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Additional information about the drug Mirtazapine


Mirtazapine, sold under the brand name Remeron among others, is an antidepressant primarily used to treat depression.
Common side effects include increased weight, sleepiness, and dizziness.
Mirtazapine came into medical use in the United States in 1996.
Contents
1 Medical uses
1.1 Effectiveness and tolerability
2 Side effects
2.1 Discontinuation
3 Overdose
4 Interactions
5 Pharmacology
5.1 Pharmacodynamics
5.1.1 α 2 -Adrenergic receptor
5.1.2 5-HT 2 and 5-HT 3 receptors
5.1.3 H 1 receptor
5.2 Pharmacokinetics
5.3 Chemistry
5.4 Synthesis
6 History
7 Society and culture
7.1 Generic names
7.2 Brand names
8 Research
9 Veterinary use
10 References
11 External links
Medical uses
Mirtazapine’s primary use is the treatment of major depressive disorder and other mood disorders.
There is also some tentative evidence 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.”
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, especially at higher doses, causing restless leg syndrome in 8 to 28% of people and in rare cases causes REM sleep behavior disorder.
A 2018 analysis of 21 antidepressants found them to be fairly similar overall.
After one week of usage, mirtazapine was found to have an earlier onset of action compared to SSRIs.
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.
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. )
In general, some antidepressants, especially SSRIs, can paradoxically exacerbate some peoples’ depression or anxiety or cause suicidal ideation.
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.
Overdose
Mirtazapine is considered to be relatively safe in the event of an overdose,
Twelve reported fatalities have been attributed to mirtazapine overdose.
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.
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. ).
Pharmacology
Pharmacodynamics
See also: Pharmacology of antidepressants and Tetracyclic antidepressant § Pharmacology
Mirtazapine
K i (nM)
Species
Ref
SERT
>10,000
Human
NET
≥4,600
Human
DAT
>10,000
Human
5-HT 1A
3,330–5,010
Human
5-HT 1B
3,534–12,600
Human
5-HT 1D
794–5,010
Human
5-HT 1E
728
Human
5-HT 1F
583
Human
5-HT 2A
6.3–69
Human
5-HT 2B
200
Human
5-HT 2C
8.9–39
Human
5-HT 3
7.9
Human
5-HT 4L
>10,000
Human
5-HT 5A
670
Human
5-HT 6
ND
ND
ND
5-HT 7
265
Human
α 1A
316–1,815
Human
α 2A
20
Human
α 2B
88
Human
α 2C
18
Human
β
>10,000
Human
D 1
4,167
Rat
D 2
>5,454
Human
D 3
5,723
Human
D 4
2,518
Human
H 1
0.14–1.6
Human
H 2
>10,000
Rat
H 3
83,200
Human
H 4
>100,000
Human
mACh
670
Human
VGSC
6,905
Rat
VDCC
>10,000
Rat
Values are K i (nM). The smaller the value, the more strongly the drug binds to the site.
Mirtazapine is sometimes described as a noradrenergic and specific serotonergic antidepressant (NaSSA),
Mirtazapine has antihistamine, α 2 -blocker, and antiserotonergic activity.
The ( S )-(+) enantiomer of mirtazapine is responsible for antagonism of the serotonin 5-HT 2A and 5-HT 2C receptors,
Although not clinically relevant, mirtazapine has been found to act as a partial agonist of the κ-opioid receptor at high concentrations ( EC 50 = 7.2 μM).
α 2 -Adrenergic receptor
Antagonism of the α 2 -adrenergic receptors, which function largely as inhibitory autoreceptors and heteroreceptors, enhances adrenergic and serotonergic neurotransmission, notably central 5-HT 1A receptor mediated transmission in the dorsal raphe nucleus and hippocampus ; hence, mirtazapine’s classification as a NaSSA. Indirect α 1 adrenoceptor-mediated enhancement of serotonin cell firing and direct blockade of inhibitory α 2 heteroreceptors located on serotonin terminals are held responsible for the increase in extracellular serotonin.
5-HT 2 and 5-HT 3 receptors
Antagonism of the 5-HT 2 subfamily of receptors and inverse agonism of the 5-HT 2C 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.
Antagonism of the 5-HT 3 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.
Mirtazapine does not have serotonergic activity and does not cause serotonergic side effects or serotonin syndrome.
H 1 receptor
Mirtazapine is a very strong H 1 receptor inverse agonist and, as a result, it can cause powerful sedative and hypnotic effects.
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. : 430
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.
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.
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, Rapizapine, 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.
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).
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.

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