, even if my morning readings are always to high )
Gives me the idea of taking a Mirtazapine in the very early morning before next COR test.
8 years is enough time to raise cortisol over the top-end of the range, especially if you're consuming high PUFA foods (where the appetite-stimulating effect of mirtazapine would exacerbate PUFA accumulation). There's no mechanism by which mirtazapine would raise cortisol, and it's anti-serotonin effects would logically lead to the opposite unless you have large amounts of fat accumulation ---> increased leptin ----> signaled upregulation of estrogen in tissues ----> increased cortisol production.
 

kaybb

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Cyproheptadine does. Mirtazapine doesn't seem to increase NOS in the brain like other antidepressants, so it probably lowers brain inflammation.

Antidepressant action via the nitric oxide system: A pilot study in an acute depressive model induced by arginin. - PubMed - NCBI

"Nitric oxide (NO) may be a neurotransmitter related to major depressive disorder (MDD) because the selective neuronal NO synthase (NOS) inhibitor, 7-nitroindazole, induces dose-dependent antidepressant-like effects. However, its role in MDD is not yet known. The purpose of our study was to determine if antidepressants improve depression via the NO pathway using an acute depressive rat model induced by L-arginine (AR). Three types of antidepressants were examined, fluoxetine (FLX, 10 mg/kg), milnacipran (MIL, 30 mg/kg), and mirtazapine (MIR, 10 mg/kg), in a depressive model that used AR (750 mg/kg) pretreatment. mRNA expression levels of three NOS subtypes were analyzed by real-time PCR, as well as serum NO levels. Significant increases in iNOS mRNA expression levels were found in brain regions after AR treatment, although the eNOS gene tended to decrease with AR injection. After antidepressant treatment, there were no mRNA expression changes in either nNOS or iNOS. However, eNOS mRNA expression significantly increased with FLX (cerebellum, P=0.011; hippocampus, P=0.011; midbrain, P=0.011; pons, P=0.013; striatum, P=0.011; and thalamus, P<0.001). There was a statistically significant increase in serum NO levels with MIL treatment (P=0.011). We conclude that changes in eNOS mRNA levels in the brain with FLX treatment, and amount of serum NO with MIL treatment may be related to antidepressant effects of both agents, but further experiments are needed to confirm involvement of the NO system in MDD."
Milnacipran (Savella) was prescribed to me today as a treatment for fibromyalgia pain and fatigue. Have you heard of this medicine or tried it for pain and fatigue? I'm scared of it after reading on forum about SSRI, (this is a SNRI). I think they have the same risks? And this study saying it increases NO? So this scares me also ! But I would love to find something to help. Also, IYO, is LDN a much better choice? I have been off and on it. It totally wipes me out, kicking up my fibro/thyroid symptoms but going off LDN I can feel it does something. This doctor isn't prescribing LDN yet for fibro so she wasn't familiar enough with that option. I get my LDN from another doc. The appointment with this doctor was thorough and not rushed, and lots of discussion about my past and present health. I have an appointment with my LDN doctor coming up and need to decide between the two. I would much appreciate your opinions. (side note, I am already on Armor thyroid, for hypothyroidism, so I need more than thyroid medicine, also doing RP almost 2 years. Thanks in advance....
@DaveFoster
 
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DaveFoster

DaveFoster

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Milnacipran (Savella) was prescribed to me today as a treatment for fibromyalgia pain and fatigue. Have you heard of this medicine or tried it for pain and fatigue? I'm scared of it after reading on forum about SSRI, (this is a SNRI). I think they have the same risks? And this study saying it increases NO? So this scares me also ! But I would love to find something to help. Also, IYO, is LDN a much better choice? I have been off and on it. It totally wipes me out, kicking up my fibro/thyroid symptoms but going off LDN I can feel it does something. This doctor isn't prescribing LDN yet for fibro so she wasn't familiar enough with that option. I get my LDN from another doc. The appointment with this doctor was thorough and not rushed, and lots of discussion about my past and present health. I have an appointment with my LDN doctor coming up and need to decide between the two. I would much appreciate your opinions. (side note, I am already on Armor thyroid, for hypothyroidism, so I need more than thyroid medicine, also doing RP almost 2 years. Thanks in advance....
@DaveFoster
I no longer have any fibromylagia symptoms. I will make a Foster Your Health Podcast episode on the topic. Do you take progesterone or aspirin? There are quite a few drugs that can treat the symptoms of fibromyalgia.
 

kaybb

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I no longer have any fibromylagia symptoms. I will make a Foster Your Health Podcast episode on the topic. Do you take progesterone or aspirin? There are quite a few drugs that can treat the symptoms of fibromyalgia.
Yes, progesterone ..going for blood tests and will see if I can up it. And aspirin, I have to be careful because of stomach burning/pain. It doesn't seem to help too much with pain...but maybe in long run it would help. Are there better drugs than Savella ? Looking forward to podcast . Will I find it here on forum?
 

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