Best drug to increase hunger on bulking?

[MONSTRO]

Witch is your best option to increase the hunger during the off season ?

MK677 ?
GHRP6?
Di Histine?

All the produts you use to increase hunger gives you lethargy and sleepiness , we know because sleepiness is a sign of anabolism .

[Vision]

Witch is your best option to increase the hunger during the off season ?

MK677 ?
GHRP6?
Di Histine?

All the produts you use to increase hunger gives you lethargy and sleepiness , we know because sleepiness is a sign of anabolism .

There's a few drugs and medications out there and most have off label properties for this. Of all drugs, from GHRP"s, some antihistamines and so on..

Here's a medication I used to help with anxiety and depression, I had nbo clue that it had other off label properties that began to show after I took this drug, upon researching it became ne of the best things I just randomly tried that had everything I was looking for.

I have had my bouts with depression here and there and tried medication after medication throughout the years..
Often at times when I have a low my appetite naturally takes a hit as well I would struggle to choke down food all the while trying to have a stable steady keel with my outlook..

A few years ago I introduced a drug that I was kinda unfamiliar with, yet didn't know a whole lot about, after I did some research on it it turned out to be the Swiss army knife of antidepressants and hunger, sleep.

Its role is multi-functional, at the same time not effecting sex drive, libido, ability to climax or anything that SSIR's do to people..

This drug has been amazing not only did it treat my depression symptoms it helped with my sleep much like an ambien would (deep sleep wise).. It has been used to treat people with wasting disorders where they cant eat, or lack of appetite, anorexia..In fact its one of the top 3 most prescribed for treating appetite stimulation.. Dosages will vary.. I started at 30mgs and I was blown away on how well I was sleeping, and the increase and desire to eat was increased to a whole different level sometimes unconformable, it actually became problematic at night.

side effects? zero for me.... maybe a bit groggy upon waking up nothing a dark roast can't fix...

Here's some info below.

Mirtazapine, sold under the brand name Remeron among others, is an atypical antidepressant which is used primarily in the treatment of depression. In addition to its antidepressant properties, mirtazapine has anxiolytic, sedative, antiemetic, and appetite stimulant effects and is sometimes used in the treatment of anxiety disorders, insomnia, nausea and vomiting, and to produce weight gain when desirable. It is taken by mouth.
The drug acts as an antagonist of certain adrenergic and serotonin receptors, and is also a strong antihistamine. It is sometimes described as a noradrenergic and specific serotonergic antidepressant (NaSSA), although the actual evidence in support of this label has been regarded as poor. Chemically, mirtazapine is a tetracyclic antidepressant (TeCA), with four interconnected rings of atoms, and is a relative of the TeCA mianserin(Tolvon).
Mirtazapine was developed by Organon International in the Netherlands and was introduced in the United States in 1996.[4] Its patent expired in 2004, so generic versions are available.

Approved and off-label

Mirtazapine's primary use is the treatment of major depressive disorder and other mood disorders.
However, it has also been found useful in alleviating the following conditions and is sometimes prescribed off-label for their treatment:

Generalized anxiety disorder
Social anxiety disorder
Obsessive–compulsive disorder
Panic disorder
Post-traumatic stress disorder
Low appetite/underweight
Insomnia
Nausea and vomiting
Itching
Headaches and migraine

Effectiveness and tolerability

In 2010 NICE published a guideline for treating depression that included a review of antidepressants. It recommended generic SSRIs as first line choices, as they are "equally effective as other antidepressants and have a favourable risk–benefit ratio." With respect to mirtazapine, it found: "There is no difference between mirtazapine and other antidepressants on any efficacy measure, although in terms of achieving remission mirtazapine appears to have a statistical though not clinical advantage. In addition, mirtazapine has a statistical advantage over SSRIs in terms of reducing symptoms of depression, but the difference is not clinically important. However, there is strong evidence that patients taking mirtazapine are less likely to leave treatment early because of side effects, although this is not the case for patients reporting side effects or leaving treatment early for any reason.
A 2011 Cochrane review that compared mirtazapine to other antidepressants, found that while it appears to have a faster onset in people for whom it works (measured at 2 weeks), it is about the same as other antidepressants at 6 weeks.
A 2012 review focused on antidepressants and sleep found that in many people with sleep disorders caused by depression, mirtazapine reduces the time it takes to fall asleep and increases the quality of sleep, but that in some people it can disturb sleep, causing restless leg syndrome in 8 to 28% of people, and in rare cases causes REM sleep behavior disorder.

A 2018 systematic review and network meta-analysis comparing the efficacy and acceptability of 21 antidepressant drugs showed mirtazapine to be one of the most effective antidepressants in head-to-head studies.

In general, all antidepressants, including mirtazapine, require at least a week for their therapeutic benefits on depressive and anxious symptoms to become apparent.

Side effects

A 2011 Cochrane review found that compared with other antidepressants, it is more likely to cause weight gain and sleepiness, but it is less likely to cause tremor than tricyclic antidepressants, and less likely to cause nausea and sexual dysfunction than SSRIs.
Very common (≥10% incidence) adverse effects include constipation, dry mouth, sleepiness, increased appetite and weight gain.

Common (1–10% incidence) adverse effects include weakness, confusion, dizziness, peripheral edema, and negative lab results like elevated transaminases, elevated serum triglycerides, and elevated total cholesterol.[6]
Mirtazapine is not considered to have a risk of many of the side effects often associated with other antidepressants like the SSRIs, and may actually improve certain ones when taken in conjunction with them. (Those adverse effects include decreased appetite, weight loss, insomnia, nausea and vomiting, diarrhoea, urinary retention, increased body temperature, excessive sweating, pupil dilation and sexual dysfunction.

In general, some antidepressants, especially SSRIs, can paradoxically exacerbate some peoples' depression or anxiety or cause suicidal ideation.[43] Despite its sedating action, mirtazapine is also believed to be capable of this, so in the United States and certain other countries, it carries a black box label warning of these potential effects.
A case report published in 2000 noted an instance in which mirtazapine counteracted the action of clonidine, causing a dangerous rise in blood pressure.

Discontinuation

Mirtazapine and other antidepressants may cause a discontinuation syndrome upon cessation. A gradual and slow reduction in dose is recommended to minimize discontinuation symptoms. Effects of sudden cessation of treatment with mirtazapine may include depression, anxiety, panic attacks, vertigo, restlessness, irritability, decreased appetite, insomnia, diarrhea, nausea, vomiting, flu-like symptoms such as allergies and pruritus, headaches and sometimes hypomania or mania.

Overdose

Mirtazapine is considered to be relatively safe in the event of an overdose, although it is considered slightly more toxic in overdose than most of the SSRIs (except citalopram). Unlike the tricyclic antidepressants, mirtazapine showed no significant cardiovascularadverse effects at 7 to 22 times the maximum recommended dose. Case reports of overdose with as much as 30 to 50 times the standard dose described the drug as relatively nontoxic, compared to tricyclic antidepressants.
Twelve reported fatalities have been attributed to mirtazapine overdose. The fatal toxicity index (deaths per million prescriptions) for mirtazapine is 3.1 (95% CI: 0.1 to 17.2). This is similar to that observed with SSRIs.
Interactions

Concurrent use with inhibitors or inducers of the cytochrome (CYP) P450 isoenzymes CYP1A2, CYP2D6, and/or CYP3A4 can result in altered concentrations of mirtazapine, as these are the main enzymes responsible for its metabolism. As examples, fluoxetine and paroxetine, inhibitors of these enzymes, are known to modestly increase mirtazapine levels, while carbamazepine, an inducer, considerably decreases them. Liver and moderate renal impairment have been reported to decrease the oral clearance of mirtazapine by about 30%; severe renal impairment decreases it by 50%.
According to information from the manufacturers, mirtazapine should not be started within two weeks of any monoamine oxidase inhibitor (MAOI) usage; likewise, MAOIs should not be administered within two weeks of discontinuing mirtazapine.[58] Mirtazapine in combination with an SSRI, SNRI, or TCA as an augmentation strategy is considered to be relatively safe and is often employed therapeutically, with a combination of venlafaxine and mirtazapine, sometimes referred to as "California rocket fuel".

Pharmacology

Values are Ki (nM). The smaller the value, the more strongly the drug binds to the site.
Mirtazapine has antihistamine, α2-blocker, and antiserotonergic activity.[7][67] It is specifically a potent antagonist or inverse agonist of the α2A-, α2B-, and α2C-adrenergic receptors, the serotonin 5-HT2A, 5-HT2C, and 5-HT3receptors, and the histamine H1 receptor.[7][67] Unlike many other antidepressants, it does not inhibit the reuptake of serotonin, norepinephrine, or dopamine, nor does it inhibit monoamine oxidase.[68] Similarly, mirtazapine has weak or no activity as an anticholinergic or blocker of sodium or calcium channels, in contrast to most TCAs. In accordance, it has better tolerability and low toxicity in overdose. As an H1 receptor antagonist, mirtazapine is extremely potent, and is in fact the most potent of all the TCAs and TeCAs. Antagonism of the H1 receptor is by far the strongest activity of mirtazapine, with the drug acting as a selective H1receptor antagonist at low concentrations.
The (S)-(+) enantiomer of mirtazapine is responsible for antagonism of the serotonin 5-HT2A and 5-HT2C receptors,
while the (R)-(–) enantiomer is responsible for antagonism of the 5-HT3 receptor.[11] Both enantiomers are involved in antagonism of the H1 and α2-adrenergic receptors, although the (S)-(+) enantiomer is the stronger antihistamine.

Although not clinically relevant, mirtazapine has been found to act as a partial agonist of the κ-opioid receptor at high concentrations (EC50 = 7.2 μM).
α2-Adrenergic receptor

Antagonism of the α2-adrenergic receptors, which function largely as inhibitory autoreceptors and heteroreceptors, enhances adrenergic and serotonergic neurotransmission, notably central 5-HT1A receptor mediated transmission in the dorsal raphe nucleus and hippocampus; hence, mirtazapine's classification as a NaSSA. Indirect α1 adrenoceptor-mediated enhancement of serotonin cell firing and direct blockade of inhibitory α2heteroreceptors located on serotonin terminals are held responsible for the increase in extracellular serotonin. Because of this, mirtazapine has been said to be a functional "indirect agonist" of the 5-HT1Areceptor. Increased activation of the central 5-HT1A receptor is thought to be a major mediator of efficacy of most antidepressant drugs.

5-HT2 and 5-HT3 receptors

Antagonism of the 5-HT2 subfamily of receptors and inverse agonism of the 5-HT2C receptor appears to be in part responsible for mirtazapine's efficacy in the treatment of depressive states. Mirtazapine increases dopamine release in the prefrontal cortex. Accordingly, it was shown that by blocking the α2-adrenergic receptors and 5-HT2C receptors mirtazapine disinhibited dopamine and norepinephrine activity in these areas in rats.[82] In addition, mirtazapine's antagonism of 5-HT2A receptors has beneficial effects on anxiety, sleep and appetite, as well as sexual function regarding the latter receptor.[7][42] Mirtazapine has been shown to lower drug seeking behaviour in various human and animal studies. It is also being investigated in substance abuse disorders to reduce withdrawal effects and improve remission rates.

Antagonism of the 5-HT3 receptor, an action mirtazapine shares with the approved antiemetic ondansetron, significantly improves pre-existing symptoms of nausea, vomiting, diarrhea, and irritable bowel syndrome in afflicted individuals.[89] Mirtazapine may be used as an inexpensive antiemetic alternative to ondansetron.[24] Blockade of the 5-HT3 receptors has also shown to improve anxiety and to be effective in the treatment of drug addiction in several studies.[90] In conjunction with substance abuse counseling, mirtazapine has been investigated for the purpose of reducing methamphetamine use in dependent individuals with success.[84] In contrast to mirtazapine, the SSRIs, SNRIs, MAOIs, and some TCAs increase the general activity of the 5-HT2A, 5-HT2C, and 5-HT3 receptors leading to a host of negative changes and side effects, the most prominent of which including anorexia, insomnia, sexual dysfunction (loss of libido and anorgasmia), nausea, and diarrhea, among others. As a result, it is often combined with these drugs to reduce their side-effect profile and to produce a stronger antidepressant effect.

Mirtazapine does not have serotonergic activity and does not cause serotonergic side effects or serotonin syndrome.

This is in accordance with the fact that it is not a serotonin reuptake inhibitor or MAOI, nor a serotonin receptor agonist.
There are no reports of serotonin syndrome in association with mirtazapine alone, and mirtazapine has not been found to cause serotonin syndrome in overdose.[9][92][93] However, there are a handful of case reports of serotonin syndrome occurring with mirtazapine in combination with serotonergic drugs like SSRIs, although such reports are unusual, very rare, and do not necessarily implicate mirtazapine as causative.The addition of mirtazapine to an MAOI does not cause serotonin syndrome, and has been considered to be a safe combination.[9][92] Moreover, mirtazapine may actually be useful in the treatment of serotonin syndrome, with at least one publication finding it to be effective in resolving the syndrome. This is in accordance with the fact that the 5-HT2A receptor is the predominant serotonin receptor thought to be involved in the pathophysiology of serotonin syndrome (with the 5-HT1A receptor seeming to be protective). Mirtazapine is a potent 5-HT2A receptor antagonist, and cyproheptadine, a drug that shares this property, mediates recovery from serotonin syndrome and is well-established clinically as an antidote against it.

H1 receptor

Mirtazapine is a very strong H1 receptor inverse agonist and, as a result, it can cause powerful sedative and hypnotic effects.[7] A single 15 mg dose of mirtazapine to healthy volunteers has been found to result in over 80% occupancy of the H1 receptor and to induce intense sleepiness.[72] After a short period of chronic treatment, however, the H1 receptor tends to desensitize and the antihistamine effects become more tolerable. Many patients may also dose at night to avoid the effects, and this appears to be an effective strategy for combating them. Blockade of the H1 receptor may improve pre-existing allergies, pruritus, nausea, and insomnia in afflicted individuals. It may also contribute to weight gain, however. In contrast to the H1 receptor, mirtazapine has only low affinity for the muscarinic acetylcholine receptors, although anticholinergic side effects like dry mouth, constipation, and mydriasis are still sometimes seen in clinical practice.

Pharmacokinetics

The oral bioavailability of mirtazapine is about 50%. It is found mostly bound to plasma proteins, about 85%. It is metabolized primarily in the liver by demethylation and hydroxylation via cytochrome P450 enzymes. One of its major metabolites is desmethylmirtazapine. The overall elimination half-life is 20–40 hours. About 15% is eliminated in feces and 75% in urine.

History

Mirtazapine was first synthesized at Organon and published in 1989, was first approved for use in major depressive disorder in the Netherlands in 1994, and was introduced in the United States in 1996 under the brand name Remeron.

Society and culture

A 15 mg tablet of generic mirtazapine.

Generic names

Mirtazapine is the English and French generic name of the drug and its INN, USAN, USP, BAN, DCF, and JAN.
Its generic name in Spanish is mirtazapina, in German is Mirtazapin, and in Latin is mirtazapinum.
Brand names

Mirtazapine is marketed under many brand names worldwide, including Adco-Mirteron, Afloyan, Amirel, Arintapin Smelt, Avanza, Azapin, Beron, Bilanz, Calixta, Ciblex, Combar, Comenter, Depreram, Divaril, Esprital, Maz, Menelat, Mepirzapine, Merdaten, Meronin, Mi Er Ning, Milivin, Minelza, Minivane, Mirastad, Mirazep, Miro, Miron, Mirrador, Mirt, Mirta, Mirtabene, Mirtadepi, Mirtagamma, Mirtagen, Mirtalan, Mirtamor, Mirtamylan, Mirtan, Mirtaneo, Mirtapax, Mirtapil, Mirtapine, Mirtaron, Mirtastad, Mirtax, Mirtaz, Mirtazap, Mirtazapin, Mirtazapina, Mirtazapine, Mirtazapinum, Mirtazelon, Mirtazon, Mirtazonal, Mirtel, Mirtimash, Mirtin, Mirtine, Mirzapine, Mirzaten, Mirzest, Mitaprex, Mitaxind, Mitocent, Mitrazin, Mizapin, Motofen, Mytra, Norset, Noxibel, Pharmataz, Promyrtil, Ramure, Redepra, Reflex, Remergil, Remergon, Remeron, Remirta, Rexer, Saxib, Sinmaron, Smilon, Tazepin, Tazimed, Tetrazic, Tifona, U-Mirtaron, U-zepine, Valdren, Vastat, Velorin, Yarocen, Zania, Zapex, Zestat, Zismirt, Zispin, Zuleptan, and Zulin.

Chemistry

Mirtazapine is a tetracyclic piperazinoazepine; mianserin was developed by the same team of organic chemists and mirtazapine differs from it via addition of a nitrogen atom in one of the rings. It is a racemic mixture of enantiomers. The (S)-(+)-enantiomer is known as esmirtazapine.
Analogues of mirtazapine include mianserin, setiptiline, and aptazapine.
Synthesis

A chemical synthesis of mirtazapine has been published.
Research

The use of mirtazapine has been explored in several additional conditions:

Sleep apnea/hypopnea
Inappropriate sexual behaviour and other secondary symptoms of autistic spectrum conditions and other pervasive developmental disorders
Antipsychotic-induced akathisia.
Drug withdrawal, dependence and detoxification
Negative, depressive and cognitive symptoms of schizophrenia (as an adjunct)
A case report has been published in which mirtazapine reduced visual hallucinations in a patient with Parkinson's disease psychosis (PDP).[121] This is in alignment with recent findings that inverse agonists at the 5-HT2A receptors are efficacious in attenuating the symptoms of Parkinson's disease psychosis. As is supported by the common practice of prescribing low-dose quetiapine and clozapine for PDP at doses too low to antagonize the D2 receptor, but sufficiently high doses to inversely agonize the 5-HT2A receptors.
Eight case reports have been reported in five papers on the use of mirtazapine in the treatment of hives as of 2017.

Veterinary use

Mirtazapine is sometimes prescribed as an appetite stimulant for cats or dogs experiencing anorexia due to medical conditions such as chronic kidney disease. It is especially useful for treating combined poor appetite and nausea in cats and dogs.

[MattDamon47]

I was put on mirtazapine after a stint in a mental hospital. Definetly helps you sleep and no sides really.

[Jozifp103]

Witch is your best option to increase the hunger during the off season ?

MK677 ?
GHRP6?
Di Histine?

All the produts you use to increase hunger gives you lethargy and sleepiness , we know because sleepiness is a sign of anabolism .

There's a few drugs and medications out there and most have off label properties for this. Of all drugs, from GHRP"s, some antihistamines and so on..

Here's a medication I used to help with anxiety and depression, I had nbo clue that it had other off label properties that began to show after I took this drug, upon researching it became ne of the best things I just randomly tried that had everything I was looking for.

I have had my bouts with depression here and there and tried medication after medication throughout the years..
Often at times when I have a low my appetite naturally takes a hit as well I would struggle to choke down food all the while trying to have a stable steady keel with my outlook..

A few years ago I introduced a drug that I was kinda unfamiliar with, yet didn't know a whole lot about, after I did some research on it it turned out to be the Swiss army knife of antidepressants and hunger, sleep.

Its role is multi-functional, at the same time not effecting sex drive, libido, ability to climax or anything that SSIR's do to people..

This drug has been amazing not only did it treat my depression symptoms it helped with my sleep much like an ambien would (deep sleep wise).. It has been used to treat people with wasting disorders where they cant eat, or lack of appetite, anorexia..In fact its one of the top 3 most prescribed for treating appetite stimulation.. Dosages will vary.. I started at 30mgs and I was blown away on how well I was sleeping, and the increase and desire to eat was increased to a whole different level sometimes unconformable, it actually became problematic at night.

side effects? zero for me.... maybe a bit groggy upon waking up nothing a dark roast can't fix...

Here's some info below.

Mirtazapine, sold under the brand name Remeron among others, is an atypical antidepressant which is used primarily in the treatment of depression. In addition to its antidepressant properties, mirtazapine has anxiolytic, sedative, antiemetic, and appetite stimulant effects and is sometimes used in the treatment of anxiety disorders, insomnia, nausea and vomiting, and to produce weight gain when desirable. It is taken by mouth.
The drug acts as an antagonist of certain adrenergic and serotonin receptors, and is also a strong antihistamine. It is sometimes described as a noradrenergic and specific serotonergic antidepressant (NaSSA), although the actual evidence in support of this label has been regarded as poor. Chemically, mirtazapine is a tetracyclic antidepressant (TeCA), with four interconnected rings of atoms, and is a relative of the TeCA mianserin(Tolvon).
Mirtazapine was developed by Organon International in the Netherlands and was introduced in the United States in 1996.[4] Its patent expired in 2004, so generic versions are available.

Approved and off-label

Mirtazapine's primary use is the treatment of major depressive disorder and other mood disorders.
However, it has also been found useful in alleviating the following conditions and is sometimes prescribed off-label for their treatment:

Generalized anxiety disorder
Social anxiety disorder
Obsessive–compulsive disorder
Panic disorder
Post-traumatic stress disorder
Low appetite/underweight
Insomnia
Nausea and vomiting
Itching
Headaches and migraine

Effectiveness and tolerability

In 2010 NICE published a guideline for treating depression that included a review of antidepressants. It recommended generic SSRIs as first line choices, as they are "equally effective as other antidepressants and have a favourable risk–benefit ratio." With respect to mirtazapine, it found: "There is no difference between mirtazapine and other antidepressants on any efficacy measure, although in terms of achieving remission mirtazapine appears to have a statistical though not clinical advantage. In addition, mirtazapine has a statistical advantage over SSRIs in terms of reducing symptoms of depression, but the difference is not clinically important. However, there is strong evidence that patients taking mirtazapine are less likely to leave treatment early because of side effects, although this is not the case for patients reporting side effects or leaving treatment early for any reason.
A 2011 Cochrane review that compared mirtazapine to other antidepressants, found that while it appears to have a faster onset in people for whom it works (measured at 2 weeks), it is about the same as other antidepressants at 6 weeks.
A 2012 review focused on antidepressants and sleep found that in many people with sleep disorders caused by depression, mirtazapine reduces the time it takes to fall asleep and increases the quality of sleep, but that in some people it can disturb sleep, causing restless leg syndrome in 8 to 28% of people, and in rare cases causes REM sleep behavior disorder.

A 2018 systematic review and network meta-analysis comparing the efficacy and acceptability of 21 antidepressant drugs showed mirtazapine to be one of the most effective antidepressants in head-to-head studies.

In general, all antidepressants, including mirtazapine, require at least a week for their therapeutic benefits on depressive and anxious symptoms to become apparent.

Side effects

A 2011 Cochrane review found that compared with other antidepressants, it is more likely to cause weight gain and sleepiness, but it is less likely to cause tremor than tricyclic antidepressants, and less likely to cause nausea and sexual dysfunction than SSRIs.
Very common (≥10% incidence) adverse effects include constipation, dry mouth, sleepiness, increased appetite and weight gain.

Common (1–10% incidence) adverse effects include weakness, confusion, dizziness, peripheral edema, and negative lab results like elevated transaminases, elevated serum triglycerides, and elevated total cholesterol.[6]
Mirtazapine is not considered to have a risk of many of the side effects often associated with other antidepressants like the SSRIs, and may actually improve certain ones when taken in conjunction with them. (Those adverse effects include decreased appetite, weight loss, insomnia, nausea and vomiting, diarrhoea, urinary retention, increased body temperature, excessive sweating, pupil dilation and sexual dysfunction.

In general, some antidepressants, especially SSRIs, can paradoxically exacerbate some peoples' depression or anxiety or cause suicidal ideation.[43] Despite its sedating action, mirtazapine is also believed to be capable of this, so in the United States and certain other countries, it carries a black box label warning of these potential effects.
A case report published in 2000 noted an instance in which mirtazapine counteracted the action of clonidine, causing a dangerous rise in blood pressure.

Discontinuation

Mirtazapine and other antidepressants may cause a discontinuation syndrome upon cessation. A gradual and slow reduction in dose is recommended to minimize discontinuation symptoms. Effects of sudden cessation of treatment with mirtazapine may include depression, anxiety, panic attacks, vertigo, restlessness, irritability, decreased appetite, insomnia, diarrhea, nausea, vomiting, flu-like symptoms such as allergies and pruritus, headaches and sometimes hypomania or mania.

Overdose

Mirtazapine is considered to be relatively safe in the event of an overdose, although it is considered slightly more toxic in overdose than most of the SSRIs (except citalopram). Unlike the tricyclic antidepressants, mirtazapine showed no significant cardiovascularadverse effects at 7 to 22 times the maximum recommended dose. Case reports of overdose with as much as 30 to 50 times the standard dose described the drug as relatively nontoxic, compared to tricyclic antidepressants.
Twelve reported fatalities have been attributed to mirtazapine overdose. The fatal toxicity index (deaths per million prescriptions) for mirtazapine is 3.1 (95% CI: 0.1 to 17.2). This is similar to that observed with SSRIs.
Interactions

Concurrent use with inhibitors or inducers of the cytochrome (CYP) P450 isoenzymes CYP1A2, CYP2D6, and/or CYP3A4 can result in altered concentrations of mirtazapine, as these are the main enzymes responsible for its metabolism. As examples, fluoxetine and paroxetine, inhibitors of these enzymes, are known to modestly increase mirtazapine levels, while carbamazepine, an inducer, considerably decreases them. Liver and moderate renal impairment have been reported to decrease the oral clearance of mirtazapine by about 30%; severe renal impairment decreases it by 50%.
According to information from the manufacturers, mirtazapine should not be started within two weeks of any monoamine oxidase inhibitor (MAOI) usage; likewise, MAOIs should not be administered within two weeks of discontinuing mirtazapine.[58] Mirtazapine in combination with an SSRI, SNRI, or TCA as an augmentation strategy is considered to be relatively safe and is often employed therapeutically, with a combination of venlafaxine and mirtazapine, sometimes referred to as "California rocket fuel".

Pharmacology

Values are Ki (nM). The smaller the value, the more strongly the drug binds to the site.
Mirtazapine has antihistamine, α2-blocker, and antiserotonergic activity.[7][67] It is specifically a potent antagonist or inverse agonist of the α2A-, α2B-, and α2C-adrenergic receptors, the serotonin 5-HT2A, 5-HT2C, and 5-HT3receptors, and the histamine H1 receptor.[7][67] Unlike many other antidepressants, it does not inhibit the reuptake of serotonin, norepinephrine, or dopamine, nor does it inhibit monoamine oxidase.[68] Similarly, mirtazapine has weak or no activity as an anticholinergic or blocker of sodium or calcium channels, in contrast to most TCAs. In accordance, it has better tolerability and low toxicity in overdose. As an H1 receptor antagonist, mirtazapine is extremely potent, and is in fact the most potent of all the TCAs and TeCAs. Antagonism of the H1 receptor is by far the strongest activity of mirtazapine, with the drug acting as a selective H1receptor antagonist at low concentrations.
The (S)-(+) enantiomer of mirtazapine is responsible for antagonism of the serotonin 5-HT2A and 5-HT2C receptors,
while the (R)-(–) enantiomer is responsible for antagonism of the 5-HT3 receptor.[11] Both enantiomers are involved in antagonism of the H1 and α2-adrenergic receptors, although the (S)-(+) enantiomer is the stronger antihistamine.

Although not clinically relevant, mirtazapine has been found to act as a partial agonist of the κ-opioid receptor at high concentrations (EC50 = 7.2 μM).
α2-Adrenergic receptor

Antagonism of the α2-adrenergic receptors, which function largely as inhibitory autoreceptors and heteroreceptors, enhances adrenergic and serotonergic neurotransmission, notably central 5-HT1A receptor mediated transmission in the dorsal raphe nucleus and hippocampus; hence, mirtazapine's classification as a NaSSA. Indirect α1 adrenoceptor-mediated enhancement of serotonin cell firing and direct blockade of inhibitory α2heteroreceptors located on serotonin terminals are held responsible for the increase in extracellular serotonin. Because of this, mirtazapine has been said to be a functional "indirect agonist" of the 5-HT1Areceptor. Increased activation of the central 5-HT1A receptor is thought to be a major mediator of efficacy of most antidepressant drugs.

5-HT2 and 5-HT3 receptors

Antagonism of the 5-HT2 subfamily of receptors and inverse agonism of the 5-HT2C receptor appears to be in part responsible for mirtazapine's efficacy in the treatment of depressive states. Mirtazapine increases dopamine release in the prefrontal cortex. Accordingly, it was shown that by blocking the α2-adrenergic receptors and 5-HT2C receptors mirtazapine disinhibited dopamine and norepinephrine activity in these areas in rats.[82] In addition, mirtazapine's antagonism of 5-HT2A receptors has beneficial effects on anxiety, sleep and appetite, as well as sexual function regarding the latter receptor.[7][42] Mirtazapine has been shown to lower drug seeking behaviour in various human and animal studies. It is also being investigated in substance abuse disorders to reduce withdrawal effects and improve remission rates.

Antagonism of the 5-HT3 receptor, an action mirtazapine shares with the approved antiemetic ondansetron, significantly improves pre-existing symptoms of nausea, vomiting, diarrhea, and irritable bowel syndrome in afflicted individuals.[89] Mirtazapine may be used as an inexpensive antiemetic alternative to ondansetron.[24] Blockade of the 5-HT3 receptors has also shown to improve anxiety and to be effective in the treatment of drug addiction in several studies.[90] In conjunction with substance abuse counseling, mirtazapine has been investigated for the purpose of reducing methamphetamine use in dependent individuals with success.[84] In contrast to mirtazapine, the SSRIs, SNRIs, MAOIs, and some TCAs increase the general activity of the 5-HT2A, 5-HT2C, and 5-HT3 receptors leading to a host of negative changes and side effects, the most prominent of which including anorexia, insomnia, sexual dysfunction (loss of libido and anorgasmia), nausea, and diarrhea, among others. As a result, it is often combined with these drugs to reduce their side-effect profile and to produce a stronger antidepressant effect.

Mirtazapine does not have serotonergic activity and does not cause serotonergic side effects or serotonin syndrome.

This is in accordance with the fact that it is not a serotonin reuptake inhibitor or MAOI, nor a serotonin receptor agonist.
There are no reports of serotonin syndrome in association with mirtazapine alone, and mirtazapine has not been found to cause serotonin syndrome in overdose.[9][92][93] However, there are a handful of case reports of serotonin syndrome occurring with mirtazapine in combination with serotonergic drugs like SSRIs, although such reports are unusual, very rare, and do not necessarily implicate mirtazapine as causative.The addition of mirtazapine to an MAOI does not cause serotonin syndrome, and has been considered to be a safe combination.[9][92] Moreover, mirtazapine may actually be useful in the treatment of serotonin syndrome, with at least one publication finding it to be effective in resolving the syndrome. This is in accordance with the fact that the 5-HT2A receptor is the predominant serotonin receptor thought to be involved in the pathophysiology of serotonin syndrome (with the 5-HT1A receptor seeming to be protective). Mirtazapine is a potent 5-HT2A receptor antagonist, and cyproheptadine, a drug that shares this property, mediates recovery from serotonin syndrome and is well-established clinically as an antidote against it.

H1 receptor

Mirtazapine is a very strong H1 receptor inverse agonist and, as a result, it can cause powerful sedative and hypnotic effects.[7] A single 15 mg dose of mirtazapine to healthy volunteers has been found to result in over 80% occupancy of the H1 receptor and to induce intense sleepiness.[72] After a short period of chronic treatment, however, the H1 receptor tends to desensitize and the antihistamine effects become more tolerable. Many patients may also dose at night to avoid the effects, and this appears to be an effective strategy for combating them. Blockade of the H1 receptor may improve pre-existing allergies, pruritus, nausea, and insomnia in afflicted individuals. It may also contribute to weight gain, however. In contrast to the H1 receptor, mirtazapine has only low affinity for the muscarinic acetylcholine receptors, although anticholinergic side effects like dry mouth, constipation, and mydriasis are still sometimes seen in clinical practice.

Pharmacokinetics

The oral bioavailability of mirtazapine is about 50%. It is found mostly bound to plasma proteins, about 85%. It is metabolized primarily in the liver by demethylation and hydroxylation via cytochrome P450 enzymes. One of its major metabolites is desmethylmirtazapine. The overall elimination half-life is 20–40 hours. About 15% is eliminated in feces and 75% in urine.

History

Mirtazapine was first synthesized at Organon and published in 1989, was first approved for use in major depressive disorder in the Netherlands in 1994, and was introduced in the United States in 1996 under the brand name Remeron.

Society and culture

A 15 mg tablet of generic mirtazapine.

Generic names

Mirtazapine is the English and French generic name of the drug and its INN, USAN, USP, BAN, DCF, and JAN.
Its generic name in Spanish is mirtazapina, in German is Mirtazapin, and in Latin is mirtazapinum.
Brand names

Mirtazapine is marketed under many brand names worldwide, including Adco-Mirteron, Afloyan, Amirel, Arintapin Smelt, Avanza, Azapin, Beron, Bilanz, Calixta, Ciblex, Combar, Comenter, Depreram, Divaril, Esprital, Maz, Menelat, Mepirzapine, Merdaten, Meronin, Mi Er Ning, Milivin, Minelza, Minivane, Mirastad, Mirazep, Miro, Miron, Mirrador, Mirt, Mirta, Mirtabene, Mirtadepi, Mirtagamma, Mirtagen, Mirtalan, Mirtamor, Mirtamylan, Mirtan, Mirtaneo, Mirtapax, Mirtapil, Mirtapine, Mirtaron, Mirtastad, Mirtax, Mirtaz, Mirtazap, Mirtazapin, Mirtazapina, Mirtazapine, Mirtazapinum, Mirtazelon, Mirtazon, Mirtazonal, Mirtel, Mirtimash, Mirtin, Mirtine, Mirzapine, Mirzaten, Mirzest, Mitaprex, Mitaxind, Mitocent, Mitrazin, Mizapin, Motofen, Mytra, Norset, Noxibel, Pharmataz, Promyrtil, Ramure, Redepra, Reflex, Remergil, Remergon, Remeron, Remirta, Rexer, Saxib, Sinmaron, Smilon, Tazepin, Tazimed, Tetrazic, Tifona, U-Mirtaron, U-zepine, Valdren, Vastat, Velorin, Yarocen, Zania, Zapex, Zestat, Zismirt, Zispin, Zuleptan, and Zulin.

Chemistry

Mirtazapine is a tetracyclic piperazinoazepine; mianserin was developed by the same team of organic chemists and mirtazapine differs from it via addition of a nitrogen atom in one of the rings. It is a racemic mixture of enantiomers. The (S)-(+)-enantiomer is known as esmirtazapine.
Analogues of mirtazapine include mianserin, setiptiline, and aptazapine.
Synthesis

A chemical synthesis of mirtazapine has been published.
Research

The use of mirtazapine has been explored in several additional conditions:

Sleep apnea/hypopnea
Inappropriate sexual behaviour and other secondary symptoms of autistic spectrum conditions and other pervasive developmental disorders
Antipsychotic-induced akathisia.
Drug withdrawal, dependence and detoxification
Negative, depressive and cognitive symptoms of schizophrenia (as an adjunct)
A case report has been published in which mirtazapine reduced visual hallucinations in a patient with Parkinson's disease psychosis (PDP).[121] This is in alignment with recent findings that inverse agonists at the 5-HT2A receptors are efficacious in attenuating the symptoms of Parkinson's disease psychosis. As is supported by the common practice of prescribing low-dose quetiapine and clozapine for PDP at doses too low to antagonize the D2 receptor, but sufficiently high doses to inversely agonize the 5-HT2A receptors.
Eight case reports have been reported in five papers on the use of mirtazapine in the treatment of hives as of 2017.

Veterinary use

Mirtazapine is sometimes prescribed as an appetite stimulant for cats or dogs experiencing anorexia due to medical conditions such as chronic kidney disease. It is especially useful for treating combined poor appetite and nausea in cats and dogs.

I don't recall you ever mentioning this drug before. I do however remember you recommending Vistaril for hunger stimulation and sleep aid. How do you feel Vistaril compares with Remeron for appetite stimulation?

[Phill]

have you ever heard of anabolex?

Anabolex is an oral drug produced by Ethical Pharma, which is found mainly in pharmacies in the Dominican Republic. Basically, Anabolex is composed of a mixture of 2 parts of Methandrostenolone (Dianabol) and 1 part of Ciproeptadina hydrochloride (Periactin). It is sold in 3mg tablets (2 mg of Dianabol and 1 mg of Periactin).

I don't say anything about the dianabol that we all know.

But Ciproeptadina is a first generation antihistamine drug, also endowed with anticholinergic, antiserotonergic and local anesthetic properties. The drug is used in various dermatological diseases and in the treatment of serotonergic syndrome.
Usually prescribed for allergies, swelling and urticaria or to treat dangerous anaphylactic reactions, its capabilities do not boil down to this.

In fact, Cyproheptadine can also be very useful for those looking to gain weight and quickly add mass thanks to its activity on serotonin inhibition. Therefore, it increases the user's appetite, allowing them to eat more food and do it more often.

D-bol is already known per se as a molecule that increases appetite (like the Boldenone from which it derives), but when combined with Periactin the increase in appetite is much more relevant. Therefore, the use of the drug translates into a much more marked weight gain than that obtained with the use of the single molecule (Methandrostenolone). Obviously, the exponential increase in weight is not to be attributed only to lean mass but also to fat and water.

[Phill]

obviously you can step into a pharmacy and buy only Ciproeptadina hydrochloride (Periactin) and take it with all other steroids.

[Vision]

Witch is your best option to increase the hunger during the off season ?

MK677 ?
GHRP6?
Di Histine?

All the produts you use to increase hunger gives you lethargy and sleepiness , we know because sleepiness is a sign of anabolism .

There's a few drugs and medications out there and most have off label properties for this. Of all drugs, from GHRP"s, some antihistamines and so on..

Here's a medication I used to help with anxiety and depression, I had nbo clue that it had other off label properties that began to show after I took this drug, upon researching it became ne of the best things I just randomly tried that had everything I was looking for.

I have had my bouts with depression here and there and tried medication after medication throughout the years..
Often at times when I have a low my appetite naturally takes a hit as well I would struggle to choke down food all the while trying to have a stable steady keel with my outlook..

A few years ago I introduced a drug that I was kinda unfamiliar with, yet didn't know a whole lot about, after I did some research on it it turned out to be the Swiss army knife of antidepressants and hunger, sleep.

Its role is multi-functional, at the same time not effecting sex drive, libido, ability to climax or anything that SSIR's do to people..

This drug has been amazing not only did it treat my depression symptoms it helped with my sleep much like an ambien would (deep sleep wise).. It has been used to treat people with wasting disorders where they cant eat, or lack of appetite, anorexia..In fact its one of the top 3 most prescribed for treating appetite stimulation.. Dosages will vary.. I started at 30mgs and I was blown away on how well I was sleeping, and the increase and desire to eat was increased to a whole different level sometimes unconformable, it actually became problematic at night.

side effects? zero for me.... maybe a bit groggy upon waking up nothing a dark roast can't fix...

Here's some info below.

Mirtazapine, sold under the brand name Remeron among others, is an atypical antidepressant which is used primarily in the treatment of depression. In addition to its antidepressant properties, mirtazapine has anxiolytic, sedative, antiemetic, and appetite stimulant effects and is sometimes used in the treatment of anxiety disorders, insomnia, nausea and vomiting, and to produce weight gain when desirable. It is taken by mouth.
The drug acts as an antagonist of certain adrenergic and serotonin receptors, and is also a strong antihistamine. It is sometimes described as a noradrenergic and specific serotonergic antidepressant (NaSSA), although the actual evidence in support of this label has been regarded as poor. Chemically, mirtazapine is a tetracyclic antidepressant (TeCA), with four interconnected rings of atoms, and is a relative of the TeCA mianserin(Tolvon).
Mirtazapine was developed by Organon International in the Netherlands and was introduced in the United States in 1996.[4] Its patent expired in 2004, so generic versions are available.

Approved and off-label

Mirtazapine's primary use is the treatment of major depressive disorder and other mood disorders.
However, it has also been found useful in alleviating the following conditions and is sometimes prescribed off-label for their treatment:

Generalized anxiety disorder
Social anxiety disorder
Obsessive–compulsive disorder
Panic disorder
Post-traumatic stress disorder
Low appetite/underweight
Insomnia
Nausea and vomiting
Itching
Headaches and migraine

Effectiveness and tolerability

In 2010 NICE published a guideline for treating depression that included a review of antidepressants. It recommended generic SSRIs as first line choices, as they are "equally effective as other antidepressants and have a favourable risk–benefit ratio." With respect to mirtazapine, it found: "There is no difference between mirtazapine and other antidepressants on any efficacy measure, although in terms of achieving remission mirtazapine appears to have a statistical though not clinical advantage. In addition, mirtazapine has a statistical advantage over SSRIs in terms of reducing symptoms of depression, but the difference is not clinically important. However, there is strong evidence that patients taking mirtazapine are less likely to leave treatment early because of side effects, although this is not the case for patients reporting side effects or leaving treatment early for any reason.
A 2011 Cochrane review that compared mirtazapine to other antidepressants, found that while it appears to have a faster onset in people for whom it works (measured at 2 weeks), it is about the same as other antidepressants at 6 weeks.
A 2012 review focused on antidepressants and sleep found that in many people with sleep disorders caused by depression, mirtazapine reduces the time it takes to fall asleep and increases the quality of sleep, but that in some people it can disturb sleep, causing restless leg syndrome in 8 to 28% of people, and in rare cases causes REM sleep behavior disorder.

A 2018 systematic review and network meta-analysis comparing the efficacy and acceptability of 21 antidepressant drugs showed mirtazapine to be one of the most effective antidepressants in head-to-head studies.

In general, all antidepressants, including mirtazapine, require at least a week for their therapeutic benefits on depressive and anxious symptoms to become apparent.

Side effects

A 2011 Cochrane review found that compared with other antidepressants, it is more likely to cause weight gain and sleepiness, but it is less likely to cause tremor than tricyclic antidepressants, and less likely to cause nausea and sexual dysfunction than SSRIs.
Very common (≥10% incidence) adverse effects include constipation, dry mouth, sleepiness, increased appetite and weight gain.

Common (1–10% incidence) adverse effects include weakness, confusion, dizziness, peripheral edema, and negative lab results like elevated transaminases, elevated serum triglycerides, and elevated total cholesterol.[6]
Mirtazapine is not considered to have a risk of many of the side effects often associated with other antidepressants like the SSRIs, and may actually improve certain ones when taken in conjunction with them. (Those adverse effects include decreased appetite, weight loss, insomnia, nausea and vomiting, diarrhoea, urinary retention, increased body temperature, excessive sweating, pupil dilation and sexual dysfunction.

In general, some antidepressants, especially SSRIs, can paradoxically exacerbate some peoples' depression or anxiety or cause suicidal ideation.[43] Despite its sedating action, mirtazapine is also believed to be capable of this, so in the United States and certain other countries, it carries a black box label warning of these potential effects.
A case report published in 2000 noted an instance in which mirtazapine counteracted the action of clonidine, causing a dangerous rise in blood pressure.

Discontinuation

Mirtazapine and other antidepressants may cause a discontinuation syndrome upon cessation. A gradual and slow reduction in dose is recommended to minimize discontinuation symptoms. Effects of sudden cessation of treatment with mirtazapine may include depression, anxiety, panic attacks, vertigo, restlessness, irritability, decreased appetite, insomnia, diarrhea, nausea, vomiting, flu-like symptoms such as allergies and pruritus, headaches and sometimes hypomania or mania.

Overdose

Mirtazapine is considered to be relatively safe in the event of an overdose, although it is considered slightly more toxic in overdose than most of the SSRIs (except citalopram). Unlike the tricyclic antidepressants, mirtazapine showed no significant cardiovascularadverse effects at 7 to 22 times the maximum recommended dose. Case reports of overdose with as much as 30 to 50 times the standard dose described the drug as relatively nontoxic, compared to tricyclic antidepressants.
Twelve reported fatalities have been attributed to mirtazapine overdose. The fatal toxicity index (deaths per million prescriptions) for mirtazapine is 3.1 (95% CI: 0.1 to 17.2). This is similar to that observed with SSRIs.
Interactions

Concurrent use with inhibitors or inducers of the cytochrome (CYP) P450 isoenzymes CYP1A2, CYP2D6, and/or CYP3A4 can result in altered concentrations of mirtazapine, as these are the main enzymes responsible for its metabolism. As examples, fluoxetine and paroxetine, inhibitors of these enzymes, are known to modestly increase mirtazapine levels, while carbamazepine, an inducer, considerably decreases them. Liver and moderate renal impairment have been reported to decrease the oral clearance of mirtazapine by about 30%; severe renal impairment decreases it by 50%.
According to information from the manufacturers, mirtazapine should not be started within two weeks of any monoamine oxidase inhibitor (MAOI) usage; likewise, MAOIs should not be administered within two weeks of discontinuing mirtazapine.[58] Mirtazapine in combination with an SSRI, SNRI, or TCA as an augmentation strategy is considered to be relatively safe and is often employed therapeutically, with a combination of venlafaxine and mirtazapine, sometimes referred to as "California rocket fuel".

Pharmacology

Values are Ki (nM). The smaller the value, the more strongly the drug binds to the site.
Mirtazapine has antihistamine, α2-blocker, and antiserotonergic activity.[7][67] It is specifically a potent antagonist or inverse agonist of the α2A-, α2B-, and α2C-adrenergic receptors, the serotonin 5-HT2A, 5-HT2C, and 5-HT3receptors, and the histamine H1 receptor.[7][67] Unlike many other antidepressants, it does not inhibit the reuptake of serotonin, norepinephrine, or dopamine, nor does it inhibit monoamine oxidase.[68] Similarly, mirtazapine has weak or no activity as an anticholinergic or blocker of sodium or calcium channels, in contrast to most TCAs. In accordance, it has better tolerability and low toxicity in overdose. As an H1 receptor antagonist, mirtazapine is extremely potent, and is in fact the most potent of all the TCAs and TeCAs. Antagonism of the H1 receptor is by far the strongest activity of mirtazapine, with the drug acting as a selective H1receptor antagonist at low concentrations.
The (S)-(+) enantiomer of mirtazapine is responsible for antagonism of the serotonin 5-HT2A and 5-HT2C receptors,
while the (R)-(–) enantiomer is responsible for antagonism of the 5-HT3 receptor.[11] Both enantiomers are involved in antagonism of the H1 and α2-adrenergic receptors, although the (S)-(+) enantiomer is the stronger antihistamine.

Although not clinically relevant, mirtazapine has been found to act as a partial agonist of the κ-opioid receptor at high concentrations (EC50 = 7.2 μM).
α2-Adrenergic receptor

Antagonism of the α2-adrenergic receptors, which function largely as inhibitory autoreceptors and heteroreceptors, enhances adrenergic and serotonergic neurotransmission, notably central 5-HT1A receptor mediated transmission in the dorsal raphe nucleus and hippocampus; hence, mirtazapine's classification as a NaSSA. Indirect α1 adrenoceptor-mediated enhancement of serotonin cell firing and direct blockade of inhibitory α2heteroreceptors located on serotonin terminals are held responsible for the increase in extracellular serotonin. Because of this, mirtazapine has been said to be a functional "indirect agonist" of the 5-HT1Areceptor. Increased activation of the central 5-HT1A receptor is thought to be a major mediator of efficacy of most antidepressant drugs.

5-HT2 and 5-HT3 receptors

Antagonism of the 5-HT2 subfamily of receptors and inverse agonism of the 5-HT2C receptor appears to be in part responsible for mirtazapine's efficacy in the treatment of depressive states. Mirtazapine increases dopamine release in the prefrontal cortex. Accordingly, it was shown that by blocking the α2-adrenergic receptors and 5-HT2C receptors mirtazapine disinhibited dopamine and norepinephrine activity in these areas in rats.[82] In addition, mirtazapine's antagonism of 5-HT2A receptors has beneficial effects on anxiety, sleep and appetite, as well as sexual function regarding the latter receptor.[7][42] Mirtazapine has been shown to lower drug seeking behaviour in various human and animal studies. It is also being investigated in substance abuse disorders to reduce withdrawal effects and improve remission rates.

Antagonism of the 5-HT3 receptor, an action mirtazapine shares with the approved antiemetic ondansetron, significantly improves pre-existing symptoms of nausea, vomiting, diarrhea, and irritable bowel syndrome in afflicted individuals.[89] Mirtazapine may be used as an inexpensive antiemetic alternative to ondansetron.[24] Blockade of the 5-HT3 receptors has also shown to improve anxiety and to be effective in the treatment of drug addiction in several studies.[90] In conjunction with substance abuse counseling, mirtazapine has been investigated for the purpose of reducing methamphetamine use in dependent individuals with success.[84] In contrast to mirtazapine, the SSRIs, SNRIs, MAOIs, and some TCAs increase the general activity of the 5-HT2A, 5-HT2C, and 5-HT3 receptors leading to a host of negative changes and side effects, the most prominent of which including anorexia, insomnia, sexual dysfunction (loss of libido and anorgasmia), nausea, and diarrhea, among others. As a result, it is often combined with these drugs to reduce their side-effect profile and to produce a stronger antidepressant effect.

Mirtazapine does not have serotonergic activity and does not cause serotonergic side effects or serotonin syndrome.

This is in accordance with the fact that it is not a serotonin reuptake inhibitor or MAOI, nor a serotonin receptor agonist.
There are no reports of serotonin syndrome in association with mirtazapine alone, and mirtazapine has not been found to cause serotonin syndrome in overdose.[9][92][93] However, there are a handful of case reports of serotonin syndrome occurring with mirtazapine in combination with serotonergic drugs like SSRIs, although such reports are unusual, very rare, and do not necessarily implicate mirtazapine as causative.The addition of mirtazapine to an MAOI does not cause serotonin syndrome, and has been considered to be a safe combination.[9][92] Moreover, mirtazapine may actually be useful in the treatment of serotonin syndrome, with at least one publication finding it to be effective in resolving the syndrome. This is in accordance with the fact that the 5-HT2A receptor is the predominant serotonin receptor thought to be involved in the pathophysiology of serotonin syndrome (with the 5-HT1A receptor seeming to be protective). Mirtazapine is a potent 5-HT2A receptor antagonist, and cyproheptadine, a drug that shares this property, mediates recovery from serotonin syndrome and is well-established clinically as an antidote against it.

H1 receptor

Mirtazapine is a very strong H1 receptor inverse agonist and, as a result, it can cause powerful sedative and hypnotic effects.[7] A single 15 mg dose of mirtazapine to healthy volunteers has been found to result in over 80% occupancy of the H1 receptor and to induce intense sleepiness.[72] After a short period of chronic treatment, however, the H1 receptor tends to desensitize and the antihistamine effects become more tolerable. Many patients may also dose at night to avoid the effects, and this appears to be an effective strategy for combating them. Blockade of the H1 receptor may improve pre-existing allergies, pruritus, nausea, and insomnia in afflicted individuals. It may also contribute to weight gain, however. In contrast to the H1 receptor, mirtazapine has only low affinity for the muscarinic acetylcholine receptors, although anticholinergic side effects like dry mouth, constipation, and mydriasis are still sometimes seen in clinical practice.

Pharmacokinetics

The oral bioavailability of mirtazapine is about 50%. It is found mostly bound to plasma proteins, about 85%. It is metabolized primarily in the liver by demethylation and hydroxylation via cytochrome P450 enzymes. One of its major metabolites is desmethylmirtazapine. The overall elimination half-life is 20–40 hours. About 15% is eliminated in feces and 75% in urine.

History

Mirtazapine was first synthesized at Organon and published in 1989, was first approved for use in major depressive disorder in the Netherlands in 1994, and was introduced in the United States in 1996 under the brand name Remeron.

Society and culture

A 15 mg tablet of generic mirtazapine.

Generic names

Mirtazapine is the English and French generic name of the drug and its INN, USAN, USP, BAN, DCF, and JAN.
Its generic name in Spanish is mirtazapina, in German is Mirtazapin, and in Latin is mirtazapinum.
Brand names

Mirtazapine is marketed under many brand names worldwide, including Adco-Mirteron, Afloyan, Amirel, Arintapin Smelt, Avanza, Azapin, Beron, Bilanz, Calixta, Ciblex, Combar, Comenter, Depreram, Divaril, Esprital, Maz, Menelat, Mepirzapine, Merdaten, Meronin, Mi Er Ning, Milivin, Minelza, Minivane, Mirastad, Mirazep, Miro, Miron, Mirrador, Mirt, Mirta, Mirtabene, Mirtadepi, Mirtagamma, Mirtagen, Mirtalan, Mirtamor, Mirtamylan, Mirtan, Mirtaneo, Mirtapax, Mirtapil, Mirtapine, Mirtaron, Mirtastad, Mirtax, Mirtaz, Mirtazap, Mirtazapin, Mirtazapina, Mirtazapine, Mirtazapinum, Mirtazelon, Mirtazon, Mirtazonal, Mirtel, Mirtimash, Mirtin, Mirtine, Mirzapine, Mirzaten, Mirzest, Mitaprex, Mitaxind, Mitocent, Mitrazin, Mizapin, Motofen, Mytra, Norset, Noxibel, Pharmataz, Promyrtil, Ramure, Redepra, Reflex, Remergil, Remergon, Remeron, Remirta, Rexer, Saxib, Sinmaron, Smilon, Tazepin, Tazimed, Tetrazic, Tifona, U-Mirtaron, U-zepine, Valdren, Vastat, Velorin, Yarocen, Zania, Zapex, Zestat, Zismirt, Zispin, Zuleptan, and Zulin.

Chemistry

Mirtazapine is a tetracyclic piperazinoazepine; mianserin was developed by the same team of organic chemists and mirtazapine differs from it via addition of a nitrogen atom in one of the rings. It is a racemic mixture of enantiomers. The (S)-(+)-enantiomer is known as esmirtazapine.
Analogues of mirtazapine include mianserin, setiptiline, and aptazapine.
Synthesis

A chemical synthesis of mirtazapine has been published.
Research

The use of mirtazapine has been explored in several additional conditions:

Sleep apnea/hypopnea
Inappropriate sexual behaviour and other secondary symptoms of autistic spectrum conditions and other pervasive developmental disorders
Antipsychotic-induced akathisia.
Drug withdrawal, dependence and detoxification
Negative, depressive and cognitive symptoms of schizophrenia (as an adjunct)
A case report has been published in which mirtazapine reduced visual hallucinations in a patient with Parkinson's disease psychosis (PDP).[121] This is in alignment with recent findings that inverse agonists at the 5-HT2A receptors are efficacious in attenuating the symptoms of Parkinson's disease psychosis. As is supported by the common practice of prescribing low-dose quetiapine and clozapine for PDP at doses too low to antagonize the D2 receptor, but sufficiently high doses to inversely agonize the 5-HT2A receptors.
Eight case reports have been reported in five papers on the use of mirtazapine in the treatment of hives as of 2017.

Veterinary use

Mirtazapine is sometimes prescribed as an appetite stimulant for cats or dogs experiencing anorexia due to medical conditions such as chronic kidney disease. It is especially useful for treating combined poor appetite and nausea in cats and dogs.

I don't recall you ever mentioning this drug before. I do however remember you recommending Vistaril for hunger stimulation and sleep aid. How do you feel Vistaril compares with Remeron for appetite stimulation?

I actually have this exact thing posted at ASF.. I started this a few summers ago and use it off and on..
I made a thread in the pit and I mentioned it a few other times. Its hardcore, it will make you eat like a beast. it can be trouble at night, like big trouble. you'll eat until your sick.. this drug has put on more Lbs. on people than any other.
Its easy to score from your dr and it is many roles. it truly is used in many cases as a appetite stimulation for many people.
My wifes friend used some from me, just for sleep, and she asked my wife if it made one hungry because her friend said she found herself laying in bed in a zone, stuffing her face and waking up with food. I can't make this up. Her friend was gorging on this stuff, the poor woman just wanted something to help her sleep not gain weight.
I encourage you to ask your dr for some, you'll like what it does. also, I've spoken to many people that also said it helped them out in some of the worst times in their life with depression. Its true, it's great in that dept. no sex sides and it truly helps with depression. its like a great balancing drug. I was on the highest dose at 45mg. if you took that without working your way up, you'd be assed out. 15mg is a great starting dose, I think the next one up from tere was 27.

[Vision]

obviously you can step into a pharmacy and buy only Ciproeptadina hydrochloride (Periactin) and take it with all other steroids.

this is actually controlled and needs a script in many countries, no joke. I just order it online.

[Macedog24]

Mk-677
Eq

[Vision]

Mk-677
Eq

Does MK really help you? I get bloated bad in the gastric region..