Mirtazapine: Difference between revisions

'''Mirtazapine''' (trade name '''Remeron''', among others) is an [[psychoactive class::antidepressant]] substance of the [[Chemical class::piperazinoazepine]] class. At high doses, it has been reported to act as an atypical [[psychedelic]] and [[sedative]]. It is classified as a noradrenergic and specific serotonergic antidepressant (NaSSA).<ref>Roland A. Carlstedt (14 December 2009). ''Handbook of Integrative Clinical Psychology, Psychiatry, and Behavioral Medicine: Perspectives, Practices, and Research''. Springer Publishing Company. p. 290. [[ISBN (identifier)|ISBN]] [[Special:BookSources/978-0-8261-1094-7|<bdi>978-0-8261-1094-7</bdi>]]. Retrieved 23 April 2012.</ref>

generalized anxiety disorder,<ref name="Anttila2006">{{cite journal | vauthors=((Anttila, S. A. K.)), ((Leinonen, E. V. J.)) | journal=CNS Drug Reviews | title=A Review of the Pharmacological and Clinical Profile of Mirtazapine | volume=7 | issue=3 | pages=249–264 | date=7 June 2006 | url=https://onlinelibrary.wiley.com/doi/10.1111/j.1527-3458.2001.tb00198.x | issn=1080563X | doi=10.1111/j.1527-3458.2001.tb00198.x}}</ref> social anxiety disorder,<ref name="Croom2009">{{cite journal | vauthors=((Croom, K. F.)), ((Perry, C. M.)), ((Plosker, G. L.)) | journal=CNS Drugs | title=Mirtazapine | volume=23 | issue=5 | pages=427–452 | date=1 May 2009 | url=https://doi.org/10.2165/00023210-200923050-00006 | issn=1179-1934 | doi=10.2165/00023210-200923050-00006}}</ref><ref>{{cite journal | vauthors=((Muehlbacher, M.)), ((Nickel, M. K.)), ((Nickel, C.)), ((Kettler, C.)), ((Lahmann, C.)), ((Gil, F. P.)), ((Leiberich, P. K.)), ((Rother, N.)), ((Bachler, E.)), ((Fartacek, R.)), ((Kaplan, P.)), ((Tritt, K.)), ((Mitterlehner, F.)), ((Anvar, J.)), ((Rother, W. K.)), ((Loew, T. H.)), ((Egger, C.)) | journal=Journal of Clinical Psychopharmacology | title=Mirtazapine Treatment of Social Phobia in Women: A Randomized, Double-Blind, Placebo-Controlled Study | volume=25 | issue=6 | pages=580–583 | date= December 2005 | url=http://journals.lww.com/00004714-200512000-00015 | issn=0271-0749 | doi=10.1097/01.jcp.0000186871.04984.8d}}</ref> obsessive-compulsive disorder,<ref name="Croom2009" /><ref>Mirtazapine Treatment of Obsessive-Compulsive Disorder | http://journals.lww.com/psychopharmacology/Citation/2001/10000/Mirtazapine_Treatment_of_Obsessive_Compulsive.16.aspx</ref> panic disorder,<ref name="Croom2009" /><ref name="Carpenter1999">{{cite journal | vauthors=((Carpenter, L.)), ((Leon, Z.)), ((Yasmin, S.)), ((Price, L.)) | journal=Annals of Clinical Psychiatry | title=Clinical Experience with Mirtazapine in the Treatment of Panic Disorder | volume=11 | issue=2 | pages=81–86 | date=1 June 1999 | issn=1040-1237 | doi=10.3109/10401239909147053}}</ref> post-traumatic stress disorder,<ref name="Croom2009" /> low appetite,<ref>{{cite journal | vauthors=((Landowski, J.)) | journal=Psychiatria Polska | title=[Mirtazapine--an antidepressant] | volume=36 | issue=6 Suppl | pages=125–130 | date= December 2002 | issn=0033-2674}}</ref><ref>{{cite journal | vauthors=((Chinuck, R. S.)), ((Fortnum, H.)), ((Baldwin, D. R.)) | journal=Journal of Human Nutrition and Dietetics | title=Appetite stimulants in cystic fibrosis: a systematic review | volume=20 | issue=6 | pages=526–537 | date= December 2007 | url=https://onlinelibrary.wiley.com/doi/10.1111/j.1365-277X.2007.00824.x | issn=0952-3871 | doi=10.1111/j.1365-277X.2007.00824.x}}</ref><ref>{{cite journal | journal=Expert Review of Anticancer Therapy | title=Management of symptons associated with advanced cancer: olanzapine and mirtazapine | url=https://informahealthcare.com/doi/abs/10.1586/14737140.2.4.365}}</ref> insomnia,<ref>{{cite journal | vauthors=((Hartmann, P. M.)) | journal=American Family Physician | title=Mirtazapine: a newer antidepressant | volume=59 | issue=1 | pages=159–161 | date=1 January 1999 | issn=0002-838X}}</ref><ref>{{cite journal | vauthors=((Jindal, R. D.)) | journal=CNS Drugs | title=Insomnia in Patients with Depression | volume=23 | issue=4 | pages=309–329 | date=1 April 2009 | url=https://doi.org/10.2165/00023210-200923040-00004 | issn=1179-1934 | doi=10.2165/00023210-200923040-00004}}</ref> nausea/vomiting,<ref>{{cite journal | vauthors=((Nutt, D. J.)) | journal=Human Psychopharmacology: Clinical and Experimental | title=Tolerability and safety aspects of mirtazapine | volume=17 | issue=S1 | pages=S37–S41 | date= June 2002 | url=https://onlinelibrary.wiley.com/doi/10.1002/hup.388 | issn=0885-6222 | doi=10.1002/hup.388}}</ref><ref name="Li2011">{{cite journal | vauthors=((Li, T.-C.)), ((Shiah, I.-S.)), ((Sun, C.-J.)), ((Tzang, R.-F.)), ((Huang, K.-C.)), ((Lee, W.-K.)) | journal=The Journal of ECT | title=Mirtazapine Relieves Post-Electroconvulsive Therapy Headaches and Nausea: A Case Series and Review of the Literature | volume=27 | issue=2 | pages=165–167 | date= June 2011 | url=https://journals.lww.com/00124509-201106000-00016 | issn=1095-0680 | doi=10.1097/YCT.0b013e3181e63346}}</ref><ref>{{cite journal | vauthors=((Kast, R. E.)), ((Foley, K. F.)) | journal=European Journal of Cancer Care | title=Cancer chemotherapy and cachexia: mirtazapine and olanzapine are 5-HT3 antagonists with good antinausea effects | volume=16 | issue=4 | pages=351–354 | date= July 2007 | url=https://onlinelibrary.wiley.com/doi/10.1111/j.1365-2354.2006.00760.x | issn=0961-5423 | doi=10.1111/j.1365-2354.2006.00760.x}}</ref>  

itching,<ref>{{cite journal | vauthors=((Twycross, R.)) | journal=QJM | title=Itch: scratching more than the surface | volume=96 | issue=1 | pages=7–26 | date=1 January 2003 | url=https://academic.oup.com/qjmed/article-lookup/doi/10.1093/qjmed/hcg002 | issn=14602393 | doi=10.1093/qjmed/hcg002}}</ref><ref>{{cite journal | vauthors=((Greaves, M. W.)) | journal=Dermatologic Therapy | title=Itch in systemic disease: therapeutic options: Itch in systemic disease | volume=18 | issue=4 | pages=323–327 | date=17 November 2005 | url=https://onlinelibrary.wiley.com/doi/10.1111/j.1529-8019.2005.00036.x | issn=13960296 | doi=10.1111/j.1529-8019.2005.00036.x}}</ref> and headaches and migraines.<ref name="Li2011" /><ref>{{cite journal | vauthors=((Colombo, B.)), ((Annovazzi, P. O. L.)), ((Comi, G.)) | journal=Neurological Sciences | title=Therapy of primary headaches: the role of antidepressants | volume=25 | issue=3 | pages=s171–s175 | date=1 October 2004 | url=https://doi.org/10.1007/s10072-004-0280-x | issn=1590-3478 | doi=10.1007/s10072-004-0280-x}}</ref><ref>{{cite journal | vauthors=((Tajti, J.)), ((Almási, J.)) | journal=Neuropsychopharmacologia Hungarica: A Magyar Pszichofarmakologiai Egyesulet Lapja = Official Journal of the Hungarian Association of Psychopharmacology | title=[Effects of mirtazapine in patients with chronic tension-type headache. Literature review] | volume=8 | issue=2 | pages=67–72 | date= June 2006 | issn=1419-8711}}</ref>

Mirtazapine inhibits presynaptic serotonin (5-HT)-2 and alpha-2 adrenergic auto- and hetero-receptors, thereby increasing serotonergic and noradrenergic neurotransmission. The increased amount of 5-HT released interacts with postsynaptic 5-HT1 receptors, which may be relevant to the antidepressant effects of the drug. The affinity of mirtazapine for central alpha-2 adrenoreceptors is 10 times higher than for peripheral receptors, resulting in fewer peripheral effects related to increased blood pressure. Mirtazapine is an antagonist at postsynaptic 5-HT2A, 5-HT2C, and 5-HT3 receptors. The blockade of these receptors may result in a lower incidence of certain adverse effects (e.g., anxiety, insomnia, nausea) than occurs with antidepressants that do not antagonize these receptors. Mirtazapine significantly antagonizes histamine H1 receptors at low doses, and this activity is associated with sedation and appetite stimulation. Higher doses have a greater effect on norepinephrine release relative to antihistamine effects, which may offset the sedative potential and appetite stimulation observed at low doses. Mirtazapine has muscarinic antagonist properties, which may be associated with xerostomia, constipation, and other anticholinergic effects. Orthostatic hypotension is the result of the peripheral alpha-1 adrenergic antagonism of the drug. Mirtazapine does not have clinically significant receptor affinity for dopamine, 5-HT1A, or 5-HT1B, and has no effects on the central reuptake of either norepinephrine or serotonin.:<ref name="Fernandez2005">{{cite journal | vauthors=((Fernández, J.)), ((Alonso, J. M.)), ((Andrés, J. I.)), ((Cid, J. M.)), ((Díaz, A.)), ((Iturrino, L.)), ((Gil, P.)), ((Megens, A.)), ((Sipido, V. K.)), ((Trabanco, A. A.)) | journal=Journal of Medicinal Chemistry | title=Discovery of New Tetracyclic Tetrahydrofuran Derivatives as Potential Broad-Spectrum Psychotropic Agents | volume=48 | issue=6 | pages=1709–1712 | date=1 March 2005 | url=https://pubs.acs.org/doi/10.1021/jm049632c | issn=0022-2623 | doi=10.1021/jm049632c}}</ref><ref>{{cite journal | vauthors=((Boer, Th. de)), ((Maura, G.)), ((Raiteri, M.)), ((Vos, C. J. de)), ((Wieringa, J.)), ((Pinder, R. M.)) | journal=Neuropharmacology | title=Neurochemical and autonomic pharmacological profiles of the 6-aza-analogue of mianserin, org 3770 and its enantiomers | volume=27 | issue=4 | pages=399–408 | date=1 April 1988 | url=https://www.sciencedirect.com/science/article/pii/0028390888901499 | issn=0028-3908 | doi=10.1016/0028-3908(88)90149-9}}</ref>

*[[serotonin|5-HT_2A receptor]]<ref name="Fernandez2005" />

*5-HT_2C receptor<ref name="Fernandez2005" />

*α_2C-adrenergic receptor<ref name="TGAeBS" />

*[[acetylcholine|mACH receptors]]<ref name="Goodman2011" />

While mirtazapine has some affinity for the 5-HT_2A receptor, it acts as an [[antagonist]]<ref name="Anttila2006" /> thus it is unlikely that this mechanism is responsible for its [[psychedelic]] and [[deliriant]] effects.

The oral bioavailability of mirtazapine is about 50%. It is found mostly bound to plasma proteins, about 85%. It is metabolized primarily in the liver by demethylation and hydroxylation via cytochrome P450 enzymes, CYP1A2, CYP2D6, CYP3A4.<ref name="Anttila2006" /> One of its major metabolites is desmethylmirtazapine. The overall elimination half-life is 20–40 hours. It is conjugated in the kidney for excretion in the urine, where 75% of the drug is excreted,<ref>{{cite journal | vauthors=((Al-Majed, A.)), ((Bakheit, A. H.)), ((Alharbi, R. M.)), ((Abdel Aziz, H. A.)) | journal=Profiles of Drug Substances, Excipients, and Related Methodology | title=Mirtazapine | volume=43 | pages=209–254 | date= 2018 | issn=1871-5125 | doi=10.1016/bs.podrm.2018.01.002}}</ref>  and about 15% is eliminated in feces.<ref>{{cite book | veditors=((Schatzberg, A. F.)), ((Nemeroff, C. B.)) | date= 2009 | title=The American Psychiatric Publishing textbook of psychopharmacology | publisher=American Psychiatric Pub | edition=4th ed | isbn=9781585623099}}</ref>

*'''[[Effect::Emotion suppression]]''' - Mirtazapine can have a dulling effect on emotions and it is sometimes difficult to express them.