Chemistry:Mirtazapine

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Short description: Antidepressant medication
Mirtazapine
Mirtazapine.svg
Mirtazapine-from-xtal-2003-US-patent-6723845-3D-balls.png
Clinical data
Trade namesRemeron, Mirataz, Avanza, others
Other namesMepirzapine; 6-Azamianserin; ORG-3770[1][2]
AHFS/Drugs.comMonograph
MedlinePlusa697009
License data
Pregnancy
category
Routes of
administration		By mouth (tablets), topical
Drug classNaSSA
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability50%[4][5][6][7]
Protein binding85%[4][5][6][7]
MetabolismLiver (CYP1A2, CYP2D6, CYP3A4)[4][5][6][7][8]
MetabolitesDesmethylmirtazapine (contributes 3–10% of activity)[8][4]
Elimination half-life20–40 hours[4][5][6][7]
ExcretionUrine: 75%[4]
Feces: 15%[4][5][6][7]
Identifiers
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
Chemical and physical data
FormulaC17H19N3
Molar mass265.360 g·mol−1
3D model (JSmol)
ChiralityRacemic mixture
Density1.22 g/cm3
Melting point114 to 116 °C (237 to 241 °F)
Boiling point432 °C (810 °F)
Solubility in waterSoluble in methanol and chloroform mg/mL (20 °C)
  (verify)

Mirtazapine, sold under the brand name Remeron amongst others, is an atypical tetracyclic antidepressant, and as such is used primarily to treat depression.[8][9] Its effects may take up to four weeks, but can also manifest as early as one to two weeks.[9][10] It is often used in cases of depression complicated by anxiety or insomnia.[8][11] The effectiveness of mirtazapine is comparable to other commonly prescribed antidepressants.[12] It is taken by mouth.[9]

Common side effects include sleepiness, dizziness, increased appetite and weight gain.[9] Serious side effects may include mania, low white blood cell count, and increased suicide among children.[9] Withdrawal symptoms may occur with stopping.[13] It is not recommended together with a monoamine oxidase inhibitor,[9] although evidence supporting the danger of this combination has been challenged.[14] It is unclear if use during pregnancy is safe.[9] How it works is not clear, but it may involve blocking certain adrenergic and serotonin receptors.[8][9] Chemically, it is a tetracyclic antidepressant,[9] and is closely related to mianserin. It also has strong antihistaminergic effects.[8][9]

Mirtazapine came into medical use in the United States in 1996.[9] The patent expired in 2004, and generic versions are available.[9][15] In 2020, it was the 104th most commonly prescribed medication in the United States with more than 6 million prescriptions.[16][17]

Medical uses

Mirtazapine is approved by the United States Food and Drug Administration for the treatment of major depressive disorder in adults.[18]

Depression

Mirtazapine is primarily used for major depressive disorder and other mood disorders.[19][20] Onset of action appears faster than some selective serotonin reuptake inhibitors and similar to tricyclic antidepressants.[10][21]

In 2010, the National Institute for Health and Care Excellence recommended generic selective serotonin reuptake inhibitors as first line choices, as they are "equally effective as other antidepressants and have a favourable risk–benefit ratio."[22] 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 selective serotonin reuptake inhibitors in terms of reducing symptoms of depression, but the difference is not clinically significant. 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."[23]

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 two weeks), its efficacy is about the same as other antidepressants after six weeks' use.[10]

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.[24] This seemingly paradoxical dose–response curve of mirtazapine with respect to somnolence is owed to the exceptionally high affinity of the drug for the histamine H1, 5-HT2A, and 5-HT2C receptors; exhibiting near exclusive occupation of these receptors at doses ≤15 mg. However, at higher doses, inverse agonism and constitutive activation of the α2A-, α2B-, and α2C-adrenergic receptors begins to offset activity at H1 receptors leading to decreased somnolence and even a subjective sensation of "activation" in treated patients.[25]

A 2018 analysis of 21 antidepressants found them to be fairly similar overall.[26] It found tentative evidence for mirtazapine being in the more effective group and middle in tolerability.[26]

After one week of usage, mirtazapine was found to have an earlier onset of action compared to selective serotonin reuptake inhibitors.[21][27]

Other

There is also some evidence supporting its use in treating the following conditions, for which it is sometimes prescribed off-label:



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 selective serotonin reuptake inhibitors.[10]

Very common (≥10% incidence) adverse effects include constipation, dry mouth, sleepiness, increased appetite (17%) and weight gain (>7% increase in <50% of children).[5][6][7][42][43][44][45][46][47]

Common (1–10% incidence) adverse effects include weakness, confusion, dizziness, fasciculations (muscle twitches), peripheral edema (swelling, usually of the lower limbs), and negative lab results like elevated transaminases, elevated serum triglycerides, and elevated total cholesterol.[7]

Mirtazapine is not considered to have a risk of many of the side effects often associated with other antidepressants like the selective serotonin reuptake inhibitors, and may actually improve certain ones when taken in conjunction with them.[8][48] (Those adverse effects include decreased appetite, weight loss, insomnia, nausea and vomiting, diarrhea, urinary retention, increased body temperature, excessive sweating, pupil dilation and sexual dysfunction.[8][48])

In general, some antidepressants, especially selective serotonin reuptake inhibitors, can paradoxically exacerbate some peoples' depression or anxiety or cause suicidal ideation.[49] 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, especially for people under the age of 25.[9]

Mirtazapine may induce arthralgia (non-inflammatory joint pain).[50]

A case report published in 2000 noted an instance in which mirtazapine counteracted the action of clonidine, causing a dangerous rise in blood pressure.[51]

In a study comparing 32 antidepressants of all pharmacological classes, mirtazapine was one of the antidepressants most likely to cause nightmare disorder, sleepwalking, restless legs syndrome, night terrors and sleep paralysis.[52]

Mirtazapine has been associated with an increased risk of death compared to other antidepressants in several studies. However, it is more likely that the residual differences between people prescribed mirtazapine rather than a selective serotonin reuptake inhibitor account for the difference in risk of mortality.[53]

In a systematic review of the literature about movement disorders secondary to mirtazapine, fifty-two reports containing 179 cases were assessed. The abnormal movements encountered were restless legs syndrome, tremors, akathisia, periodic limb movement disorder, dystonia, rapid eye movement sleep behavior disorder, dyskinesia, parkinsonism, and tic.[54]

Withdrawal

Mirtazapine and other antidepressants may cause withdrawal symptoms upon cessation.[8][55] A gradual and slow reduction in dose is recommended to minimize withdrawal symptoms.[56] Effects of sudden cessation of treatment with mirtazapine may include depression, anxiety, tinnitus, panic attacks, vertigo, restlessness, irritability, decreased appetite, insomnia, diarrhea, nausea, vomiting, flu-like symptoms, allergy-like symptoms such as pruritus, headaches, and sometimes mania or hypomania.[57][58][59]

Overdose

Mirtazapine is considered to be relatively safe in the event of an overdose,[27] although it is considered slightly more toxic in overdose than most of the selective serotonin reuptake inhibitors (except citalopram).[60] Unlike the tricyclic antidepressants, mirtazapine showed no significant cardiovascular adverse effects at 7 to 22 times the maximum recommended dose.[48]

Twelve reported fatalities have been attributed to mirtazapine overdose.[61][62] The fatal toxicity index (deaths per million prescriptions) for mirtazapine is 3.1 (95% CI: 0.1 to 17.2).[18] This is similar to that observed with selective serotonin reuptake inhibitors.[63][unreliable medical source?]

Interactions

Concurrent use with inhibitors or inducers of the cytochrome P450 isoenzymes CYP1A2, CYP2D6, and/or CYP3A4 can result in altered concentrations of mirtazapine, as these are the main enzymes responsible for its metabolism.[4][8] As examples, fluoxetine and paroxetine, inhibitors of these enzymes, are known to modestly increase mirtazapine levels, while carbamazepine, an inducer, considerably decreases them.[4] Liver impairment and moderate chronic kidney disease have been reported to decrease the oral clearance of mirtazapine by about 30%; severe kidney disease decreases it by 50%.[4]

Mirtazapine in combination with a selective serotonin reuptake inhibitor, serotonin–norepinephrine reuptake inhibitor, or tricyclic antidepressant as an augmentation strategy is considered to be relatively safe and is often employed therapeutically but caution should be given when combined with fluvoxamine. There is a combination of venlafaxine and mirtazapine, sometimes referred to as "California rocket fuel".[64][65] Several case reports document serotonin syndrome induced by the combination of mirtazapine with other agents (olanzapine,[66] quetiapine,[67] tramadol and venlafaxine[68]). Adding fluvoxamine to treatment with mirtazapine may cause a significant increase in mirtazapine concentration. This interaction may necessitate adjustment of the mirtazapine dosage.[69][70]

According to information from the manufacturers, mirtazapine should not be started within two weeks of any monoamine oxidase inhibitor usage; likewise, monoamine oxidase inhibitors should not be administered within two weeks of discontinuing mirtazapine.[9]

The addition of mirtazapine to a monoamine oxidase inhibitor, while potentially having typical or idiosyncratic (unique to the individual) reactions not herein described, does not appear to cause serotonin syndrome.[71] 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).[71][14] Mirtazapine is a potent 5-HT2A receptor antagonist, and cyproheptadine, a medication that shares this property, mediates recovery from serotonin syndrome and is an antidote against it.[14][72]

There is a possible interaction that results in a hypertensive crisis when mirtazapine is given to a patient that has already been on steady doses of clonidine. This involves a subtle consideration, when patients have been on chronic therapy with clonidine and suddenly stop the dosing, a rapid hypertensive rebound sometimes (20%) occurs from increased sympathetic outflow. Clonidine's blood pressure lowering effects are due to stimulation of presynaptic α2 autoreceptors in the CNS which suppress sympathetic outflow. Mirtazapine itself blocks these same α2 autoreceptors, so the effect of adding mirtazapine to a patient stabilized on clonidine may precipitate withdrawal symptoms.[73]

Pharmacology

Pharmacodynamics

Ki (nM) Species Ref
NET 4600+ Human [74][75]
DAT 10000+ Human [75][76]
5-HT1A 3330–5010 Human [8][76]
5-HT1B 3534–12600 Human [8][76]
5-HT1D 794–5,010 Human [8][76]
5-HT1E 728 Human [76]
5-HT1F 583 Human [76]
5-HT2A 6.3–69 Human [8][76]
5-HT2B 200 Human [8]
5-HT2C 8.9–39 Human [8][76]
5-HT3 8.1 Human [77]
5-HT4L 10000+ Human [76]
5-HT5A 670 Human [76]
5-HT6 ND ND ND[76]
5-HT7 265 Human [76]
α1A 1815 Human [76]
α2A 20 Human [76]
α2B 88 Human [76]
α2C 18 Human [76]
β 10000+ Human [76]
D1 4167 Rat
D2 5454+ Human [76]
D3 5,723 Human [76]
D4 2,518 Human [76]
H1 0.14–1.6 Human [78][8][76]
H2 10000+ Rat [79][78]
H3 83200 Human [78]
H4 100000+ Human [78]
VGSC 6905 Rat [76]
VDCC 10000+ Rat [76]
Values are Ki (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),[8] although the actual evidence in support of this label has been regarded as poor.[14] It is a tetracyclic piperazine-azepine.[80]

Mirtazapine is a potent antagonist of 5-HT2A and 5-HT3 receptors. Mirtazapine has no significant affinity for the 5-HT1A and 5-HT1B receptors. Mirtazapine is a potent antagonist of histamine H1 receptors, a property that may explain its prominent sedative effects.[81][82]

Mirtazapine has antihistamine, α2-blocker, and antiserotonergic activity.[8][83] It is specifically a potent antagonist or inverse agonist of the α2A-, α2B-, and α2C-adrenergic receptors, the serotonin 5-HT2A, 5-HT2C, and the histamine H1 receptor.[8][83] Unlike many other antidepressants, it does not inhibit the reuptake of serotonin, norepinephrine, or dopamine,[8][83] nor does it inhibit monoamine oxidase.[84] Similarly, mirtazapine has weak or no activity as an anticholinergic or blocker of sodium or calcium channels, in contrast to most tricyclic antidepressants.[8][76][83] In accordance, it has better tolerability and low toxicity in overdose.[8][85] As an H1 receptor antagonist, mirtazapine is extremely potent, and is in fact the most potent of all the tricyclic and tetracyclic antidepressants.[74][86][87] Antagonism of the H1 receptor is by far the strongest activity of mirtazapine, with the drug acting as a selective H1 receptor antagonist at low concentrations.[8][76]

The (S)-(+) enantiomer of mirtazapine is responsible for antagonism of the serotonin 5-HT2A and 5-HT2C receptors,[88] while the (R)-(–) enantiomer is responsible for antagonism of the 5-HT3 receptor.[88] Both enantiomers are involved in antagonism of the H1 and α2-adrenergic receptors,[6][88] although the (S)-(+) enantiomer is the stronger antihistamine.[89]

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).[90]

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 α2 heteroreceptors located on serotonin terminals are held responsible for the increase in extracellular serotonin.[8][19][91][unreliable medical source?][92][93][unreliable medical source?] Because of this, mirtazapine has been said to be a functional "indirect agonist" of the 5-HT1A receptor.[92] Increased activation of the central 5-HT1A receptor is thought to be a major mediator of efficacy of most antidepressant drugs.[94]

5-HT2 receptor

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.[95][96] Mirtazapine increases dopamine release in the prefrontal cortex.[97][98] 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.[98] 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.[8][48] Mirtazapine has been shown to lower drug seeking behaviour (more specifically to methamphetamine) in various human and animal studies.[99][100][101] It is also being investigated in substance abuse disorders to reduce withdrawal effects and improve remission rates.[99][102][103][104]

Mirtazapine significantly improves pre-existing symptoms of nausea, vomiting, diarrhea, and irritable bowel syndrome in affected individuals.[105] Mirtazapine may be used as an inexpensive antiemetic alternative to Ondansetron.[37] In conjunction with substance abuse counseling, mirtazapine has been investigated for the purpose of reducing methamphetamine use in dependent individuals with success.[100][102][103][104] In contrast to mirtazapine, the selective serotonin reuptake inhibitors, serotonin–norepinephrine reuptake inhibitors, monoamine oxidase inhibitors, and some tricyclic antidepressants 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, nausea, and diarrhea, among others. Its reduced incidence of sexual dysfunction (such as loss of libido and anorgasmia) could be a product of negligible binding to the serotonin transporter (as is generally the cause of sexual dysfunction with most selective serotonin reuptake inhibitors) and antagonism of the 5-HT2A receptors; however, Mirtazapine's high affinity towards and inverse agonism of the 5-HT2C receptors may greatly attenuate those pro-sexual factors (as evidenced by the pro-sexual effects of drugs like m-CPP and Lorcaserin which agonize 5-HT2C receptors in a reasonably selective manner). As a result, it is often combined with these drugs to reduce their side-effect profile and to produce a stronger antidepressant effect.[48][106]

Mirtazapine does not have pro-serotonergic activity and thus does not cause serotonin syndrome.[14][71] This is in accordance with the fact that it is not a serotonin reuptake inhibitor or monoamine oxidase inhibitor, nor a serotonin receptor agonist.[14][71] There are no reports of serotonin syndrome in association with mirtazapine alone, and mirtazapine has not been found to cause serotonin syndrome in overdose.[14][71][107] However, there are a handful of case reports of serotonin syndrome occurring with mirtazapine in combination with serotonergic drugs like selective serotonin reuptake inhibitors, although such reports are very rare, and do not necessarily implicate mirtazapine as causative.[14][108][109][110]

5-HT3 receptor

It is a potent 5-HT3 blocker. It may relieve chemotherapy-related and advanced cancer-related nausea.[37]

H1 receptor

Mirtazapine is a very strong H1 receptor antagonist and, as a result, it can cause powerful sedative and hypnotic effects.[8] 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.[89] 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 affected 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.[111]

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 N-demethylation and hydroxylation via cytochrome P450 enzymes, CYP1A2, CYP2D6, CYP3A4.[112][77] The overall elimination half-life is 20–40 hours, and this is independent of dosage.[4] It is conjugated in the kidney for excretion in the urine, where 75% of the drug is excreted,[113] and about 15% is eliminated in feces.[114]:430 Desmethylmirtazapine is an active metabolite of mirtazapine which is believed to contribute about 3-10% to the drugs overall effects and has a half-life of about 25 hours.[4]

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.[114]:429[115][116] 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. The first step of synthesis is a condensation reaction between the molecule 2-chloro 3-cyanopyridine and the molecule 1-methyl-3-phenylpiperazine.[117]

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.[114]:429[118][119]

Society and culture

A 15 mg tablet of generic mirtazapine.

In the media

Therapeutic levels of mirtazapine were found in the blood of film director Tony Scott during an autopsy after his suicide in 2012.[120]

Generic names

Mirtazapine is the English and French generic name of the drug and its INN, USAN, USP, BAN, DCF, and JAN.[1][2][121] Its generic name in Spanish, Italian and Portuguese is mirtazapina and in German and Swedish is Mirtazapin.[1][2]

Brand names

Mirtazapine is marketed under many brand names worldwide, including Adco-Mirteron, Afloyan, Amirel, Arintapin Smelt, Avanza, Axit, Azapin, Beron, Bilanz, Blumirtax, 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, Mirtor, Mirzapine, Mirzaten, Mirzest, Mitaprex, Mitaxind, Mitocent, Mitrazin, Mizapin, Motofen, Mytra, Norset, Noxibel, Pharmataz, Promyrtil, Rapizapine, Ramure, Razapina, 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.[2]

Research

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

Veterinary use

Mirtazapine also has some veterinary use in cats and dogs. Mirtazapine is sometimes prescribed as an appetite stimulant for cats or dogs experiencing loss of appetite due to medical conditions such as chronic kidney disease. It is especially useful for treating combined poor appetite and nausea in cats and dogs.[133][134][135]

Mirtazapine is indicated for bodyweight gain in cats experiencing poor appetite and weight loss resulting from chronic medical conditions.[136][137]

There are two options for administration: tablets given orally, and an ointment applied topically to the inner surface of the ear.[136][137]

The most common side effects include signs of local irritation or inflammation at the site where the ointment is applied and behavioural changes (increased meowing, hyperactivity, disoriented state or inability to co-ordinate muscle movements, lack of energy/weakness, attention-seeking, and aggression).[136][137]

References

  1. ↑ 1.0 1.1 1.2 Index Nominum 2000: International Drug Directory. Taylor & Francis. 2000. pp. 696–. ISBN 978-3-88763-075-1. https://books.google.com/books?id=5GpcTQD_L2oC&pg=PA696. 
  2. ↑ 2.0 2.1 2.2 2.3 "Mirtazapine - Drugs.com". https://www.drugs.com/international/mirtazapine.html. 
  3. ↑ "Mirtazapine Use During Pregnancy". 23 September 2019. https://www.drugs.com/pregnancy/mirtazapine.html. 
  4. ↑ 4.00 4.01 4.02 4.03 4.04 4.05 4.06 4.07 4.08 4.09 4.10 4.11 "Clinical pharmacokinetics of mirtazapine". Clinical Pharmacokinetics 38 (6): 461–474. June 2000. doi:10.2165/00003088-200038060-00001. PMID 10885584. 
  5. ↑ 5.0 5.1 5.2 5.3 5.4 5.5 "REMERON (mirtazapine) tablet, film coated [Organon Pharmaceuticals USA"]. DailyMed. Organon Pharmaceuticals USA. October 2012. http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=010f9162-9f7f-4b6d-a6e4-4f832f26f38e. 
  6. ↑ 6.0 6.1 6.2 6.3 6.4 6.5 6.6 "Axit Mirtazapine PRODUCT INFORMATION". TGA eBusiness Services. alphapharm. 25 October 2011. https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2010-PI-05345-3. 
  7. ↑ 7.0 7.1 7.2 7.3 7.4 7.5 7.6 "Mirtazapine 30 mg Tablets – Summary of Product Characteristics" (PDF). electronic Medicines Compendium. Sandoz Limited. 20 March 2013. http://www.medicines.org.uk/emc/medicine/25201/SPC/Mirtazapine+30+mg+Tablets/. 
  8. ↑ 8.00 8.01 8.02 8.03 8.04 8.05 8.06 8.07 8.08 8.09 8.10 8.11 8.12 8.13 8.14 8.15 8.16 8.17 8.18 8.19 8.20 8.21 8.22 8.23 8.24 8.25 8.26 8.27 "A review of the pharmacological and clinical profile of mirtazapine". CNS Drug Reviews 7 (3): 249–264. 2001. doi:10.1111/j.1527-3458.2001.tb00198.x. PMID 11607047. 
  9. ↑ 9.00 9.01 9.02 9.03 9.04 9.05 9.06 9.07 9.08 9.09 9.10 9.11 9.12 9.13 "Mirtazapine Monograph for Professionals". American Society of Health-System Pharmacists. https://www.drugs.com/monograph/mirtazapine.html. 
  10. ↑ 10.0 10.1 10.2 10.3 "Mirtazapine versus other antidepressive agents for depression". The Cochrane Database of Systematic Reviews (12): CD006528. December 2011. doi:10.1002/14651858.CD006528.pub2. PMID 22161405. 
  11. ↑ 11.0 11.1 "Tolerability and safety aspects of mirtazapine". Human Psychopharmacology 17 (Suppl 1): S37–S41. June 2002. doi:10.1002/hup.388. PMID 12404669. 
  12. ↑ "[129 Mirtazapine: Update on efficacy, safety, dose response"] (in en-CA). https://www.ti.ubc.ca/2021/05/06/129-mirtazapine-update-on-efficacy-safety-dose-response/. 
  13. ↑ British national formulary : BNF 74 (74 ed.). British Medical Association. 2017. p. 354. ISBN 978-0857112989. 
  14. ↑ 14.0 14.1 14.2 14.3 14.4 14.5 14.6 14.7 "A systematic review of the serotonergic effects of mirtazapine in humans: implications for its dual action status". Human Psychopharmacology 21 (2): 117–125. March 2006. doi:10.1002/hup.750. PMID 16342227. 
  15. ↑ "3". Manual of Clinical Psychopharmacology (7th ed.). Arlington, VA: American Psychiatric Publishing. 2010. ISBN 978-1-58562-377-8. 
  16. ↑ "The Top 300 of 2020". https://clincalc.com/DrugStats/Top300Drugs.aspx. 
  17. ↑ "Mirtazapine - Drug Usage Statistics". https://clincalc.com/DrugStats/Drugs/Mirtazapine. 
  18. ↑ 18.0 18.1 "Mirtazapine". StatPearls. Treasure Island (FL): StatPearls Publishing. 2022. http://www.ncbi.nlm.nih.gov/books/NBK519059/. Retrieved 2022-12-05. 
  19. ↑ 19.0 19.1 "Mirtazapine: clinical overview". The Journal of Clinical Psychiatry 60 (Suppl 17): 9–13; discussion 46–8. 1999. PMID 10446735. 
  20. ↑ "Review of the use of mirtazapine in the treatment of depression". Expert Opinion on Pharmacotherapy 12 (10): 1623–1632. July 2011. doi:10.1517/14656566.2011.585459. PMID 21644844. 
  21. ↑ 21.0 21.1 "Onset of action of antidepressants: results of different analyses". Human Psychopharmacology 17 (Suppl 1): S27–S32. June 2002. doi:10.1002/hup.386. PMID 12404667. 
  22. ↑ "Pharmacological Interventions". Pharmacological Interventions: 10.14. Clinical Practice Recommendations. National Collaborating Centre for Mental Health/British Psychological Society. 2010. https://www.ncbi.nlm.nih.gov/books/NBK63751/#ch10.s159. 
  23. ↑ "Pharmacological Interventions". Pharmacological Interventions: Third-Generation Antidepressants: 10.8.3. Mirtazapine. National Collaborating Centre for Mental Health/British Psychological Society. 2010. https://www.ncbi.nlm.nih.gov/books/NBK63751/#ch10.s68. 
  24. ↑ "Sleep and antidepressant treatment". Current Pharmaceutical Design 18 (36): 5802–5817. 2012. doi:10.2174/138161212803523608. PMID 22681161. 
  25. ↑ "Dose-Dependent Sedating and Stimulating Effects of Mirtazapine". Proceedings of UCLA Healthcare 19. 2015. https://proceedings.med.ucla.edu/wp-content/uploads/2016/11/Dose-Dependent-Sedating-and-Stimulating-Effects-of-Mirtazapine.pdf. 
  26. ↑ 26.0 26.1 "Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis". Lancet 391 (10128): 1357–1366. April 2018. doi:10.1016/S0140-6736(17)32802-7. PMID 29477251. 
  27. ↑ 27.0 27.1 27.2 Maudsley Prescribing Guidelines in Psychiatry (11th ed.). West Sussex: Wiley-Blackwell. 2012. ISBN 978-0-47-097948-8. 
  28. ↑ "Mirtazapine in major depression with comorbid generalized anxiety disorder". The Journal of Clinical Psychiatry 60 (7): 446–448. July 1999. doi:10.4088/JCP.v60n0705. PMID 10453798. 
  29. ↑ "Does anxiety moderate the effectiveness of mirtazapine in patients with treatment-resistant depression? A secondary analysis of the MIR trial". Journal of Psychopharmacology 34 (12): 1342–1349. December 2020. doi:10.1177/0269881120965939. PMID 33143538. 
  30. ↑ 30.0 30.1 30.2 30.3 "Mirtazapine: a review of its use in major depression and other psychiatric disorders". CNS Drugs 23 (5): 427–452. 2009. doi:10.2165/00023210-200923050-00006. PMID 19453203. 
  31. ↑ "[Mirtazapine--an antidepressant]" (in pl). Psychiatria Polska 36 (6 Suppl): 125–130. 2002. PMID 12647431. 
  32. ↑ "Appetite stimulants in cystic fibrosis: a systematic review". Journal of Human Nutrition and Dietetics 20 (6): 526–537. December 2007. doi:10.1111/j.1365-277X.2007.00824.x. PMID 18001374. 
  33. ↑ "Management of symptoms associated with advanced cancer: olanzapine and mirtazapine. A World Health Organization project". Expert Review of Anticancer Therapy 2 (4): 365–376. August 2002. doi:10.1586/14737140.2.4.365. PMID 12647979. 
  34. ↑ "FPIN's clinical inquiries: Antidepressants for the treatment of insomnia in patients with depression". American Family Physician 84 (9): 1–2. November 2011. PMID 22164891. http://www.aafp.org/afp/2011/1101/od1.pdf. 
  35. ↑ "The Effects of Antidepressants on Sleep". Psychiatric Times 29 (6). 13 June 2012. http://www.psychiatrictimes.com/sleep-disorders/effects-antidepressants-sleep. Retrieved 11 July 2017. 
  36. ↑ 36.0 36.1 "Mirtazapine relieves post-electroconvulsive therapy headaches and nausea: a case series and review of the literature". The Journal of ECT 27 (2): 165–167. June 2011. doi:10.1097/YCT.0b013e3181e63346. PMID 21602639. 
  37. ↑ 37.0 37.1 37.2 "Cancer chemotherapy and cachexia: mirtazapine and olanzapine are 5-HT3 antagonists with good antinausea effects". European Journal of Cancer Care 16 (4): 351–354. July 2007. doi:10.1111/j.1365-2354.2006.00760.x. PMID 17587360. 
  38. ↑ "Itch: scratching more than the surface". QJM 96 (1): 7–26. January 2003. doi:10.1093/qjmed/hcg002. PMID 12509645. 
  39. ↑ "Itch in systemic disease: therapeutic options". Dermatologic Therapy 18 (4): 323–327. 2005. doi:10.1111/j.1529-8019.2005.00036.x. PMID 16297004. 
  40. ↑ "Therapy of primary headaches: the role of antidepressants". Neurological Sciences 25 (Suppl 3): S171–S175. October 2004. doi:10.1007/s10072-004-0280-x. PMID 15549531. 
  41. ↑ "[Effects of mirtazapine in patients with chronic tension-type headache. Literature review]" (in hu). Neuropsychopharmacologia Hungarica 8 (2): 67–72. June 2006. PMID 17073214. 
  42. ↑ "mirtazapine (Rx) – Remeron, Remeron SolTab". Medscape. WebMD. http://reference.medscape.com/drug/remeron-soltab-mirtazapine-342966. 
  43. ↑ "Australian Medicines Handbook". Australian Medicines Handbook Pty Ltd. 2013. http://www.amh.net.au. 
  44. ↑ British National Formulary (BNF) (65th ed.). Pharmaceutical Press. 2013. pp. 1120. ISBN 978-0857110848. https://archive.org/details/bnf65britishnati0000unse. 
  45. ↑ "Remeron (Mirtazapine) Drug Information". http://www.rxlist.com/remeron-drug/side-effects-interactions.htm. 
  46. ↑ "Serum lipoproteins improve after successful pharmacologic antidepressant treatment: a randomized open-label prospective trial". The Journal of Clinical Psychiatry 72 (7): 885–891. July 2011. doi:10.4088/JCP.09m05853blu. PMID 21294998. 
  47. ↑ "The effect of antidepressants on lipid homeostasis: a cardiac safety concern?". Expert Opinion on Drug Safety 5 (4): 523–537. July 2006. doi:10.1517/14740338.5.4.523. PMID 16774491. 
  48. ↑ 48.0 48.1 48.2 48.3 48.4 "Review of the results from clinical studies on the efficacy, safety and tolerability of mirtazapine for the treatment of patients with major depression". Journal of Affective Disorders 51 (3): 267–285. December 1998. doi:10.1016/S0165-0327(98)00224-9. PMID 10333982. 
  49. ↑ "Is there evidence for negative effects of antidepressants on suicidality in depressive patients? A systematic review". European Archives of Psychiatry and Clinical Neuroscience 256 (8): 476–496. December 2006. doi:10.1007/s00406-006-0689-8. PMID 17143567. 
  50. ↑ "Mirtazapine-induced arthralgia". British Journal of Clinical Pharmacology 60 (5): 570–572. November 2005. doi:10.1111/j.1365-2125.2005.02481.x. PMID 16236049. 
  51. ↑ "Hypertensive urgency induced by an interaction of mirtazapine and clonidine". Pharmacotherapy 20 (4): 476–478. April 2000. doi:10.1592/phco.20.5.476.35061. PMID 10772378. 
  52. ↑ "Relative frequency of drug-induced sleep disorders for 32 antidepressants in a large set of Internet user reviews". Sleep 44 (12): zsab174. December 2021. doi:10.1093/sleep/zsab174. PMID 34252190. 
  53. ↑ "The risk of all-cause and cause-specific mortality in people prescribed mirtazapine: an active comparator cohort study using electronic health records". BMC Med 20 (1): 43. February 2022. doi:10.1186/s12916-022-02247-x. PMID 35105363. 
  54. ↑ "Mirtazapine-associated movement disorders: A literature review". Tzu Chi Medical Journal 32 (4): 318–330. 2020. doi:10.4103/tcmj.tcmj_13_20. PMID 33163376. 
  55. ↑ "Pharmacology of rapid-onset antidepressant treatment strategies". The Journal of Clinical Psychiatry 62 (Suppl 15): 12–17. 2001. PMID 11444761. 
  56. ↑ "[Withdrawal symptoms of antidepressants]" (in nl). Nederlands Tijdschrift voor Geneeskunde 149 (13): 698–701. March 2005. PMID 15819135. 
  57. ↑ "Panic attacks during discontinuation of mirtazepine". Canadian Journal of Psychiatry 45 (6): 570–571. August 2000. PMID 10986577. 
  58. ↑ "Mirtazapine withdrawal causing hypomania". The British Journal of Psychiatry 175 (4): 390. October 1999. doi:10.1192/bjp.175.4.390a. PMID 10789310. 
  59. ↑ "Switch to mania upon discontinuation of antidepressants in patients with mood disorders: a review of the literature". Canadian Journal of Psychiatry 48 (4): 258–264. May 2003. doi:10.1177/070674370304800410. PMID 12776393. 
  60. ↑ "Suicidal antidepressant overdoses: a comparative analysis by antidepressant type". Journal of Medical Toxicology 4 (4): 238–250. December 2008. doi:10.1007/bf03161207. PMID 19031375. 
  61. ↑ "Death Due to Mirtazapine Overdose". Clinical Toxicology 47 (5): 436–510. 2009. doi:10.1080/15563650902952273. "Abstracts of the XXIX International Congress of the European Association of Poison Centres and Clinical Toxicologists, May 12–15, 2009, Stockholm, Sweden". 
  62. ↑ Disposition of Toxic Drugs and Chemicals in Man (8th ed.). Foster City, CA: Biomedical Publications. 2008. pp. 1045–7. ISBN 978-0-9626523-7-0. 
  63. ↑ "Fatal toxicity of serotoninergic and other antidepressant drugs: analysis of United Kingdom mortality data". BMJ 325 (7376): 1332–1333. December 2002. doi:10.1136/bmj.325.7376.1332. PMID 12468481. 
  64. ↑ Stahl's Essential Psychopharmacology Online: Print and Online. Cambridge, UK: Cambridge University Press. 2008. ISBN 978-0-521-74609-0. http://stahlonline.cambridge.org/prescribers_drug.jsf?page=0521683505c57_p325-330.html.therapeutics&name=Mirtazapine&title=Therapeutics. 
  65. ↑ "California rocket fuel: And what about being a first line treatment?". European Psychiatry 33: S551. March 2016. doi:10.1016/j.eurpsy.2016.01.2033. 
  66. ↑ "Serotonin Syndrome Induced by Combined Use of Mirtazapine and Olanzapine Complicated with Rhabdomyolysis, Acute Renal Failure, and Acute Pulmonary Edema-A Case Report". Acta Neurologica Taiwanica 24 (4): 117–121. December 2015. PMID 27333965. 
  67. ↑ "Severe rhabdomyolysis induced by quetiapine and mirtazapine in a French military soldier". Journal of the Royal Army Medical Corps 164 (2): 127–129. May 2018. doi:10.1136/jramc-2018-000939. PMID 29632134. 
  68. ↑ "Serotonin syndrome resulting from coadministration of tramadol, venlafaxine, and mirtazapine". The Annals of Pharmacotherapy 38 (3): 411–413. March 2004. doi:10.1345/aph.1D344. PMID 14970364. 
  69. ↑ "Fluvoxamine augmentation increases serum mirtazapine concentrations three- to fourfold". The Annals of Pharmacotherapy 35 (10): 1221–1223. October 2001. doi:10.1345/aph.1A014. PMID 11675851. 
  70. ↑ "Fluvoxamine and mirtazapine Interactions" (in en). https://www.drugs.com/drug-interactions/fluvoxamine-with-mirtazapine-1128-0-1640-0.html. 
  71. ↑ 71.0 71.1 71.2 71.3 71.4 "A review of serotonin toxicity data: implications for the mechanisms of antidepressant drug action". Biological Psychiatry 59 (11): 1046–1051. June 2006. doi:10.1016/j.biopsych.2005.11.016. PMID 16460699. 
  72. ↑ "Overview of serotonin syndrome". Annals of Clinical Psychiatry 24 (4): 310–318. November 2012. PMID 23145389. 
  73. ↑ "Interactions Between Mirtazapine and Clonidine". https://www.reliasmedia.com/articles/46173-interaction-between-mirtazapine-and-clonidine. 
  74. ↑ 74.0 74.1 Cite error: Invalid <ref> tag; no text was provided for refs named pmid17471183
  75. ↑ 75.0 75.1 Cite error: Invalid <ref> tag; no text was provided for refs named pmid9537821
  76. ↑ 76.00 76.01 76.02 76.03 76.04 76.05 76.06 76.07 76.08 76.09 76.10 76.11 76.12 76.13 76.14 76.15 76.16 76.17 76.18 76.19 76.20 76.21 76.22 76.23 76.24 "Synthesis and biodistribution of [11C]R107474, a new radiolabeled alpha2-adrenoceptor antagonist". Bioorganic & Medicinal Chemistry 14 (13): 4526–4534. July 2006. doi:10.1016/j.bmc.2006.02.029. PMID 16517171. 
  77. ↑ 77.0 77.1 "A review of the pharmacological and clinical profile of mirtazapine". CNS Drug Reviews 7 (3): 249–264. 2001. doi:10.1111/j.1527-3458.2001.tb00198.x. PMID 11607047. 
  78. ↑ 78.0 78.1 78.2 78.3 "Interactions of recombinant human histamine H1R, H2R, H3R, and H4R receptors with 34 antidepressants and antipsychotics". Naunyn-Schmiedeberg's Archives of Pharmacology 385 (2): 145–170. February 2012. doi:10.1007/s00210-011-0704-0. PMID 22033803. 
  79. ↑ "Neurochemical and autonomic pharmacological profiles of the 6-aza-analogue of mianserin, Org 3770 and its enantiomers". Neuropharmacology 27 (4): 399–408. April 1988. doi:10.1016/0028-3908(88)90149-9. PMID 3419539. 
  80. ↑ "Mirtazapine". https://www.drugbank.ca/drugs/DB00370. 
  81. ↑ "Remeron (mirtazapine)". Food and Drug Administration (FDA). https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020415s030lbl.pdf. 
  82. ↑ "Mirtazapine - an overview | ScienceDirect Topics". https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/mirtazapine. 
  83. ↑ 83.0 83.1 83.2 83.3 "Pharmacology of antidepressants". Journal of Clinical Psychopharmacology 17 (Suppl 1): 2S–18S. April 1997. doi:10.1097/00004714-199704001-00002. PMID 9090573. 
  84. ↑ "Inhibition of monoamine oxidase activity by antidepressants and mood stabilizers". Neuro Endocrinology Letters 31 (5): 645–656. 2010. PMID 21200377. 
  85. ↑ "Pharmacology of antidepressants". Mayo Clinic Proceedings 76 (5): 511–527. May 2001. doi:10.4065/76.5.511. PMID 11357798. 
  86. ↑ Goodman and Gilman's The Pharmacological Basis of Therapeutics, Twelfth Edition. McGraw Hill Professional. 14 January 2011. p. 410. ISBN 978-0-07-176939-6. https://books.google.com/books?id=e_yAOpyyaowC. 
  87. ↑ The American Psychiatric Association Publishing Textbook of Psychopharmacology. American Psychiatric Pub. 10 May 2017. pp. 322–. ISBN 978-1-61537-122-8. https://books.google.com/books?id=v9wnDwAAQBAJ&pg=PA322. 
  88. ↑ 88.0 88.1 88.2 Mirtazapine. The Royal Pharmaceutical Society of Great Britain. 30 January 2013. http://www.medicinescomplete.com/mc/martindale/current/11022-r.htm. Retrieved 3 November 2013. 
  89. ↑ 89.0 89.1 "Histamine H1 receptor occupancy by the new-generation antidepressants fluvoxamine and mirtazapine: a positron emission tomography study in healthy volunteers". Psychopharmacology 230 (2): 227–234. November 2013. doi:10.1007/s00213-013-3146-1. PMID 23728612. 
  90. ↑ "The atypical antidepressant mianserin exhibits agonist activity at κ-opioid receptors". British Journal of Pharmacology 167 (6): 1329–1341. November 2012. doi:10.1111/j.1476-5381.2012.02078.x. PMID 22708686. 
  91. ↑ "The alpha 2-adrenoceptor antagonist Org 3770 enhances serotonin transmission in vivo". European Journal of Pharmacology 253 (1–2): R5–R6. February 1994. doi:10.1016/0014-2999(94)90778-1. PMID 7912194. 
  92. ↑ 92.0 92.1 "Indirect in vivo 5-HT1A-agonistic effects of the new antidepressant mirtazapine". Psychopharmacology 133 (3): 275–282. October 1997. doi:10.1007/s002130050402. PMID 9361334. 
  93. ↑ "Mirtazapine increases dopamine release in prefrontal cortex by 5-HT1A receptor activation". Brain Research Bulletin 63 (3): 237–241. April 2004. doi:10.1016/j.brainresbull.2004.02.007. PMID 15145142. 
  94. ↑ "Putative mechanisms of action of antidepressant drugs in affective and anxiety disorders and pain". Journal of Psychiatry & Neuroscience 26 (1): 37–43. January 2001. PMID 11212592. PMC 1408043. http://www.cma.ca/multimedia/staticContent/HTML/N0/l2/jpn/vol-26/issue-1/pdf/pg37.pdf. Retrieved 20 June 2009. 
  95. ↑ "Serotonin 5-HT2C receptors as a target for the treatment of depressive and anxious states: focus on novel therapeutic strategies". Therapie 60 (5): 441–460. 2005. doi:10.2515/therapie:2005065. PMID 16433010. 
  96. ↑ "Discriminative stimulus properties of the atypical antidepressant, mirtazapine, in rats: a pharmacological characterization". Psychopharmacology 203 (2): 329–341. April 2009. doi:10.1007/s00213-008-1259-8. PMID 18709360. 
  97. ↑ Mirtazapine increases dopamine release in prefrontal cortex by 5-HT1A receptor activation.
  98. ↑ 98.0 98.1 "Mirtazapine enhances frontocortical dopaminergic and corticolimbic adrenergic, but not serotonergic, transmission by blockade of alpha2-adrenergic and serotonin2C receptors: a comparison with citalopram". The European Journal of Neuroscience 12 (3): 1079–1095. March 2000. doi:10.1046/j.1460-9568.2000.00982.x. PMID 10762339. 
  99. ↑ 99.0 99.1 "SB 206553, a putative 5-HT2C inverse agonist, attenuates methamphetamine-seeking in rats". BMC Neuroscience 13 (1): 65. June 2012. doi:10.1186/1471-2202-13-65. PMID 22697313. 
  100. ↑ 100.0 100.1 "Mirtazapine to reduce methamphetamine use: a randomized controlled trial". Archives of General Psychiatry 68 (11): 1168–1175. November 2011. doi:10.1001/archgenpsychiatry.2011.124. PMID 22065532. 
  101. ↑ "Mirtazapine treatment after conditioning with methamphetamine alters subsequent expression of place preference". Drug and Alcohol Dependence 99 (1–3): 231–239. January 2009. doi:10.1016/j.drugalcdep.2008.08.005. PMID 18945553. 
  102. ↑ 102.0 102.1 "Pharmacotherapy for methamphetamine dependence: a review of the pathophysiology of methamphetamine addiction and the theoretical basis and efficacy of pharmacotherapeutic interventions". Annals of Clinical Psychiatry 20 (3): 145–155. 2008. doi:10.1080/10401230802177656. PMID 18633741. 
  103. ↑ 103.0 103.1 "Treatments for methamphetamine abuse: a literature review for the clinician". Journal of Pharmacy Practice 24 (6): 541–550. December 2011. doi:10.1177/0897190011426557. PMID 22095579. 
  104. ↑ 104.0 104.1 "Pharmacotherapy of amphetamine-type stimulant dependence: an update". Drug and Alcohol Review 32 (5): 449–460. September 2013. doi:10.1111/dar.12048. PMID 23617468. 
  105. ↑ "Mirtazapine may be useful in treating nausea and insomnia of cancer chemotherapy". Supportive Care in Cancer 9 (6): 469–470. September 2001. doi:10.1007/s005200000215. PMID 11585276. 
  106. ↑ "Mirtazapine for treatment of nausea induced by selective serotonin reuptake inhibitors". Canadian Journal of Psychiatry 49 (10): 707. October 2004. doi:10.1177/070674370404901014. PMID 15560319. 
  107. ↑ "Mirtazapine overdose is unlikely to cause major toxicity". Clinical Toxicology 52 (1): 20–24. January 2014. doi:10.3109/15563650.2013.859264. PMID 24228948. 
  108. ↑ "[Serotonin syndrome after administration of mirtazapine in a critical care unit]" (in es). Revista Espanola de Anestesiologia y Reanimacion 56 (8): 515–516. October 2009. doi:10.1016/s0034-9356(09)70444-x. PMID 19994622. 
  109. ↑ "Sertraline-induced serotonin syndrome followed by mirtazapine reaction". Progress in Neuro-Psychopharmacology & Biological Psychiatry 34 (6): 1128–1129. August 2010. doi:10.1016/j.pnpbp.2010.04.015. PMID 20430060. 
  110. ↑ "A venlafaxine and mirtazapine-induced serotonin syndrome confirmed by de- and re-challenge". International Journal of Clinical Pharmacy 34 (5): 686–688. October 2012. doi:10.1007/s11096-012-9666-7. PMID 22752315. 
  111. ↑ "Mirtazapine: clinical advantages in the treatment of depression". Journal of Clinical Psychopharmacology 17 (Suppl 1): 34S–39S. April 1997. doi:10.1097/00004714-199704001-00005. PMID 9090576. 
  112. ↑ "High-Throughput Metabolic Soft-Spot Identification in Liver Microsomes by LC/UV/MS: Application of a Single Variable Incubation Time Approach". Molecules 27 (22): 8058. November 2022. doi:10.3390/molecules27228058. PMID 36432161. 
  113. ↑ Mirtazapine. Profiles of Drug Substances, Excipients and Related Methodology. 43. 1 January 2018. pp. 209–254. doi:10.1016/bs.podrm.2018.01.002. ISBN 9780128151259. 
  114. ↑ 114.0 114.1 114.2 "Chapter 21: Mirtazapine". The American Psychiatric Publishing Textbook of Psychopharmacology (4th ed.). Washington, D.C.: American Psychiatric Pub.. 2009. ISBN 9781585623099. 
  115. ↑ "Mirtazapine label – Australia". GuildLink, a wholly owned subsidiary company of the Pharmacy Guild of Australia.. 27 May 2016. http://secure.healthlinks.net.au/content/msd/pi.cfm?product=mkpavant. 
  116. ↑ "A comparison of the physicochemical and biological properties of mirtazapine and mianserin". The Journal of Pharmacy and Pharmacology 49 (4): 403–411. April 1997. doi:10.1111/j.2042-7158.1997.tb06814.x. PMID 9232538. 
  117. ↑ "Improved Synthesis of Mirtazapine". Organic Preparations and Procedures International 39 (4): 399–402. 2007. doi:10.1080/00304940709458595. 
  118. ↑ "The synthesis of org 3770 labelled with 3H, 13C AND 14C". Journal of Labelled Compounds and Radiopharmaceuticals 27 (9): 1055–1068. September 1989. doi:10.1002/jlcr.2580270911. 
  119. ↑ "Remeron New FDA Drug Approvalh". http://www.centerwatch.com/drug-information/fda-approved-drugs/drug/135/remeron-mirtazapine. 
  120. ↑ "Antidepressant, Sleep Aid Found in Director Tony Scott's Body". 22 October 2012. http://www.thedailybeast.com/articles/2012/10/22/anti-depressant-sleep-aid-found-in-director-tony-scott-s-body.html. 
  121. ↑ Concise Dictionary of Pharmacological Agents: Properties and Synonyms. Springer Science & Business Media. 6 December 2012. p. 183. ISBN 978-94-011-4439-1. https://books.google.com/books?id=tsjrCAAAQBAJ&pg=PA183. 
  122. ↑ "Pharmacological approaches to the treatment of obstructive sleep apnoea". Expert Opinion on Investigational Drugs 18 (5): 647–656. May 2009. doi:10.1517/13543780902877674. PMID 19388881. https://www.zora.uzh.ch/id/eprint/28318/1/28318_manuscript.pdf. Retrieved 23 December 2021. 
  123. ↑ "Two randomized placebo-controlled trials to evaluate the efficacy and tolerability of mirtazapine for the treatment of obstructive sleep apnea". Sleep 31 (6): 824–831. June 2008. doi:10.1093/sleep/31.6.824. PMID 18548827. 
  124. ↑ "Pharmacotherapy of pervasive developmental disorders in children and adolescents". CNS Drugs 18 (14): 1031–1052. 2004. doi:10.2165/00023210-200418140-00006. PMID 15584771. 
  125. ↑ "Synergistic action of 5-HT2A antagonists and selective serotonin reuptake inhibitors in neuropsychiatric disorders". Neuropsychopharmacology 28 (2): 402–412. February 2003. doi:10.1038/sj.npp.1300057. PMID 12589395. 
  126. ↑ "Akathisia and second-generation antipsychotic drugs". Current Opinion in Psychiatry 22 (3): 293–299. May 2009. doi:10.1097/YCO.0b013e32832a16da. PMID 19378382. 
  127. ↑ "Role of mirtazapine in the treatment of antipsychotic-induced akathisia". The Annals of Pharmacotherapy 42 (6): 841–846. June 2008. doi:10.1345/aph.1K672. PMID 18460588. 
  128. ↑ "Mirtazapine, and mirtazapine-like compounds as possible pharmacotherapy for substance abuse disorders: evidence from the bench and the bedside". Pharmacology & Therapeutics 136 (3): 343–353. December 2012. doi:10.1016/j.pharmthera.2012.08.013. PMID 22960395. 
  129. ↑ Polypharmacy in Psychiatry Practice, Volume I. Springer Science+Business Media Dordrecht. 2013. doi:10.1007/978-94-007-5805-6. ISBN 9789400758056. 
  130. ↑ "Meta-Analysis of Efficacy of Mirtazapine as an Adjunctive Treatment of Negative Symptoms in Schizophrenia". Clinical Schizophrenia & Related Psychoses 9 (2): 88–95. Jul 2015. doi:10.3371/CSRP.VIRE.030813. PMID 23491969. 
  131. ↑ "Mirtazapine improves visual hallucinations in Parkinson's disease: a case report". Psychogeriatrics 13 (2): 103–107. June 2013. doi:10.1111/j.1479-8301.2012.00432.x. PMID 23909968. 
  132. ↑ "Antidepressants have Anti-inflammatory Effects that may be Relevant to Dermatology: A Systematic Review". Acta Dermato-Venereologica 97 (8): 897–905. August 2017. doi:10.2340/00015555-2702. PMID 28512664. 
  133. ↑ "Remeron for Cats". http://www.vetinfo.com/remeron-for-cats.html. 
  134. ↑ Mirtazapine (Remeron). 8 August 2017. http://www.veterinarypartner.com/Content.plx?P=A&A=2552. 
  135. ↑ "Pharmacological appetite stimulation: rational choices in the inappetent cat". Journal of Feline Medicine and Surgery 16 (9): 749–756. September 2014. doi:10.1177/1098612X14545273. PMID 25146662. 
  136. ↑ 136.0 136.1 136.2 "Mirataz EPAR". 11 October 2019. https://www.ema.europa.eu/en/medicines/veterinary/EPAR/mirataz.  Text was copied from this source, which is copyright European Medicines Agency, 2020. Reproduction is authorised provided the source is acknowledged.
  137. ↑ 137.0 137.1 137.2 "Mirataz- mirtazapine ointment". 8 May 2020. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f4a55914-6b6e-4e81-a84c-3999aa7bd79e. 

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