Mirtazapine

{{Short description|Antidepressant medication}} {{Use dmy dates|date=February 2024}} {{cs1 config|name-list-style=vanc|display-authors=6}} {{Infobox drug | Verifiedfields = verified | Watchedfields = verified | verifiedrevid = 408610027 | image = Mirtazapine enantiomers labelled.svg | image_class = skin-invert-image | width = 250px | alt = | image2 = Mirtazapine enantiomers ball-and-stick models from xtal 2011.png | image_class2 = bg-transparent | width2 = 250px

<!-- Clinical data --> | tradename = Remeron, others | Drugs.com = {{drugs.com|monograph|mirtazapine}} | MedlinePlus = a697009 | DailyMedID = Mirtazapine | pregnancy_AU = B3 | pregnancy_AU_comment = <ref name="Drugs.com pregnancy">{{cite web | title=Mirtazapine Use During Pregnancy | website=Drugs.com | date=23 September 2019 | url=https://www.drugs.com/pregnancy/mirtazapine.html | access-date=4 March 2020 | archive-date=22 August 2020 | archive-url=https://web.archive.org/web/20200822200226/https://www.drugs.com/pregnancy/mirtazapine.html | url-status=live }}</ref> | routes_of_administration = By mouth, topical | class = Noradrenergic and specific serotonergic antidepressant (NaSSA) | ATC_prefix = N06 | ATC_suffix = AX11 | ATC_supplemental = | legal_AU = S4 | legal_BR = C1 | legal_BR_comment = <ref>{{Cite web |author=Anvisa |author-link=Brazilian Health Regulatory Agency |date=31 March 2023 |title=RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial |trans-title=Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control|url=https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |url-status=live |archive-url=https://web.archive.org/web/20230803143925/https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |archive-date=3 August 2023 |access-date=16 August 2023 |publisher=Diário Oficial da União |language=pt-BR |publication-date=4 April 2023}}</ref> | legal_CA = Rx-only | legal_UK = POM | legal_US = Rx-only | legal_US_comment = <ref name="Remeron FDA label">{{cite web | title=Remeron- mirtazapine tablet, film coated; Remeronsoltab- mirtazapine tablet, orally disintegrating | website=DailyMed | date=4 March 2024 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=98ad1917-a094-44f5-a28f-a64a8cfcd887 | access-date=1 September 2024}}</ref><ref>{{cite web | title=Mirataz- mirtazapine ointment | website=DailyMed | date=5 April 2024 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5ff9fdb7-554f-4f91-8cfc-6d05094384c6 | access-date=1 September 2024}}</ref> | legal_EU = Rx-only

<!-- Pharmacokinetic data --> | bioavailability = 50%<ref name="pmid10885584"/><ref name = "Remeron FDA label" /><ref name = AXIT/><ref name = EMC/> | protein_bound = 85%<ref name="pmid10885584" /><ref name="Remeron FDA label" /><ref name = AXIT/><ref name = EMC/> | metabolism = Liver (CYP1A2, CYP2D6, CYP3A4)<ref name="pmid10885584" /><ref name = "Remeron FDA label" /><ref name = AXIT/><ref name = EMC/><ref name=Ant2001 /> | metabolites = Desmethylmirtazapine (contributes 3–10% of activity)<ref name=Ant2001 /><ref name="pmid10885584" >{{cite journal | vauthors = Timmer CJ, Sitsen JM, Delbressine LP | title = Clinical pharmacokinetics of mirtazapine | journal = Clinical Pharmacokinetics | volume = 38 | issue = 6 | pages = 461–474 | date = June 2000 | pmid = 10885584 | doi = 10.2165/00003088-200038060-00001 | s2cid = 27697181 }}</ref> | elimination_half-life = 20–40 hours<ref name="pmid10885584" /><ref name = "Remeron FDA label" /><ref name = AXIT/><ref name = EMC/> | excretion = Urine: 75%<ref name="pmid10885584" /><br />Feces: 15%<ref name="pmid10885584" /><ref name = "Remeron FDA label" /><ref name = AXIT/><ref name = EMC/>

<!-- Identifiers --> | IUPHAR_ligand = 7241 | CAS_number_Ref = {{cascite|correct|CAS}} | CAS_number = 85650-52-8 | PubChem = 4205 | DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank = DB00370 | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 4060 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = A051Q2099Q | KEGG_Ref = {{keggcite|correct|kegg}} | KEGG = D00563 | ChEBI_Ref = {{ebicite|correct|EBI}} | ChEBI = 6950 | ChEMBL_Ref = {{ebicite|correct|EBI}} | ChEMBL = 654 | synonyms = Mepirzapine; 6-Azamianserin; ORG-3770<ref name="IndexNominum2000" /><ref name="Drugs.com" />

<!-- Chemical data --> | IUPAC_name = (±)-5-methyl-2,5,19-triazatetracyclo[13.4.0.02,7.08,13]nonadeca-1(15),8,10,12,16,18-hexaene | C = 17 | H = 19 | N = 3 | SMILES = n1cccc3c1N4C(c2ccccc2C3)CN(C)CC4 | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI = 1S/C17H19N3/c1-19-9-10-20-16(12-19)15-7-3-2-5-13(15)11-14-6-4-8-18-17(14)20/h2-8,16H,9-12H2,1H3 | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey = RONZAEMNMFQXRA-UHFFFAOYSA-N | chirality = Racemic mixture | density = 1.22 | melting_point = 114 | melting_high = 116 | boiling_point = 432 | solubility = Soluble in methanol and chloroform }}

{{redir-dist|Azapin|azepine}}

<!-- Definition and medical uses --> '''Mirtazapine''', sold under the brand name '''Remeron''' among others, is an atypical tetracyclic antidepressant, and as such is used primarily to treat depression.<ref name=Ant2001/><ref name=AHSF2018>{{cite web |title=Mirtazapine Monograph for Professionals |url=https://www.drugs.com/monograph/mirtazapine.html |website=Drugs.com |publisher=American Society of Health-System Pharmacists |access-date=20 November 2018 |archive-date=10 January 2021 |archive-url=https://web.archive.org/web/20210110231757/https://www.drugs.com/monograph/mirtazapine.html |url-status=live }}</ref> Its effects may take up to four weeks but can also manifest as early as one to two weeks.<ref name=AHSF2018/><ref name=Cochrane2011/> It is often used in cases of depression complicated by anxiety or insomnia.<ref name=Ant2001/><ref name=Nut2002>{{cite journal | vauthors = Nutt DJ | title = Tolerability and safety aspects of mirtazapine | journal = Human Psychopharmacology | volume = 17 | issue = Suppl 1 | pages = S37–S41 | date = June 2002 | pmid = 12404669 | doi = 10.1002/hup.388 | s2cid = 23699759 }}</ref> The effectiveness of mirtazapine is comparable to other commonly prescribed antidepressants.<ref name=TI2021>{{cite web |title=[129] Mirtazapine: Update on efficacy, safety, dose response |url=https://www.ti.ubc.ca/2021/05/06/129-mirtazapine-update-on-efficacy-safety-dose-response/ |website=www.ti.ubc.ca |access-date=8 May 2021 |archive-date=7 May 2021 |archive-url=https://web.archive.org/web/20210507191909/https://www.ti.ubc.ca/2021/05/06/129-mirtazapine-update-on-efficacy-safety-dose-response/ |url-status=live }}</ref> It is taken by mouth.<ref name=AHSF2018/>

<!-- Side effects and mechanism --> Common side effects include sleepiness, dizziness, increased appetite, and weight gain.<ref name="AHSF2018" /> Serious side effects may include mania, low white blood cell count, and increased suicide among children.<ref name="AHSF2018" /> Withdrawal symptoms may occur when stopping.<ref name="BNF74">{{cite book|title=British national formulary: BNF 74|date=2017|publisher=British Medical Association|isbn=978-0-85711-298-9|page=354|edition=74th }}</ref> It is not recommended together with a monoamine oxidase inhibitor,<ref name="AHSF2018" /> although evidence supporting the danger of this combination has been challenged.<ref name="pmid16342227" /> It is unclear if use during pregnancy is safe.<ref name="AHSF2018" /> How it works is not clear, but it may involve blocking certain adrenergic and serotonin receptors.<ref name=Ant2001/><ref name=AHSF2018/> Chemically, it is a tetracyclic antidepressant,<ref name=AHSF2018/> and is closely related to mianserin. It also has strong antihistaminergic effects.<ref name=Ant2001>{{cite journal | vauthors = Anttila SA, Leinonen EV | title = A review of the pharmacological and clinical profile of mirtazapine | journal = CNS Drug Reviews | volume = 7 | issue = 3 | pages = 249–264 | year = 2001 | pmid = 11607047 | pmc = 6494141 | doi = 10.1111/j.1527-3458.2001.tb00198.x }}</ref><ref name=AHSF2018/>

<!-- History and culture --> Mirtazapine came into medical use in the United States in 1996.<ref name=AHSF2018/> The patent expired in 2004, and generic versions are available.<ref name=AHSF2018/><ref>{{cite book | vauthors = Schatzberg AF, Cole JO, DeBattista C | title = Manual of Clinical Psychopharmacology | edition = 7th | date= 2010| publisher = American Psychiatric Publishing | location = Arlington, VA | isbn = 978-1-58562-377-8 | chapter = 3 }}</ref> In 2023, it was the 99th most commonly prescribed medication in the United States, with more than 6{{nbsp}}million prescriptions.<ref name="Top300Drugs">{{cite web | title=Top 300 of 2023 | url=https://clincalc.com/DrugStats/Top300Drugs.aspx | website=ClinCalc | access-date=12 August 2025 | archive-date=12 August 2025 | archive-url=https://web.archive.org/web/20250812130026/https://clincalc.com/DrugStats/Top300Drugs.aspx | url-status=live }}</ref><ref>{{cite web | title = Mirtazapine Drug Usage Statistics, United States, 2014 - 2023 | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/Mirtazapine | access-date = 18 August 2025 }}</ref> {{TOC limit}}

==Medical uses== Mirtazapine is approved by the United States Food and Drug Administration for the treatment of major depressive disorder in adults.<ref name=":0">{{cite book |vauthors=Jilani TN, Gibbons JR, Faizy RM, Saadabadi A |chapter=Mirtazapine |date=2022 |chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK519059/ |title=StatPearls |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=30085601 |access-date=5 December 2022 |archive-date=12 December 2022 |archive-url=https://web.archive.org/web/20221212213412/https://www.ncbi.nlm.nih.gov/books/NBK519059/ |url-status=live }}</ref>

===Depression=== Mirtazapine is primarily used for major depressive disorder and other mood disorders.<ref name="pmid10446735">{{cite journal | vauthors = Gorman JM | title = Mirtazapine: clinical overview | journal = The Journal of Clinical Psychiatry | volume = 60 | issue = Suppl 17 | pages = 9–13; discussion 46–8 | year = 1999 | pmid = 10446735 }}</ref><ref name="pmid21644844">{{cite journal | vauthors = Benjamin S, Doraiswamy PM | title = Review of the use of mirtazapine in the treatment of depression | journal = Expert Opinion on Pharmacotherapy | volume = 12 | issue = 10 | pages = 1623–1632 | date = July 2011 | pmid = 21644844 | doi = 10.1517/14656566.2011.585459 | s2cid = 10212539 }}</ref> Onset of action appears faster than some selective serotonin reuptake inhibitors and similar to tricyclic antidepressants.<ref name=Cochrane2011/><ref name="pmid12404667" />

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."<ref>{{cite book|title=Pharmacological Interventions: 10.14. Clinical Practice Recommendations|chapter=Pharmacological Interventions|date=2010|publisher=National Collaborating Centre for Mental Health/British Psychological Society|url=https://www.ncbi.nlm.nih.gov/books/NBK63751/#ch10.s159|access-date=22 July 2017|archive-date=6 September 2020|archive-url=https://web.archive.org/web/20200906074156/https://www.ncbi.nlm.nih.gov/books/NBK63751/#ch10.s159|url-status=live}}</ref> For mirtazapine, it found "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."<ref>{{cite book|title=Pharmacological Interventions: Third-Generation Antidepressants: 10.8.3. Mirtazapine|chapter=Pharmacological Interventions|date=2010|publisher=National Collaborating Centre for Mental Health/British Psychological Society|url=https://www.ncbi.nlm.nih.gov/books/NBK63751/#ch10.s68|access-date=22 July 2017|archive-date=6 September 2020|archive-url=https://web.archive.org/web/20200906074156/https://www.ncbi.nlm.nih.gov/books/NBK63751/#ch10.s68|url-status=live}}</ref>

A 2011 Cochrane review comparing mirtazapine to other antidepressants found that while it appeared to have a faster onset in people for whom it worked (measured at two weeks), its efficacy was about the same as other antidepressants after six weeks' use.<ref name=Cochrane2011>{{cite journal | vauthors = Watanabe N, Omori IM, Nakagawa A, Cipriani A, Barbui C, Churchill R, Furukawa TA | title = Mirtazapine versus other antidepressive agents for depression | journal = The Cochrane Database of Systematic Reviews | issue = 12 | article-number = CD006528 | date = December 2011 | pmid = 22161405 | pmc = 4158430 | doi = 10.1002/14651858.CD006528.pub2 }}</ref>

A 2012 review focused on antidepressants and sleep found that mirtazapine reduced the time it took to fall asleep and improved the quality of sleep in many people with sleep disorders caused by depression, but that it could also disturb sleep in many people, especially at higher doses, causing restless leg syndrome in 8 to 28% of people and in rare cases causes REM sleep behavior disorder.<ref>{{cite journal | vauthors = Wichniak A, Wierzbicka A, Jernajczyk W | title = Sleep and antidepressant treatment | journal = Current Pharmaceutical Design | volume = 18 | issue = 36 | pages = 5802–5817 | date = 2012 | pmid = 22681161 | doi = 10.2174/138161212803523608 }}</ref> 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-HT_2A, and 5-HT_2C receptors; exhibiting near exclusive occupation of these receptors at doses ≤15&nbsp;mg. However, at higher doses, inverse agonism and constitutive activation of the α_2A-, α_2B-, and α_2C-adrenergic receptors begins to offset activity at H₁ receptors leading to decreased somnolence and even a subjective sensation of "activation" in treated patients.<ref>{{Cite journal|vauthors=Leonard S|date=2015|title=Dose-Dependent Sedating and Stimulating Effects of Mirtazapine|url=https://proceedings.med.ucla.edu/wp-content/uploads/2016/11/Dose-Dependent-Sedating-and-Stimulating-Effects-of-Mirtazapine.pdf|journal=Proceedings of UCLA Healthcare|volume=19|access-date=27 August 2021|archive-date=23 September 2021|archive-url=https://web.archive.org/web/20210923115736/https://www.proceedings.med.ucla.edu/wp-content/uploads/2016/11/Dose-Dependent-Sedating-and-Stimulating-Effects-of-Mirtazapine.pdf|url-status=live}}</ref>

A 2018 analysis of 21 antidepressants found them to be fairly similar overall.<ref name=Cip2018/> It found tentative evidence for mirtazapine being in the more effective group and middle in tolerability.<ref name=Cip2018>{{cite journal | vauthors = Cipriani A, Furukawa TA, Salanti G, Chaimani A, Atkinson LZ, Ogawa Y, Leucht S, Ruhe HG, Turner EH, Higgins JP, Egger M, Takeshima N, Hayasaka Y, Imai H, Shinohara K, Tajika A, Ioannidis JP, Geddes JR | title = 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 | journal = Lancet | volume = 391 | issue = 10128 | pages = 1357–1366 | date = April 2018 | pmid = 29477251 | pmc = 5889788 | doi = 10.1016/S0140-6736(17)32802-7 }}</ref>

After one week of usage, mirtazapine was found to have an earlier onset of action compared to selective serotonin reuptake inhibitors.<ref name="pmid12404667">{{cite journal | vauthors = Thompson C | title = Onset of action of antidepressants: results of different analyses | journal = Human Psychopharmacology | volume = 17 | issue = Suppl 1 | pages = S27–S32 | date = June 2002 | pmid = 12404667 | doi = 10.1002/hup.386 | s2cid = 45925573 | doi-access = free }}</ref><ref name="Maudsley">{{cite book | isbn = 978-0-47-097948-8 | title = Maudsley Prescribing Guidelines in Psychiatry | edition = 11th | vauthors = Taylor D, Paton C, Shitij K | date = 2012 | publisher = Wiley-Blackwell | location = West Sussex }} </ref>

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

{{div col|colwidth=30em}} * Generalized anxiety disorder<ref name=Ant2001 /><ref name="pmid10453798">{{cite journal | vauthors = Goodnick PJ, Puig A, DeVane CL, Freund BV | title = Mirtazapine in major depression with comorbid generalized anxiety disorder | journal = The Journal of Clinical Psychiatry | volume = 60 | issue = 7 | pages = 446–448 | date = July 1999 | pmid = 10453798 | doi = 10.4088/JCP.v60n0705 }}</ref><ref>{{cite journal | vauthors = Rifkin-Zybutz R, MacNeill S, Davies SJ, Dickens C, Campbell J, Anderson IM, Chew-Graham CA, Peters TJ, Lewis G, Wiles N, Kessler D | title = Does anxiety moderate the effectiveness of mirtazapine in patients with treatment-resistant depression? A secondary analysis of the MIR trial | journal = Journal of Psychopharmacology | volume = 34 | issue = 12 | pages = 1342–1349 | date = December 2020 | pmid = 33143538 | pmc = 7708671 | doi = 10.1177/0269881120965939 | doi-access = free }}</ref> * Social anxiety disorder<ref name="pmid19453203">{{cite journal | vauthors = Croom KF, Perry CM, Plosker GL | title = Mirtazapine: a review of its use in major depression and other psychiatric disorders | journal = CNS Drugs | volume = 23 | issue = 5 | pages = 427–452 | year = 2009 | pmid = 19453203 | doi = 10.2165/00023210-200923050-00006 | s2cid = 41694941 }}</ref> * Obsessive–compulsive disorder<ref name="pmid19453203" /> * Panic disorder<ref name="pmid19453203" /> * Post-traumatic stress disorder<ref name="pmid19453203" /> * Low appetite/underweight<ref name="pmid12647431">{{cite journal | vauthors = Landowski J | title = [Mirtazapine--an antidepressant] | language = pl | journal = Psychiatria Polska | volume = 36 | issue = 6 Suppl | pages = 125–130 | year = 2002 | pmid = 12647431 }}</ref><ref name="pmid18001374">{{cite journal | vauthors = Chinuck RS, Fortnum H, Baldwin DR | title = Appetite stimulants in cystic fibrosis: a systematic review | journal = Journal of Human Nutrition and Dietetics | volume = 20 | issue = 6 | pages = 526–537 | date = December 2007 | pmid = 18001374 | doi = 10.1111/j.1365-277X.2007.00824.x | s2cid = 22500622 }}</ref><ref name="pmid12647979">{{cite journal | vauthors = Davis MP, Khawam E, Pozuelo L, Lagman R | title = Management of symptoms associated with advanced cancer: olanzapine and mirtazapine. A World Health Organization project | journal = Expert Review of Anticancer Therapy | volume = 2 | issue = 4 | pages = 365–376 | date = August 2002 | pmid = 12647979 | doi = 10.1586/14737140.2.4.365 | s2cid = 72195061 }}</ref> * Insomnia<ref name="Clark_2011">{{cite journal | vauthors = Clark MS, Smith PO, Jamieson B | title = FPIN's clinical inquiries: Antidepressants for the treatment of insomnia in patients with depression | journal = American Family Physician | volume = 84 | issue = 9 | pages = 1–2 | date = November 2011 | pmid = 22164891 | url = http://www.aafp.org/afp/2011/1101/od1.pdf | access-date = 11 July 2017 | archive-date = 9 July 2020 | archive-url = https://web.archive.org/web/20200709135601/https://www.aafp.org/afp/2011/1101/od1.pdf | url-status = live }}</ref><ref>{{Cite journal|url=http://www.psychiatrictimes.com/sleep-disorders/effects-antidepressants-sleep|title=The Effects of Antidepressants on Sleep|journal=Psychiatric Times|date=13 June 2012|access-date=11 July 2017|vauthors=Winokur A, Demartinis N|volume=29|issue=6|archive-date=10 June 2020|archive-url=https://web.archive.org/web/20200610174804/https://www.psychiatrictimes.com/sleep-disorders/effects-antidepressants-sleep}}</ref> * Nausea and vomiting<ref name=Nut2002 /><ref name="pmid21602639">{{cite journal | vauthors = Li TC, Shiah IS, Sun CJ, Tzang RF, Huang KC, Lee WK | title = Mirtazapine relieves post-electroconvulsive therapy headaches and nausea: a case series and review of the literature | journal = The Journal of ECT | volume = 27 | issue = 2 | pages = 165–167 | date = June 2011 | pmid = 21602639 | doi = 10.1097/YCT.0b013e3181e63346 }}</ref><ref name="pmid17587360">{{cite journal | vauthors = Kast RE, Foley KF | title = Cancer chemotherapy and cachexia: mirtazapine and olanzapine are 5-HT3 antagonists with good antinausea effects | journal = European Journal of Cancer Care | volume = 16 | issue = 4 | pages = 351–354 | date = July 2007 | pmid = 17587360 | doi = 10.1111/j.1365-2354.2006.00760.x }}</ref> * Itching<ref name="pmid12509645">{{cite journal | vauthors = Twycross R, Greaves MW, Handwerker H, Jones EA, Libretto SE, Szepietowski JC, Zylicz Z | title = Itch: scratching more than the surface | journal = QJM | volume = 96 | issue = 1 | pages = 7–26 | date = January 2003 | pmid = 12509645 | doi = 10.1093/qjmed/hcg002 | doi-access = free }}</ref><ref name="pmid16297004">{{cite journal | vauthors = Greaves MW | title = Itch in systemic disease: therapeutic options | journal = Dermatologic Therapy | volume = 18 | issue = 4 | pages = 323–327 | year = 2005 | pmid = 16297004 | doi = 10.1111/j.1529-8019.2005.00036.x | s2cid = 3210356 | doi-access = free }}</ref> * Headaches and migraine<ref name="pmid21602639" /><ref name="pmid15549531">{{cite journal | vauthors = Colombo B, Annovazzi PO, Comi G | title = Therapy of primary headaches: the role of antidepressants | journal = Neurological Sciences | volume = 25 | issue = Suppl 3 | pages = S171–S175 | date = October 2004 | pmid = 15549531 | doi = 10.1007/s10072-004-0280-x | s2cid = 21285843 }}</ref><ref name="pmid17073214">{{cite journal | vauthors = Tajti J, Almási J | title = [Effects of mirtazapine in patients with chronic tension-type headache. Literature review] | language = hu | journal = Neuropsychopharmacologia Hungarica | volume = 8 | issue = 2 | pages = 67–72 | date = June 2006 | pmid = 17073214 }}</ref> {{div col end}}

==Adverse 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 tremors than tricyclic antidepressants, and less likely to cause nausea and sexual dysfunction than selective serotonin reuptake inhibitors.<ref name=Cochrane2011/>

Very common (≥10% incidence) adverse effects include constipation, dry mouth, sleepiness, increased appetite (17%) and weight gain (>7% increase in <50% of children).<ref name = "Remeron FDA label" /><ref name = AXIT>{{cite web|title=Axit Mirtazapine PRODUCT INFORMATION|url=https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2010-PI-05345-3|work=TGA eBusiness Services|publisher=alphapharm|access-date=15 October 2013|date=25 October 2011|archive-date=20 September 2020|archive-url=https://web.archive.org/web/20200920021431/https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2010-PI-05345-3|url-status=live}}</ref><ref name = EMC>{{cite web|title=Mirtazapine 30 mg Tablets – Summary of Product Characteristics|date=20 March 2013|access-date=24 October 2013|format=PDF|url=http://www.medicines.org.uk/emc/medicine/25201/SPC/Mirtazapine+30+mg+Tablets/|work=electronic Medicines Compendium|publisher=Sandoz Limited|archive-url=https://web.archive.org/web/20170731104144/http://www.medicines.org.uk/emc/medicine/25201/SPC/Mirtazapine+30+mg+Tablets/|archive-date=31 July 2017}}</ref><ref name = MS>{{cite web|title=mirtazapine (Rx) – Remeron, Remeron SolTab|work=Medscape|publisher=WebMD|access-date=24 October 2013|url=http://reference.medscape.com/drug/remeron-soltab-mirtazapine-342966|archive-date=29 October 2013|archive-url=https://web.archive.org/web/20131029200106/http://reference.medscape.com/drug/remeron-soltab-mirtazapine-342966|url-status=live}}</ref><ref name = "AMH">{{cite web | title = Australian Medicines Handbook | url = http://www.amh.net.au/ | year = 2013 | publisher = Australian Medicines Handbook Pty Ltd | access-date = 5 October 2013 | archive-date = 27 September 2011 | archive-url = https://web.archive.org/web/20110927131220/http://www.amh.net.au/ | url-status = live }}</ref><ref name = "BNF">{{cite book | title = British National Formulary (BNF) | year = 2013 | edition = 65th | publisher = Pharmaceutical Press | page = 1120 | isbn = 978-0-85711-084-8 | url = https://archive.org/details/bnf65britishnati0000unse | url-access = registration }}</ref><ref>{{cite web|title=Remeron (Mirtazapine) Drug Information|url=http://www.rxlist.com/remeron-drug/side-effects-interactions.htm|website=RxList|access-date=28 March 2016|archive-date=4 May 2017|archive-url=https://web.archive.org/web/20170504234252/http://www.rxlist.com/remeron-drug/side-effects-interactions.htm|url-status=live}}</ref><ref>{{cite journal | vauthors = Hummel J, Westphal S, Weber-Hamann B, Gilles M, Lederbogen F, Angermeier T, Luley C, Deuschle M, Kopf D | title = Serum lipoproteins improve after successful pharmacologic antidepressant treatment: a randomized open-label prospective trial | journal = The Journal of Clinical Psychiatry | volume = 72 | issue = 7 | pages = 885–891 | date = July 2011 | pmid = 21294998 | doi = 10.4088/JCP.09m05853blu }}</ref><ref>{{cite journal | vauthors = McIntyre RS, Soczynska JK, Konarski JZ, Kennedy SH | title = The effect of antidepressants on lipid homeostasis: a cardiac safety concern? | journal = Expert Opinion on Drug Safety | volume = 5 | issue = 4 | pages = 523–537 | date = July 2006 | pmid = 16774491 | doi = 10.1517/14740338.5.4.523 | s2cid = 23740352 }}</ref>

Common (1–10% incidence) adverse effects include weakness, confusion, dizziness, fasciculations (muscle twitches), peripheral edema (swelling, usually of the lower limbs), and abnormal lab results like elevated transaminases, elevated serum triglycerides, and elevated total cholesterol.<ref name = EMC/>

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 improve certain ones when taken in conjunction with them.<ref name=Ant2001/><ref name="pmid10333982"/> (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.<ref name=Ant2001/><ref name="pmid10333982"/>)

In general, some antidepressants, especially selective serotonin reuptake inhibitors, can paradoxically exacerbate some peoples' depression or anxiety or cause suicidal ideation.<ref name="pmid17143567">{{cite journal | vauthors = Möller HJ | title = Is there evidence for negative effects of antidepressants on suicidality in depressive patients? A systematic review | journal = European Archives of Psychiatry and Clinical Neuroscience | volume = 256 | issue = 8 | pages = 476–496 | date = December 2006 | pmid = 17143567 | doi = 10.1007/s00406-006-0689-8 | s2cid = 22708700 }}</ref> 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.<ref name="AHSF2018" />

Mirtazapine may induce arthralgia (non-inflammatory joint pain).<ref name=mirtaartha>{{cite journal | vauthors = Passier A, van Puijenbroek E | title = Mirtazapine-induced arthralgia | journal = British Journal of Clinical Pharmacology | volume = 60 | issue = 5 | pages = 570–572 | date = November 2005 | pmid = 16236049 | pmc = 1884949 | doi = 10.1111/j.1365-2125.2005.02481.x }}</ref>

A case report published in 2000 noted an instance in which mirtazapine counteracted the action of clonidine, causing a dangerous rise in blood pressure.<ref>{{cite journal | vauthors = Abo-Zena RA, Bobek MB, Dweik RA | title = Hypertensive urgency induced by an interaction of mirtazapine and clonidine | journal = Pharmacotherapy | volume = 20 | issue = 4 | pages = 476–478 | date = April 2000 | pmid = 10772378 | doi = 10.1592/phco.20.5.476.35061 | s2cid = 9959199 }}</ref>

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.<ref>{{cite journal | vauthors = Natter J, Yokoyama T, Michel B | title = Relative frequency of drug-induced sleep disorders for 32 antidepressants in a large set of Internet user reviews | journal = Sleep | volume = 44 | issue = 12 | article-number = zsab174 | date = December 2021 | pmid = 34252190 | doi = 10.1093/sleep/zsab174 | doi-access = free }}</ref>

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.<ref name="pmid35105363">{{cite journal | vauthors = Joseph RM, Jack RH, Morriss R, Knaggs RD, Butler D, Hollis C, Hippisley-Cox J, Coupland C | title = The risk of all-cause and cause-specific mortality in people prescribed mirtazapine: an active comparator cohort study using electronic health records | journal = BMC Med | volume = 20 | issue = 1 | article-number = 43 | date = February 2022 | pmid = 35105363 | pmc = 8809032 | doi = 10.1186/s12916-022-02247-x | url = | doi-access = free }}</ref>

=== Withdrawal === Stopping Mirtazapine and other antidepressants may cause withdrawal symptoms.<ref name="Ant2001" /><ref name="pmid11444761">{{cite journal | vauthors = Blier P | title = Pharmacology of rapid-onset antidepressant treatment strategies | journal = The Journal of Clinical Psychiatry | volume = 62 | issue = Suppl 15 | pages = 12–17 | year = 2001 | pmid = 11444761 }}</ref> A gradual and slow reduction in dose is recommended to minimize such symptoms.<ref name="pmid15819135">{{cite journal | vauthors = Vlaminck JJ, van Vliet IM, Zitman FG | title = [Withdrawal symptoms of antidepressants] | language = nl | journal = Nederlands Tijdschrift voor Geneeskunde | volume = 149 | issue = 13 | pages = 698–701 | date = March 2005 | pmid = 15819135 }}</ref> 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.<ref name="pmid10986577">{{cite journal | vauthors = Klesmer J, Sarcevic A, Fomari V | title = Panic attacks during discontinuation of mirtazepine | journal = Canadian Journal of Psychiatry | volume = 45 | issue = 6 | pages = 570–571 | date = August 2000 | pmid = 10986577 }}</ref><ref name="pmid10789310">{{cite journal | vauthors = MacCall C, Callender J | title = Mirtazapine withdrawal causing hypomania | journal = The British Journal of Psychiatry | volume = 175 | issue = 4 | page = 390 | date = October 1999 | pmid = 10789310 | doi = 10.1192/bjp.175.4.390a | doi-access = free }}</ref><ref name="pmid12776393">{{cite journal | vauthors = Ali S, Milev R | title = Switch to mania upon discontinuation of antidepressants in patients with mood disorders: a review of the literature | journal = Canadian Journal of Psychiatry | volume = 48 | issue = 4 | pages = 258–264 | date = May 2003 | pmid = 12776393 | doi = 10.1177/070674370304800410 | doi-access = free }}</ref>

==Overdose== Mirtazapine is considered to be relatively safe in the event of an overdose,<ref name="Maudsley"/> although it is considered slightly more toxic in overdose than most of the selective serotonin reuptake inhibitors (except citalopram).<ref>{{cite journal | vauthors = White N, Litovitz T, Clancy C | title = Suicidal antidepressant overdoses: a comparative analysis by antidepressant type | journal = Journal of Medical Toxicology | volume = 4 | issue = 4 | pages = 238–250 | date = December 2008 | pmid = 19031375 | pmc = 3550116 | doi = 10.1007/bf03161207 }}</ref> Unlike the tricyclic antidepressants, mirtazapine showed no significant cardiovascular adverse effects at 7 to 22 times the maximum recommended dose.<ref name="pmid10333982"/>

Twelve deaths have been attributed to mirtazapine overdose.<ref>{{cite journal | vauthors = Nikolaou P, Dona A, Papoutsis I, Spiliopoulou C, Maravelias C | title = Death Due to Mirtazapine Overdose | doi=10.1080/15563650902952273 | quote = Abstracts of the XXIX International Congress of the European Association of Poison Centres and Clinical Toxicologists, May 12–15, 2009, Stockholm, Sweden | year = 2009 | journal = Clinical Toxicology | volume = 47 | issue = 5 | pages = 436–510 |s2cid=218861198 | doi-access = free }}</ref><ref>{{cite book | vauthors = Baselt RC | title = Disposition of Toxic Drugs and Chemicals in Man | edition = 8th | publisher = Biomedical Publications | location = Foster City, CA | year = 2008 | pages = 1045–7 | isbn = 978-0-9626523-7-0 }}</ref> The fatal toxicity index (deaths per million prescriptions) for mirtazapine is 3.1 (95% CI: 0.1 to 17.2).<ref name=":0" /> This is similar to that observed with selective serotonin reuptake inhibitors.<ref name="bmj325">{{cite journal | vauthors = Buckley NA, McManus PR | title = Fatal toxicity of serotonergic and other antidepressant drugs: analysis of United Kingdom mortality data | journal = BMJ | volume = 325 | issue = 7376 | pages = 1332–1333 | date = December 2002 | pmid = 12468481 | pmc = 137809 | doi = 10.1136/bmj.325.7376.1332 }}</ref>{{Unreliable medical source|date=October 2011}}

==Interactions== Concurrent use with inhibitors or inducers of the cytochrome P450 isoenzymes CYP1A2, CYP2D6, or CYP3A4 can result in altered concentrations of mirtazapine, as these are the main enzymes responsible for its metabolism.<ref name="pmid10885584"/><ref name=Ant2001 /> As examples, fluoxetine and paroxetine, inhibitors of these enzymes, are known to modestly increase mirtazapine levels, while carbamazepine, an inducer, considerably decreases them.<ref name="pmid10885584" /> 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%.<ref name="pmid10885584" />

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. Several case reports document serotonin syndrome induced by the combination of mirtazapine with other agents (olanzapine,<ref>{{cite journal | vauthors = Wu CS, Tong SH, Ong CT, Sung SF | title = Serotonin Syndrome Induced by Combined Use of Mirtazapine and Olanzapine Complicated with Rhabdomyolysis, Acute Renal Failure, and Acute Pulmonary Edema-A Case Report | journal = Acta Neurologica Taiwanica | volume = 24 | issue = 4 | pages = 117–121 | date = December 2015 | pmid = 27333965 }}</ref> quetiapine,<ref>{{cite journal | vauthors = Saguin E, Keou S, Ratnam C, Mennessier C, Delacour H, Lahutte B | title = Severe rhabdomyolysis induced by quetiapine and mirtazapine in a French military soldier | journal = Journal of the Royal Army Medical Corps | volume = 164 | issue = 2 | pages = 127–129 | date = May 2018 | pmid = 29632134 | doi = 10.1136/jramc-2018-000939 | s2cid = 4737517 }}</ref> tramadol and venlafaxine<ref>{{cite journal | vauthors = Houlihan DJ | title = Serotonin syndrome resulting from coadministration of tramadol, venlafaxine, and mirtazapine | journal = The Annals of Pharmacotherapy | volume = 38 | issue = 3 | pages = 411–413 | date = March 2004 | pmid = 14970364 | doi = 10.1345/aph.1D344 | s2cid = 33912489 }}</ref>). Adding fluvoxamine to treatment with mirtazapine may cause a significant increase in mirtazapine concentration. This interaction may necessitate an adjustment of the mirtazapine dosage.<ref>{{cite journal | vauthors = Anttila AK, Rasanen L, Leinonen EV | title = Fluvoxamine augmentation increases serum mirtazapine concentrations three- to fourfold | journal = The Annals of Pharmacotherapy | volume = 35 | issue = 10 | pages = 1221–1223 | date = October 2001 | pmid = 11675851 | doi = 10.1345/aph.1A014 | s2cid = 44807359 }}</ref><ref>{{Cite web |title=Fluvoxamine and mirtazapine Interactions |url=https://www.drugs.com/drug-interactions/fluvoxamine-with-mirtazapine-1128-0-1640-0.html |access-date=4 December 2022 |website=Drugs.com |archive-date=4 December 2022 |archive-url=https://web.archive.org/web/20221204190716/https://www.drugs.com/drug-interactions/fluvoxamine-with-mirtazapine-1128-0-1640-0.html |url-status=live }}</ref>

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.<ref name="AHSF2018" />

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.<ref name="pmid16460699" /> This is per the fact that the 5-HT_2A receptor is the predominant serotonin receptor thought to be involved in the pathophysiology of serotonin syndrome (with the 5-HT_1A receptor seeming to be protective).<ref name="pmid16460699" /><ref name="pmid16342227" /> Mirtazapine is a potent 5-HT_2A receptor antagonist, and cyproheptadine, a medication that shares this property, mediates recovery from serotonin syndrome and is an antidote against it.<ref name="pmid16342227" /><ref name="pmid23145389">{{cite journal | vauthors = Iqbal MM, Basil MJ, Kaplan J, Iqbal MT | title = Overview of serotonin syndrome | journal = Annals of Clinical Psychiatry | volume = 24 | issue = 4 | pages = 310–318 | date = November 2012 | pmid = 23145389 }}</ref>

There is a possible interaction that results in a hypertensive crisis when mirtazapine is given to a patient who 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.<ref>{{cite web|url=https://www.reliasmedia.com/articles/46173-interaction-between-mirtazapine-and-clonidine|title=Interactions Between Mirtazapine and Clonidine|access-date=15 January 2021|archive-date=21 January 2021|archive-url=https://web.archive.org/web/20210121041118/https://www.reliasmedia.com/articles/46173-interaction-between-mirtazapine-and-clonidine|url-status=live}}</ref>

Mirtazapine has been used as a hallucinogen antidote to block the effects of serotonergic psychedelics like psilocybin and lysergic acid diethylamide (LSD).<ref name="YatesMelon2024">{{cite journal | vauthors = Yates G, Melon E | title = Trip-killers: a concerning practice associated with psychedelic drug use | journal = Emerg Med J | volume = 41 | issue = 2 | pages = 112–113 | date = January 2024 | pmid = 38123961 | doi = 10.1136/emermed-2023-213377 | url = https://s3.amazonaws.com/crawl.prod.proquest.com/fpcache/71f445805bfb61341cbc438c8ae23bd3.pdf?X-Amz-Security-Token=IQoJb3JpZ2luX2VjEBMaCXVzLWVhc3QtMSJIMEYCIQDETX7YpaG5THA%2FNbKR0d92wr6h%2Bgg9preNcKjAsEqo%2BQIhAIlPGGWOeUc23LqhBzRYbxvSXB9aqSe2vVonl4nacAhhKp0CCLz%2F%2F%2F%2F%2F%2F%2F%2F%2F%2FwEQABoMNTE4MzQ2ODQ4MzQxIgy9ji58Qtbi%2BavuKeYq8QEDL1U5KZDQ0bXFyVapeqJgE%2FX6x8DcJfFU8DAXYZPSQEwrIdfPbZWcYsH340deru%2FUHnNaGGpuHFoVzui%2FMbqBz7MANcowj%2FL1%2BQZzQ5hXh5KM3BW8E6NRzrQyuPRmBy7kQUkx8%2BjTN%2BXSMgF%2FCAs6Dn9fScgBGz3ddkwRZXDkjasqMP65RCPKhagK68cyMbf3oX%2BKS8a4Kltc2rk3CnWEhOKrZU4mIxq07DikLAXQbl8YRZJIkeOhN5TgBaLWJqyn1td2VWCMymAaFsqtPWHwXnEfsolRlfDooe6QXfE2YwX5PxBVJU7GPXRgrAqPjwtJMOCHgsEGOpwBYif%2BaDMBdz3IEghuvCvorAS0mkHzdcOz%2Fi7AzuN9nch%2FIm8llhMsN41aAWHuSG25pnhhftauFsg7rbGsrW2nl2kq2upi9zP7y%2Fnqk93jcP0kr0jM8zU12bYoSTsToQJsshH4N%2BTQUMwlzRQfeVv8MXdq%2BgSTTzJrWNwT1yNzye3rSHjvOumbNl6sgBISw7QqRzhB6hZTuf8AcI%2B7&X-Amz-Algorithm=AWS4-HMAC-SHA256&X-Amz-Date=20250511T111826Z&X-Amz-SignedHeaders=host&X-Amz-Credential=ASIAXRL7BHBKRAKCQVVB%2F20250511%2Fus-east-1%2Fs3%2Faws4_request&X-Amz-Expires=3600&X-Amz-Signature=20bb1b90e4c8dbaa4115c954387617ebe2f55269bdd517692f1380193ed3f769 | archive-url = https://web.archive.org/web/20250511111827/https://s3.amazonaws.com/crawl.prod.proquest.com/fpcache/71f445805bfb61341cbc438c8ae23bd3.pdf?X-Amz-Security-Token=IQoJb3JpZ2luX2VjEBMaCXVzLWVhc3QtMSJIMEYCIQDETX7YpaG5THA%2FNbKR0d92wr6h%2Bgg9preNcKjAsEqo%2BQIhAIlPGGWOeUc23LqhBzRYbxvSXB9aqSe2vVonl4nacAhhKp0CCLz%2F%2F%2F%2F%2F%2F%2F%2F%2F%2FwEQABoMNTE4MzQ2ODQ4MzQxIgy9ji58Qtbi%2BavuKeYq8QEDL1U5KZDQ0bXFyVapeqJgE%2FX6x8DcJfFU8DAXYZPSQEwrIdfPbZWcYsH340deru%2FUHnNaGGpuHFoVzui%2FMbqBz7MANcowj%2FL1%2BQZzQ5hXh5KM3BW8E6NRzrQyuPRmBy7kQUkx8%2BjTN%2BXSMgF%2FCAs6Dn9fScgBGz3ddkwRZXDkjasqMP65RCPKhagK68cyMbf3oX%2BKS8a4Kltc2rk3CnWEhOKrZU4mIxq07DikLAXQbl8YRZJIkeOhN5TgBaLWJqyn1td2VWCMymAaFsqtPWHwXnEfsolRlfDooe6QXfE2YwX5PxBVJU7GPXRgrAqPjwtJMOCHgsEGOpwBYif%2BaDMBdz3IEghuvCvorAS0mkHzdcOz%2Fi7AzuN9nch%2FIm8llhMsN41aAWHuSG25pnhhftauFsg7rbGsrW2nl2kq2upi9zP7y%2Fnqk93jcP0kr0jM8zU12bYoSTsToQJsshH4N%2BTQUMwlzRQfeVv8MXdq%2BgSTTzJrWNwT1yNzye3rSHjvOumbNl6sgBISw7QqRzhB6hZTuf8AcI%2B7&X-Amz-Algorithm=AWS4-HMAC-SHA256&X-Amz-Date=20250511T111826Z&X-Amz-SignedHeaders=host&X-Amz-Credential=ASIAXRL7BHBKRAKCQVVB%2F20250511%2Fus-east-1%2Fs3%2Faws4_request&X-Amz-Expires=3600&X-Amz-Signature=20bb1b90e4c8dbaa4115c954387617ebe2f55269bdd517692f1380193ed3f769 | archive-date = 2025-05-11 }}</ref><ref name="Suran2024">{{cite journal | vauthors = Suran M | title = Study Finds Hundreds of Reddit Posts on "Trip-Killers" for Psychedelic Drugs | journal = JAMA | volume = 331 | issue = 8 | pages = 632–634 | date = February 2024 | pmid = 38294772 | doi = 10.1001/jama.2023.28257 | url = }}</ref>

==Pharmacology==

===Pharmacodynamics=== {{See also|Pharmacology of antidepressants|Tetracyclic antidepressant#Pharmacology}} {| class="wikitable floatright sortable" style="font-size:small;" |+Mirtazapine<ref name="PDSP">{{cite web|url=https://pdsp.unc.edu/databases/pdsp.php?receptorDD=&receptor=&speciesDD=&species=&sourcesDD=&source=&hotLigandDD=&hotLigand=&testLigandDD=&testFreeRadio=testFreeRadio&testLigand=mirtazepine&referenceDD=&reference=&KiGreater=&KiLess=&kiAllRadio=all&doQuery=Submit+Query|title=PDSP K_i Database|author1-link=Bryan Roth|vauthors=Roth BL, Driscol J|work=Psychoactive Drug Screening Program (PDSP)|publisher=University of North Carolina at Chapel Hill and the United States National Institute of Mental Health|access-date=14 August 2017|archive-date=28 August 2021|archive-url=https://web.archive.org/web/20210828173607/https://pdsp.unc.edu/databases/pdsp.php?receptorDD=&receptor=&speciesDD=&species=&sourcesDD=&source=&hotLigandDD=&hotLigand=&testLigandDD=&testFreeRadio=testFreeRadio&testLigand=mirtazepine&referenceDD=&reference=&KiGreater=&KiLess=&kiAllRadio=all&doQuery=Submit+Query|url-status=live}}</ref> |- ! data-sort-type=number | !!''K''_i (nM) !! Species !! Ref |- | {{abbrlink|SERT|Serotonin transporter}} || 10000+ || Human || <ref name="pmid9537821">{{cite journal | vauthors = Tatsumi M, Groshan K, Blakely RD, Richelson E | title = Pharmacological profile of antidepressants and related compounds at human monoamine transporters | journal = European Journal of Pharmacology | volume = 340 | issue = 2–3 | pages = 249–258 | date = December 1997 | pmid = 9537821 | doi = 10.1016/s0014-2999(97)01393-9 }}</ref><ref name="pmid16517171" /> |- | {{abbrlink|NET|Norepinephrine transporter}} || 4600+ || Human || <ref name="pmid17471183" /><ref name="pmid9537821" /> |- | {{abbrlink|DAT|Dopamine transporter}} || 10000+ || Human || <ref name="pmid9537821" /><ref name="pmid16517171" /> |- | 5-HT_1A || data-sort-value=3330 | 3330–5010 || Human || <ref name=Ant2001 /><ref name="pmid16517171" /> |- | 5-HT_1B || data-sort-value=3534 | 3534–12600 || Human || <ref name=Ant2001 /><ref name="pmid16517171" /> |- | 5-HT_1D || 794–5010 || Human || <ref name=Ant2001 /><ref name="pmid16517171" /> |- | 5-HT_1E || 728 || Human || <ref name="pmid16517171" /> |- | 5-HT_1F || 583 || Human || <ref name="pmid16517171" /> |- | '''5-HT_2A''' || data-sort-value=6 |'''6.3–69'''|| '''Human'''|| <ref name=Ant2001 /><ref name="pmid16517171" /> |- | 5-HT_2B ||200|| Human || <ref name=Ant2001 /> |- | '''5-HT_2C''' || data-sort-value=8 |'''8.9–39'''|| '''Human'''|| <ref name=Ant2001 /><ref name="pmid16517171" /> |- | '''5-HT₃'''|| '''8.1'''<br />70 ({{abbr|IC₅₀|Half-maximal inhibitory concentration}}) || '''Human'''||<ref name="A review of the pharmacological and">{{cite journal | vauthors = Anttila SA, Leinonen EV | title = A review of the pharmacological and clinical profile of mirtazapine | journal = CNS Drug Reviews | volume = 7 | issue = 3 | pages = 249–264 | date = 2001 | pmid = 11607047 | pmc = 6494141 | doi = 10.1111/j.1527-3458.2001.tb00198.x }}</ref><br /><ref name=" Eisensamer" /> |- | 5-HT_4L || 10000+ || Human || <ref name="pmid16517171" /> |- | 5-HT_5A || 670 || Human || <ref name="pmid16517171" /> |- | 5-HT₆ || {{abbr|ND|No data}} || {{abbr|ND|No data}} || {{abbr|ND|No data}}<ref name="pmid16517171" /> |- | 5-HT₇ ||265|| Human || <ref name="pmid16517171" /> |- | α_1A ||1815|| Human || <ref name="pmid16517171" /> |- | '''α_2A''' ||'''20–158'''|| '''Human'''|| <ref name="pmid16517171" /><ref name="Proudman" /> |- | α_2B ||88|| Human || <ref name="pmid16517171" /> |- | '''α_2C''' ||'''18–110'''|| '''Human'''|| <ref name="pmid16517171" /><ref name="Proudman" /> |- | β || 10000+ || Human || <ref name="pmid16517171" /> |- | D₁ || data-sort-value=4167 | 4167 || Rat || |- | D₂ || 5454+ || Human || <ref name="pmid16517171" /> |- | D₃ || data-sort-value=5723 | 5723 || Human ||<ref name="pmid16517171" /> |- | D₄ || data-sort-value=2518 | 2518 || Human || <ref name="pmid16517171" /> |- | '''H₁''' ||'''0.14–1.6'''|| '''Human'''|| <ref name="pmid22033803">{{cite journal | vauthors = Appl H, Holzammer T, Dove S, Haen E, Strasser A, Seifert R | title = Interactions of recombinant human histamine H₁R, H₂R, H₃R, and H₄R receptors with 34 antidepressants and antipsychotics | journal = Naunyn-Schmiedeberg's Archives of Pharmacology | volume = 385 | issue = 2 | pages = 145–170 | date = February 2012 | pmid = 22033803 | doi = 10.1007/s00210-011-0704-0 | s2cid = 14274150 }}</ref><ref name=Ant2001/><ref name="pmid16517171">{{cite journal | vauthors = Van der Mey M, Windhorst AD, Klok RP, Herscheid JD, Kennis LE, Bischoff F, Bakker M, Langlois X, Heylen L, Jurzak M, Leysen JE | title = Synthesis and biodistribution of [11C]R107474, a new radiolabeled alpha2-adrenoceptor antagonist | journal = Bioorganic & Medicinal Chemistry | volume = 14 | issue = 13 | pages = 4526–4534 | date = July 2006 | pmid = 16517171 | doi = 10.1016/j.bmc.2006.02.029 }}</ref> |- | H₂ || 10000+ || Rat || <ref name="pmid3419539">{{cite journal | vauthors = de Boer TH, Maura G, Raiteri M, de Vos CJ, Wieringa J, Pinder RM | title = Neurochemical and autonomic pharmacological profiles of the 6-aza-analogue of mianserin, Org 3770 and its enantiomers | journal = Neuropharmacology | volume = 27 | issue = 4 | pages = 399–408 | date = April 1988 | pmid = 3419539 | doi = 10.1016/0028-3908(88)90149-9 | s2cid = 582691 }}</ref><ref name="pmid22033803" /> |- | H₃ || data-sort-value=83200 | 83200 || Human || <ref name="pmid22033803" /> |- | H₄ || 100000+ || Human || <ref name="pmid22033803" /> |- | {{abbrlink|mACh|Muscarinic acetylcholine receptor}} || 670 || Human || <ref name=Ant2001 /><ref name="pmid17471183">{{cite journal | vauthors = Gillman PK | title = Tricyclic antidepressant pharmacology and therapeutic drug interactions updated | journal = British Journal of Pharmacology | volume = 151 | issue = 6 | pages = 737–748 | date = July 2007 | pmid = 17471183 | pmc = 2014120 | doi = 10.1038/sj.bjp.0707253 }}</ref> |- | {{abbrlink|VGSC|Voltage-gated sodium channel}} || data-sort-value=6905 | 6905 || Rat || <ref name="pmid16517171" /> |- | {{abbrlink|VDCC|Voltage-dependent calcium channel}} || 10000+ || Rat || <ref name="pmid16517171" /> |- class="sortbottom" | colspan="4" style="width: 1px;" | 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),<ref name=Ant2001 /> although the actual evidence in support of this label has been regarded as poor.<ref name="pmid16342227" /> It is a tetracyclic piperazine-azepine.<ref>{{cite web|title=Mirtazapine|url=https://www.drugbank.ca/drugs/DB00370|website=Drugbank|access-date=16 January 2020|archive-date=19 August 2020|archive-url=https://web.archive.org/web/20200819113616/https://www.drugbank.ca/drugs/DB00370|url-status=live}}</ref>

Mirtazapine has antihistamine, α₂-blocker, and antiserotonergic activity.<ref name=Ant2001 /><ref name="pmid9090573">{{cite journal | vauthors = Frazer A | title = Pharmacology of antidepressants | journal = Journal of Clinical Psychopharmacology | volume = 17 | issue = Suppl 1 | pages = 2S–18S | date = April 1997 | pmid = 9090573 | doi = 10.1097/00004714-199704001-00002 }}</ref> It is specifically a potent antagonist or inverse agonist of the α_2A-, α_2B-, and α_2C-adrenergic receptors,<ref name="Proudman">{{cite journal |vauthors = Proudman R, Akinaga J, Baker JG|title=The affinity and selectivity of α-adrenoceptor antagonists, antidepressants and antipsychotics for the human α2A, α2B, and α2C-adrenoceptors and comparison with human α1 and β-adrenoceptors |journal=Pharmacology Research & Perspectives |date=February 2022 |volume=10 |issue=2 |pages=18 |doi=10.1002/prp2.936 |pmid=35224877 |pmc=8882856 |url=https://bpspubs.onlinelibrary.wiley.com/doi/10.1002/prp2.936}}</ref> the serotonin 5-HT_2A, 5-HT_2C, and the histamine H₁ receptor.<ref name=Ant2001 /><ref name="pmid9090573" /> Unlike many other antidepressants, it does not inhibit the reuptake of serotonin, norepinephrine, or dopamine,<ref name=Ant2001 /><ref name="pmid9090573" /> nor does it inhibit monoamine oxidase.<ref name="pmid21200377">{{cite journal | vauthors = Fisar Z, Hroudová J, Raboch J | title = Inhibition of monoamine oxidase activity by antidepressants and mood stabilizers | journal = Neuro Endocrinology Letters | volume = 31 | issue = 5 | pages = 645–656 | year = 2010 | pmid = 21200377 }}</ref> Similarly, mirtazapine has weak or no activity as an anticholinergic or blocker of sodium or calcium channels, in contrast to most tricyclic antidepressants.<ref name=Ant2001 /><ref name="pmid16517171" /><ref name="pmid9090573" /> In accordance, it has better tolerability and low toxicity in overdose.<ref name=Ant2001 /><ref name="pmid11357798">{{cite journal | vauthors = Richelson E | title = Pharmacology of antidepressants | journal = Mayo Clinic Proceedings | volume = 76 | issue = 5 | pages = 511–527 | date = May 2001 | pmid = 11357798 | doi = 10.4065/76.5.511 | doi-access = free }}</ref> As an H₁ receptor antagonist, mirtazapine is extremely potent, and is in fact one of the most potent H₁ receptor inverse agonists among tricyclic and tetracyclic antidepressants and most antihistamines in general.<ref name="pmid17471183" /><ref name="BruntonChabner2011">{{cite book| vauthors = Brunton L, Chabner BA, Knollman B |title=Goodman and Gilman's The Pharmacological Basis of Therapeutics | edition = Twelfth | url= https://books.google.com/books?id=e_yAOpyyaowC|date=14 January 2011|publisher=McGraw Hill Professional|isbn=978-0-07-176939-6|page=410}}</ref><ref name="SchatzbergNemeroff2017">{{cite book|vauthors=Schatzberg AF, Nemeroff CB|title=The American Psychiatric Association Publishing Textbook of Psychopharmacology|url=https://books.google.com/books?id=v9wnDwAAQBAJ&pg=PA322|date=10 May 2017|publisher=American Psychiatric Pub|isbn=978-1-61537-122-8|pages=322–|access-date=14 August 2017|archive-date=10 January 2023|archive-url=https://web.archive.org/web/20230110194022/https://books.google.com/books?id=v9wnDwAAQBAJ&pg=PA322|url-status=live}}</ref> 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.<ref name=Ant2001 /><ref name="pmid16517171" />

The (''S'')-(+) enantiomer of mirtazapine is responsible for antagonism of the serotonin 5-HT_2A and 5-HT_2C receptors,<ref name = MD/> while the (''R'')-(–) enantiomer is responsible for antagonism of the 5-HT₃ receptor.<ref name = MD>{{cite book|veditors=Brayfield A|chapter=Mirtazapine|title=Martindale: The Complete Drug Reference|publisher=The Royal Pharmaceutical Society of Great Britain|access-date=3 November 2013|date=30 January 2013|chapter-url=http://www.medicinescomplete.com/mc/martindale/current/11022-r.htm|archive-date=14 January 2021|archive-url=https://web.archive.org/web/20210114165327/https://about.medicinescomplete.com/|url-status=live}}</ref> Both enantiomers are involved in antagonism of the H₁ and α₂-adrenergic receptors,<ref name = AXIT/><ref name = MD/> although the (''S'')-(+) enantiomer is the stronger antihistamine.<ref name="pmid23728612" />

Although not clinically relevant, mirtazapine has been found to act as a partial agonist of the κ-opioid receptor at high concentrations (EC₅₀ = 7200nM).<ref name="pmid22708686">{{cite journal | vauthors = Olianas MC, Dedoni S, Onali P | title = The atypical antidepressant mianserin exhibits agonist activity at κ-opioid receptors | journal = British Journal of Pharmacology | volume = 167 | issue = 6 | pages = 1329–1341 | date = November 2012 | pmid = 22708686 | pmc = 3504997 | doi = 10.1111/j.1476-5381.2012.02078.x }}</ref>

====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-HT_1A 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.<ref name=Ant2001/><ref name="pmid10446735"/><ref name="pmid7912194">{{cite journal | vauthors = De Boer T, Nefkens F, Van Helvoirt A | title = The alpha 2-adrenoceptor antagonist Org 3770 enhances serotonin transmission in vivo | journal = European Journal of Pharmacology | volume = 253 | issue = 1–2 | pages = R5–R6 | date = February 1994 | pmid = 7912194 | doi = 10.1016/0014-2999(94)90778-1 }}</ref>{{Unreliable medical source|date=October 2011}}<ref name="pmid9361334">{{cite journal | vauthors = Berendsen HH, Broekkamp CL | title = Indirect in vivo 5-HT1A-agonistic effects of the new antidepressant mirtazapine | journal = Psychopharmacology | volume = 133 | issue = 3 | pages = 275–282 | date = October 1997 | pmid = 9361334 | doi = 10.1007/s002130050402 | s2cid = 230492 }}</ref><ref name="pmid15145142">{{cite journal | vauthors = Nakayama K, Sakurai T, Katsu H | title = Mirtazapine increases dopamine release in prefrontal cortex by 5-HT1A receptor activation | journal = Brain Research Bulletin | volume = 63 | issue = 3 | pages = 237–241 | date = April 2004 | pmid = 15145142 | doi = 10.1016/j.brainresbull.2004.02.007 | s2cid = 14393829 }}</ref>{{Unreliable medical source|date=October 2011}} Because of this, mirtazapine has been said to be a functional "indirect agonist" of the 5-HT_1A receptor.<ref name="pmid9361334"/> Increased activation of the central 5-HT_1A receptor is thought to be a major mediator of efficacy of most antidepressant drugs.<ref name="pmid11212592">{{cite journal | vauthors = Blier P, Abbott FV | title = Putative mechanisms of action of antidepressant drugs in affective and anxiety disorders and pain | journal = Journal of Psychiatry & Neuroscience | volume = 26 | issue = 1 | pages = 37–43 | date = January 2001 | pmid = 11212592 | pmc = 1408043 | url = http://www.cma.ca/multimedia/staticContent/HTML/N0/l2/jpn/vol-26/issue-1/pdf/pg37.pdf | access-date = 20 June 2009 | archive-url = https://web.archive.org/web/20160306214237/https://www.cma.ca/multimedia/staticContent/HTML/N0/l2/jpn/vol-26/issue-1/pdf/pg37.pdf | archive-date = 6 March 2016 }}</ref>

====5-HT₂ receptor==== Antagonism of the 5-HT₂ 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.<ref name="pmid16433010">{{cite journal | vauthors = Millan MJ | title = Serotonin 5-HT2C receptors as a target for the treatment of depressive and anxious states: focus on novel therapeutic strategies | journal = Therapie | volume = 60 | issue = 5 | pages = 441–460 | year = 2005 | pmid = 16433010 | doi = 10.2515/therapie:2005065 }}</ref><ref name="pmid18709360">{{cite journal | vauthors = Dekeyne A, Millan MJ | title = Discriminative stimulus properties of the atypical antidepressant, mirtazapine, in rats: a pharmacological characterization | journal = Psychopharmacology | volume = 203 | issue = 2 | pages = 329–341 | date = April 2009 | pmid = 18709360 | doi = 10.1007/s00213-008-1259-8 | doi-access = free }}</ref> Mirtazapine increases dopamine release in the prefrontal cortex.<ref>[https://web.archive.org/web/20180109064133/https://pdfs.semanticscholar.org/4ab3/7aa1be6b898432f5faf5d5ff4a780e106a7b.pdf Mirtazapine increases dopamine release in prefrontal cortex by 5-HT1A receptor activation.]</ref><ref name="pmid10762339"/> Accordingly, it was shown that by blocking the α₂-adrenergic receptors and 5-HT_2C receptors mirtazapine disinhibited dopamine and norepinephrine activity in these areas in rats.<ref name="pmid10762339">{{cite journal | vauthors = Millan MJ, Gobert A, Rivet JM, Adhumeau-Auclair A, Cussac D, Newman-Tancredi A, Dekeyne A, Nicolas JP, Lejeune F | title = Mirtazapine enhances frontocortical dopaminergic and corticolimbic adrenergic, but not serotonergic, transmission by blockade of alpha2-adrenergic and serotonin2C receptors: a comparison with citalopram | journal = The European Journal of Neuroscience | volume = 12 | issue = 3 | pages = 1079–1095 | date = March 2000 | pmid = 10762339 | doi = 10.1046/j.1460-9568.2000.00982.x | s2cid = 23098292 | doi-access = free }}</ref> In addition, mirtazapine's antagonism of 5-HT_2A receptors has beneficial effects on anxiety, sleep and appetite, as well as sexual function regarding the latter receptor.<ref name=Ant2001/><ref name="pmid10333982">{{cite journal | vauthors = Fawcett J, Barkin RL | title = Review of the results from clinical studies on the efficacy, safety and tolerability of mirtazapine for the treatment of patients with major depression | journal = Journal of Affective Disorders | volume = 51 | issue = 3 | pages = 267–285 | date = December 1998 | pmid = 10333982 | doi = 10.1016/S0165-0327(98)00224-9 }}</ref> Mirtazapine has been shown to lower drug seeking behaviour (more specifically to methamphetamine) in various human and animal studies.<ref name="Graves_2012">{{cite journal | vauthors = Graves SM, Napier TC | title = SB 206553, a putative 5-HT2C inverse agonist, attenuates methamphetamine-seeking in rats | journal = BMC Neuroscience | volume = 13 | issue = 1 | article-number = 65 | date = June 2012 | pmid = 22697313 | pmc = 3441362 | doi = 10.1186/1471-2202-13-65 | doi-access = free }}</ref><ref name="pmid22065532">{{cite journal | vauthors = Colfax GN, Santos GM, Das M, Santos DM, Matheson T, Gasper J, Shoptaw S, Vittinghoff E | title = Mirtazapine to reduce methamphetamine use: a randomized controlled trial | journal = Archives of General Psychiatry | volume = 68 | issue = 11 | pages = 1168–1175 | date = November 2011 | pmid = 22065532 | pmc = 3437988 | doi = 10.1001/archgenpsychiatry.2011.124 }}</ref><ref name="pmid18945553">{{cite journal | vauthors = Herrold AA, Shen F, Graham MP, Harper LK, Specio SE, Tedford CE, Napier TC | title = Mirtazapine treatment after conditioning with methamphetamine alters subsequent expression of place preference | journal = Drug and Alcohol Dependence | volume = 99 | issue = 1–3 | pages = 231–239 | date = January 2009 | pmid = 18945553 | doi = 10.1016/j.drugalcdep.2008.08.005 }}</ref> It is also being investigated in substance abuse disorders to reduce withdrawal effects and improve remission rates.<ref name="Graves_2012"/><ref name="pmid18633741">{{cite journal | vauthors = Rose ME, Grant JE | title = Pharmacotherapy for methamphetamine dependence: a review of the pathophysiology of methamphetamine addiction and the theoretical basis and efficacy of pharmacotherapeutic interventions | journal = Annals of Clinical Psychiatry | volume = 20 | issue = 3 | pages = 145–155 | year = 2008 | pmid = 18633741 | doi = 10.1080/10401230802177656 }}</ref><ref name="pmid22095579">{{cite journal | vauthors = Brackins T, Brahm NC, Kissack JC | title = Treatments for methamphetamine abuse: a literature review for the clinician | journal = Journal of Pharmacy Practice | volume = 24 | issue = 6 | pages = 541–550 | date = December 2011 | pmid = 22095579 | doi = 10.1177/0897190011426557 | s2cid = 37335642 }}</ref><ref name="pmid23617468">{{cite journal | vauthors = Brensilver M, Heinzerling KG, Shoptaw S | title = Pharmacotherapy of amphetamine-type stimulant dependence: an update | journal = Drug and Alcohol Review | volume = 32 | issue = 5 | pages = 449–460 | date = September 2013 | pmid = 23617468 | pmc = 4251965 | doi = 10.1111/dar.12048 }}</ref>

Mirtazapine significantly improves pre-existing symptoms of nausea, vomiting, diarrhea, and irritable bowel syndrome in affected individuals.<ref name="pmid11585276">{{cite journal | vauthors = Kast RE | title = Mirtazapine may be useful in treating nausea and insomnia of cancer chemotherapy | journal = Supportive Care in Cancer | volume = 9 | issue = 6 | pages = 469–470 | date = September 2001 | pmid = 11585276 | doi = 10.1007/s005200000215 | s2cid = 24132032 }}</ref> Mirtazapine may be used as an inexpensive antiemetic alternative to Ondansetron.<ref name="pmid17587360"/> In conjunction with substance abuse counseling, mirtazapine has been investigated for the purpose of reducing methamphetamine use in dependent individuals with success.<ref name="pmid22065532" /><ref name="pmid18633741" /><ref name="pmid22095579" /><ref name="pmid23617468" /> In contrast to mirtazapine, the selective serotonin reuptake inhibitors, serotonin–norepinephrine reuptake inhibitors, monoamine oxidase inhibitors, and some tricyclic antidepressants acutely increase the general activity of the 5-HT_2A, 5-HT_2C, and 5-HT₃ receptors, leading to a number of negative changes and side effects, the most prominent of which include anorexia, insomnia, nausea, and diarrhea, among others. However, most of these adverse effects are temporary, since down regulation of 5-HT_2A receptors eventually occurs following chronic SSRI treatment, and desensitization of 5-HT₃ receptors often occurs within a week or less. This is precisely why SSRIs have a delayed antidepressant and anxiolytic effect, and occasionally, an acute anxiogenic effect before down regulation occurs. Mirtazapine, on the other hand, is an antagonist of the 5-HT_2A receptor, and antagonists at this receptor typically induce reverse tolerance.<ref>{{cite journal | vauthors = Yadav PN, Kroeze WK, Farrell MS, Roth BL | title = Antagonist functional selectivity: 5-HT2A serotonin receptor antagonists differentially regulate 5-HT2A receptor protein level in vivo | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 339 | issue = 1 | pages = 99–105 | date = October 2011 | pmid = 21737536 | pmc = 3186284 | doi = 10.1124/jpet.111.183780 }}</ref> Thus, the antidepressant and anxiolytic effects of mirtazapine occur more rapidly than with SSRIs. Furthermore, its reduced incidence of sexual dysfunction (such as loss of libido and anorgasmia) could be a product of negligible binding to the serotonin transporter and antagonism of the 5-HT_2A receptors; however, Mirtazapine's high affinity towards and inverse agonism of the 5-HT_2C 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-HT_2C 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.<ref name="pmid10333982"/><ref name="pmid15560319">{{cite journal | vauthors = Caldis EV, Gair RD | title = Mirtazapine for treatment of nausea induced by selective serotonin reuptake inhibitors | journal = Canadian Journal of Psychiatry | volume = 49 | issue = 10 | page = 707 | date = October 2004 | pmid = 15560319 | doi = 10.1177/070674370404901014 | doi-access = free }}</ref>

Mirtazapine does not have pro-serotonergic activity and thus does not cause serotonin syndrome.<ref name="pmid16342227">{{cite journal | vauthors = Gillman PK | title = A systematic review of the serotonergic effects of mirtazapine in humans: implications for its dual action status | journal = Human Psychopharmacology | volume = 21 | issue = 2 | pages = 117–125 | date = March 2006 | pmid = 16342227 | doi = 10.1002/hup.750 | s2cid = 23442056 }}</ref><ref name="pmid16460699">{{cite journal | vauthors = Gillman PK | title = A review of serotonin toxicity data: implications for the mechanisms of antidepressant drug action | journal = Biological Psychiatry | volume = 59 | issue = 11 | pages = 1046–1051 | date = June 2006 | pmid = 16460699 | doi = 10.1016/j.biopsych.2005.11.016 | s2cid = 12179122 }}</ref> This is in accordance with the fact that it is not a serotonin reuptake inhibitor or monoamine oxidase inhibitor, nor a serotonin receptor agonist.<ref name="pmid16342227" /><ref name="pmid16460699" /> There are no reports of serotonin syndrome in association with mirtazapine alone, and mirtazapine has not been found to cause serotonin syndrome in overdose.<ref name="pmid16342227" /><ref name="pmid16460699" /><ref name="pmid24228948">{{cite journal | vauthors = Berling I, Isbister GK | title = Mirtazapine overdose is unlikely to cause major toxicity | journal = Clinical Toxicology | volume = 52 | issue = 1 | pages = 20–24 | date = January 2014 | pmid = 24228948 | pmc = 3894718 | doi = 10.3109/15563650.2013.859264 }}</ref> 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.<ref name="pmid16342227" /><ref name="pmid19994622">{{cite journal | vauthors = Freijo Guerrero J, Tardón Ruiz de Gauna L, Gómez JJ, Aguilera Celorrio L | title = [Serotonin syndrome after administration of mirtazapine in a critical care unit] | language = es | journal = Revista Espanola de Anestesiologia y Reanimacion | volume = 56 | issue = 8 | pages = 515–516 | date = October 2009 | pmid = 19994622 | doi = 10.1016/s0034-9356(09)70444-x }}</ref><ref name="pmid20430060">{{cite journal | vauthors = Butler MC, Di Battista M, Warden M | title = Sertraline-induced serotonin syndrome followed by mirtazapine reaction | journal = Progress in Neuro-Psychopharmacology & Biological Psychiatry | volume = 34 | issue = 6 | pages = 1128–1129 | date = August 2010 | pmid = 20430060 | doi = 10.1016/j.pnpbp.2010.04.015 | s2cid = 20985498 }}</ref><ref name="pmid22752315">{{cite journal | vauthors = Decoutere L, De Winter S, Vander Weyden L, Spriet I, Schrooten M, Tournoy J, Fagard K | title = A venlafaxine and mirtazapine-induced serotonin syndrome confirmed by de- and re-challenge | journal = International Journal of Clinical Pharmacy | volume = 34 | issue = 5 | pages = 686–688 | date = October 2012 | pmid = 22752315 | doi = 10.1007/s11096-012-9666-7 | s2cid = 38692665 }}</ref>

====5-HT₃ receptor==== (R)-(–)-mirtazapine is a potent 5-HT₃ blocker.<ref name="Eisensamer">{{cite journal | vauthors = Eisensamer B, Rammes G, Gimpl G, Shapa M, Ferrari U, Hapfelmeier G, Bondy B, Parsons C, Gilling K, Zieglgänsberger W, Holsboer F, Rupprecht R | title = Antidepressants are functional antagonists at the serotonin type 3 (5-HT3) receptor | journal = Molecular Psychiatry | volume = 8 | issue = 12 | pages = 994–1007 | date = November 2003 | pmid = 14647397 | doi = 10.1038/sj.mp.4001314 }}</ref> It may relieve chemotherapy-related and advanced cancer-related nausea.<ref name="pmid17587360"/>

====H₁ receptor==== Mirtazapine is a very strong H₁ receptor antagonist and, as a result, it can cause powerful sedative and hypnotic effects.<ref name=Ant2001 /> A single 15&nbsp;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.<ref name="pmid23728612">{{cite journal | vauthors = Sato H, Ito C, Tashiro M, Hiraoka K, Shibuya K, Funaki Y, Iwata R, Matsuoka H, Yanai K | title = Histamine H₁ receptor occupancy by the new-generation antidepressants fluvoxamine and mirtazapine: a positron emission tomography study in healthy volunteers | journal = Psychopharmacology | volume = 230 | issue = 2 | pages = 227–234 | date = November 2013 | pmid = 23728612 | doi = 10.1007/s00213-013-3146-1 | s2cid = 3052216 }}</ref> After a short period of chronic treatment, however, the H₁ receptor tends to sensitize 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.<ref name="pmid9090576">{{cite journal | vauthors = Burrows GD, Kremer CM | title = Mirtazapine: clinical advantages in the treatment of depression | journal = Journal of Clinical Psychopharmacology | volume = 17 | issue = Suppl 1 | pages = 34S–39S | date = April 1997 | pmid = 9090576 | doi = 10.1097/00004714-199704001-00005 }}</ref>

===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.<ref>{{cite journal | vauthors = Zhu Y, Chen G, Zhang K, Chen C, Chen W, Zhu M, Jiang H | title = High-Throughput Metabolic Soft-Spot Identification in Liver Microsomes by LC/UV/MS: Application of a Single Variable Incubation Time Approach | journal = Molecules | volume = 27 | issue = 22 | page = 8058 | date = November 2022 | pmid = 36432161 | pmc = 9693510 | doi = 10.3390/molecules27228058 | doi-access = free }}</ref><ref name="A review of the pharmacological and"/> The overall elimination half-life is 20–40 hours, and this is independent of dosage.<ref name="pmid10885584" /> It is conjugated in the kidney for excretion in the urine, where 75% of the drug is excreted,<ref>{{cite book |vauthors = Al-Majed A, Bakheit AH, Alharbi RM, Abdel Aziz HA |title=Mirtazapine |journal=<!-- --> |series=Profiles of Drug Substances, Excipients and Related Methodology |date=1 January 2018 |volume=43 |pages=209–254 |doi=10.1016/bs.podrm.2018.01.002 |pmid=29678261 |isbn=978-0-12-815125-9 }}</ref> and about 15% is eliminated in feces.<ref name=Schatzberg/>{{rp|430}} Desmethylmirtazapine is an active metabolite of mirtazapine which is believed to contribute about 3-10% to the drug's overall effects and has a half-life of about 25 hours.<ref name="pmid10885584" />

Typical steady-state serum concentrations of mirtazapine range from 33 to 56 nmol/l after five daily doses of 7.5&nbsp;mg mirtazapine or 41 and 74 nmol/l after 15&nbsp;mg mirtazapine.<ref>{{cite journal | vauthors = Smith DF, Stork BS, Wegener G, Jakobsen S, Bender D, Audrain H, Jensen SB, Hansen SB, Rodell A, Rosenberg R | date = November 2007 | title = Receptor occupancy of mirtazapine determined by PET in healthy volunteers | journal = Psychopharmacology | volume = 195 | issue = 1 | pages = 131–138 | doi = 10.1007/s00213-007-0877-x | pmid = 17653532 }}</ref>

==Chemistry== Mirtazapine is a tetracyclic piperazinoazepine; mianserin was developed by the same team of organic chemists and mirtazapine differs from it via the addition of a nitrogen atom in one of the rings.<ref name=Schatzberg/>{{rp|429}}<ref>{{cite web|title=Mirtazapine label – Australia|url=http://secure.healthlinks.net.au/content/msd/pi.cfm?product=mkpavant|publisher=GuildLink, a wholly owned subsidiary company of the Pharmacy Guild of Australia.|date=27 May 2016|access-date=22 July 2017|archive-date=21 November 2018|archive-url=https://web.archive.org/web/20181121120001/http://secure.healthlinks.net.au/content/msd/pi.cfm?product=mkpavant|url-status=usurped}}</ref><ref>{{cite journal | vauthors = Kelder J, Funke C, De Boer T, Delbressine L, Leysen D, Nickolson V | title = A comparison of the physicochemical and biological properties of mirtazapine and mianserin | journal = The Journal of Pharmacy and Pharmacology | volume = 49 | issue = 4 | pages = 403–411 | date = April 1997 | pmid = 9232538 | doi = 10.1111/j.2042-7158.1997.tb06814.x | s2cid = 12270528 | doi-access = free }}</ref> 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 2-chloro-3-cyanopyridine (1) and 1-methyl-3-phenylpiperazine (2) to give cyano compound 3. Hydrolysis of the cyanide group to the corresponding carboxylic acid (4), reduction to the alcohol (5) allows for mirtazapine (6) to be synthesised via an acid mediated cyclisation.<ref>{{cite journal | doi = 10.1080/00304940709458595| title = Improved Synthesis of Mirtazapine| journal = Organic Preparations and Procedures International| volume = 39| issue = 4| pages = 399–402| year = 2007| vauthors = Srinivasa Rao DV, Dandala R, Handa VK, Sivakumaran M, Raghava Reddy AV, Naidu A | s2cid = 98056931}}</ref> center|thumb|955x955px|Route to mirtazapine.

==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.<ref name=Schatzberg>{{cite book| vauthors = Schatzberg AF | veditors = Schatzberg AF, Nemeroff CB |title=The American Psychiatric Publishing Textbook of Psychopharmacology|date=2009|publisher=American Psychiatric Pub.|location=Washington, D.C.|isbn=978-1-58562-309-9|edition=4th|chapter=Chapter 21: Mirtazapine}}</ref>{{rp|429}}<ref>{{cite journal| vauthors = Kaspersen FM, Van Rooij FA, Sperling EG, Wieringa JH |title=The synthesis of org 3770 labelled with 3H, 13C AND 14C|journal=Journal of Labelled Compounds and Radiopharmaceuticals|date=September 1989|volume=27|issue=9|pages=1055–1068|doi=10.1002/jlcr.2580270911}}</ref>

==Society and culture== thumb|right|A 15&nbsp;mg tablet of generic mirtazapine

===Generic names=== Mirtazapine is the English and French generic name of the drug and its {{abbrlink|INN|International Nonproprietary Name}}, {{abbrlink|USAN|United States Adopted Name}}, {{abbrlink|USP|United States Pharmacopeia}}, {{abbrlink|BAN|British Approved Name}}, {{abbrlink|DCF|Dénomination Commune Française}}, and {{abbrlink|JAN|Japanese Accepted Name}}.<ref name="IndexNominum2000">{{cite book|title=Index Nominum 2000: International Drug Directory|url=https://books.google.com/books?id=5GpcTQD_L2oC&pg=PA696|year=2000|publisher=Taylor & Francis|isbn=978-3-88763-075-1|pages=696–}}</ref><ref name="Drugs.com">{{cite web|url=https://www.drugs.com/international/mirtazapine.html|title=Mirtazapine - Drugs.com|access-date=14 August 2017|archive-date=17 November 2018|archive-url=https://web.archive.org/web/20181117063153/https://www.drugs.com/international/mirtazapine.html|url-status=live}}</ref><ref name="MortonHall2012">{{cite book| vauthors = Morton IK, Hall JM |title=Concise Dictionary of Pharmacological Agents: Properties and Synonyms|url=https://books.google.com/books?id=tsjrCAAAQBAJ&pg=PA183|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-94-011-4439-1|page=183}}</ref> Its generic name in Spanish, Italian, and Portuguese is mirtazapina and in German, Turkish and Swedish is mirtazapin.<ref name="IndexNominum2000" /><ref name="Drugs.com" />

===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, 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, Mirtanza, 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, Zamir, Zania, Zapex, Zapsy, Zestat, Zismirt, Zispin, Zuleptan, and Zulin.<ref name="Drugs.com" />

===Music=== Musician Hayley Williams wrote and released a song titled ''Mirtazapine'' describing her positive experience with the medication.<ref>{{cite web | vauthors = Chelosky D | date = July 23, 2025 | title = Hayley Williams Debuts New Song "Mirtazapine" On Nashville Public Radio | website = Stereogum | url = https://www.stereogum.com/2316741/hayley-williams-debuts-new-song-mirtazapine-on-nashville-public-radio | access-date = July 23, 2025 | archive-date = August 30, 2025 | archive-url = https://web.archive.org/web/20250830203139/https://www.stereogum.com/2316741/hayley-williams-debuts-new-song-mirtazapine-on-nashville-public-radio/ | url-status = live }}</ref>

==Research== The use of mirtazapine has been explored in several additional conditions: * Found ineffective for Sleep apnea/hypopnea<ref name="pmid19388881">{{cite journal | vauthors = Kohler M, Bloch KE, Stradling JR | title = Pharmacological approaches to the treatment of obstructive sleep apnoea | journal = Expert Opinion on Investigational Drugs | volume = 18 | issue = 5 | pages = 647–656 | date = May 2009 | pmid = 19388881 | doi = 10.1517/13543780902877674 | s2cid = 57089477 | url = https://www.zora.uzh.ch/id/eprint/28318/1/28318_manuscript.pdf | access-date = 23 December 2021 | archive-date = 12 April 2022 | archive-url = https://web.archive.org/web/20220412003252/https://www.zora.uzh.ch/id/eprint/28318/1/28318_manuscript.pdf }}</ref><ref name="pmid18548827">{{cite journal | vauthors = Marshall NS, Yee BJ, Desai AV, Buchanan PR, Wong KK, Crompton R, Melehan KL, Zack N, Rao SG, Gendreau RM, Kranzler J, Grunstein RR | title = Two randomized placebo-controlled trials to evaluate the efficacy and tolerability of mirtazapine for the treatment of obstructive sleep apnea | journal = Sleep | volume = 31 | issue = 6 | pages = 824–831 | date = June 2008 | pmid = 18548827 | pmc = 2442407 | doi = 10.1093/sleep/31.6.824 }}</ref> * Secondary symptoms of autistic spectrum conditions and other pervasive developmental disorders<ref name="pmid15584771">{{cite journal | vauthors = Masi G | title = Pharmacotherapy of pervasive developmental disorders in children and adolescents | journal = CNS Drugs | volume = 18 | issue = 14 | pages = 1031–1052 | year = 2004 | pmid = 15584771 | doi = 10.2165/00023210-200418140-00006 | s2cid = 25531695 }}</ref><ref name="pmid12589395">{{cite journal | vauthors = Marek GJ, Carpenter LL, McDougle CJ, Price LH | title = Synergistic action of 5-HT2A antagonists and selective serotonin reuptake inhibitors in neuropsychiatric disorders | journal = Neuropsychopharmacology | volume = 28 | issue = 2 | pages = 402–412 | date = February 2003 | pmid = 12589395 | doi = 10.1038/sj.npp.1300057 | doi-access = free }}</ref> * Antipsychotic-induced akathisia.<ref name="pmid19378382">{{cite journal | vauthors = Kumar R, Sachdev PS | title = Akathisia and second-generation antipsychotic drugs | journal = Current Opinion in Psychiatry | volume = 22 | issue = 3 | pages = 293–299 | date = May 2009 | pmid = 19378382 | doi = 10.1097/YCO.0b013e32832a16da | s2cid = 31506138 }}</ref><ref name="pmid18460588">{{cite journal | vauthors = Hieber R, Dellenbaugh T, Nelson LA | title = Role of mirtazapine in the treatment of antipsychotic-induced akathisia | journal = The Annals of Pharmacotherapy | volume = 42 | issue = 6 | pages = 841–846 | date = June 2008 | pmid = 18460588 | doi = 10.1345/aph.1K672 | s2cid = 19733585 }}</ref> * Drug withdrawal, dependence and detoxification<ref>{{cite journal | vauthors = Graves SM, Rafeyan R, Watts J, Napier TC | title = Mirtazapine, and mirtazapine-like compounds as possible pharmacotherapy for substance abuse disorders: evidence from the bench and the bedside | journal = Pharmacology & Therapeutics | volume = 136 | issue = 3 | pages = 343–353 | date = December 2012 | pmid = 22960395 | pmc = 3483434 | doi = 10.1016/j.pharmthera.2012.08.013 }}</ref> * Negative, depressive and cognitive symptoms of schizophrenia (as an adjunct)<ref>{{cite book | isbn = 978-94-007-5805-6 | title = Polypharmacy in Psychiatry Practice, Volume I | vauthors = Ritsner, MS | veditors = Ritsner MS | year = 2013 | publisher = Springer Science+Business Media Dordrecht | doi = 10.1007/978-94-007-5805-6 | s2cid = 7705779 }}</ref> * A case report has been published in which mirtazapine reduced visual hallucinations in a patient with Parkinson's disease psychosis (PDP).<ref>{{cite journal | vauthors = Tagai K, Nagata T, Shinagawa S, Tsuno N, Ozone M, Nakayama K | title = Mirtazapine improves visual hallucinations in Parkinson's disease: a case report | journal = Psychogeriatrics | volume = 13 | issue = 2 | pages = 103–107 | date = June 2013 | pmid = 23909968 | doi = 10.1111/j.1479-8301.2012.00432.x | s2cid = 1154368 | doi-access = free }}</ref> This is in alignment with recent findings that inverse agonists at the 5-HT_2A 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-HT_2A receptors.<ref name="Maudsley" /> * Eight case reports have been reported in five papers on the use of mirtazapine in the treatment of hives as of 2017.<ref>{{cite journal | vauthors = Eskeland S, Halvorsen JA, Tanum L | title = Antidepressants have Anti-inflammatory Effects that may be Relevant to Dermatology: A Systematic Review | journal = Acta Dermato-Venereologica | volume = 97 | issue = 8 | pages = 897–905 | date = August 2017 | pmid = 28512664 | doi = 10.2340/00015555-2702 | doi-access = free | hdl = 10852/63759 | hdl-access = free }}</ref> * Mirtazapine to alleviate severe breathlessness in patients with COPD or interstitial lung diseases (BETTER-B). Found ineffective and potentially harmful.<ref>{{cite journal |vauthors= Higginson IJ, Brown ST, Oluyase OO, May P, Maddocks M, Costantini M, Bajwah S, Normand C, Bausewein C, Simon T, Ryan K, Currow D, Johnson M, Hart S, Mather H, Krajnik M, Tanzi S, Ghirotto L, Bolton C, Janowiak P, Turola E, Jolley C, Murden G, Wilcock A, Farsides B, Brown JM | date=September 2024 |title= Mirtazapine to alleviate severe breathlessness in patients with COPD or interstitial lung diseases (BETTER-B). |journal=The Lancet Respiratory Medicine | volume=42 | doi=10.1016/S2213-2600(24)00187-5 | doi-access=free | pmid=39278621}}</ref>

==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 acute post-surgical pain and medical conditions like chronic kidney disease.<ref name="Dowling_2023">{{cite web | vauthors = Dowling PM, Foster D | title = Drugs That Affect Appetite in Monogastric Animals | date = 3 May 2023 | website = Merck Veterinary Manual | url = https://www.merckvetmanual.com/pharmacology/systemic-pharmacotherapeutics-of-the-digestive-system/drugs-that-affect-appetite-in-monogastric-animals | access-date = 5 July 2025 }}</ref> It is especially useful for treating combined poor appetite and nausea in cats and dogs.<ref>{{cite journal|title=Mirtazapine (Remeron)|website=Vin.com|url=http://www.veterinarypartner.com/Content.plx?P=A&A=2552|date=8 August 2017|vauthors=Gfeller R, Thomas M, Mayo I|access-date=12 January 2013|archive-date=6 December 2010|archive-url=https://web.archive.org/web/20101206073647/http://www.veterinarypartner.com/Content.plx?P=A|url-status=live}}</ref><ref>{{cite journal | vauthors = Agnew W, Korman R | title = Pharmacological appetite stimulation: rational choices in the inappetent cat | journal = Journal of Feline Medicine and Surgery | volume = 16 | issue = 9 | pages = 749–756 | date = September 2014 | pmid = 25146662 | doi = 10.1177/1098612X14545273 | s2cid = 37126352 | pmc = 11185246 }}</ref><ref name="Mirataz EPAR">{{cite web | title=Mirataz EPAR | website=European Medicines Agency | date=11 October 2019 | url=https://www.ema.europa.eu/en/medicines/veterinary/EPAR/mirataz | access-date=12 July 2020 | archive-date=29 October 2020 | archive-url=https://web.archive.org/web/20201029151621/https://www.ema.europa.eu/en/medicines/veterinary/EPAR/mirataz | url-status=live }}</ref><ref name="Mirataz FDA label">{{cite web | title=Mirataz- mirtazapine ointment | website=DailyMed | date=8 May 2020 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f4a55914-6b6e-4e81-a84c-3999aa7bd79e | access-date=12 July 2020 | archive-date=12 July 2020 | archive-url=https://web.archive.org/web/20200712223906/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f4a55914-6b6e-4e81-a84c-3999aa7bd79e | url-status=live }}</ref>

There are two options for administration: tablets given orally, and an ointment applied topically to the inner surface of the ear.<ref name="Mirataz EPAR" /><ref name="Mirataz FDA label" /> The most common side effects of the latter include local irritation or inflammation at the site where the ointment is applied and behavioural changes, such as increased meowing, hyperactivity, disoriented state, inability to coordinate muscle movements, lack of energy/weakness, attention-seeking, and aggression.<ref name="Mirataz EPAR" /><ref name="Mirataz FDA label" />

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