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Mirtazapine: Difference between revisions
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'''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). | '''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> | ||
Mirtazapine was developed in the Netherlands and introduced in the United States in 1996.<ref> "REMERON (mirtazapine) tablet, film coated [Organon Pharmaceuticals USA]". DailyMed. Organon Pharmaceuticals USA. October 2012. Retrieved 24 October 2013.</ref> Its patent expired in 2004 and generic versions have been widely available since.<ref>Schatzberg, | Mirtazapine was developed in the Netherlands and introduced in the United States in 1996.<ref> "REMERON (mirtazapine) tablet, film coated [Organon Pharmaceuticals USA]". DailyMed. Organon Pharmaceuticals USA. October 2012. Retrieved 24 October 2013.</ref> Its patent expired in 2004 and generic versions have been widely available since.<ref name="Schatzberg">{{cite book | vauthors=((Schatzberg, A. F.)), ((Cole, J. O.)), ((DeBattista, C.)) | date= 2010 | title=Manual of clinical psychopharmacology | publisher=American Psychiatric Pub | volume=3 | edition=7th ed | isbn=9781585623778}}</ref> It is used primarily in the treatment of major depressive disorder and other mood disorders.<ref>{{cite journal | vauthors=((Gorman, J. M.)) | journal=The Journal of Clinical Psychiatry | title=Mirtazapine: clinical overview | volume=60 Suppl 17 | pages=9–13; discussion 46-48 | date= 1999 | issn=0160-6689}}</ref><ref>{{cite journal | journal=Expert Opinion on Pharmacotherapy | title=Review of the use of mirtazapine in the treatment of depression | url=https://informahealthcare.com/doi/abs/10.1517/14656566.2011.585459}}</ref> It has also been prescribed off-label for the treatment of | ||
generalized anxiety disorder,<ref>A Review of the Pharmacological and Clinical Profile of Mirtazapine | | 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>Itch: scratching more than the surface | | 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> | ||
Higher doses of mirtazapine (that exceed the recommended prescription dose) are reported to produce an unusual mixture of [[psychedelic]] and [[sedative]] effects. [[Subjective effects]] include [[sedation]] and mild-moderate versions of [[geometry|open and closed-eye visuals]], [[conceptual thinking]], and [[euphoria]]. | Higher doses of mirtazapine (that exceed the recommended prescription dose) are reported to produce an unusual mixture of [[psychedelic]] and [[sedative]] effects. [[Subjective effects]] include [[sedation]] and mild-moderate versions of [[geometry|open and closed-eye visuals]], [[conceptual thinking]], and [[euphoria]]. | ||
Mirtazapines has potential paradoxical effects concerning it's sedative effects. Anecdotal reports and studies suggest it's [[Sedation]] decreases as the dose increases. (7.5mg is more [[sedating]] than 15mg.) One theory suggests it has minor [[Stimulant]] effects that overpowers it's sedative effects. {{citation needed}} | |||
The toxicity and health risks of recreational mirtazapine use is not known. It is highly advised to use [[harm reduction practices]] if using this substance. | The toxicity and health risks of recreational mirtazapine use is not known. It is highly advised to use [[harm reduction practices]] if using this substance. | ||
==Chemistry== | ==Chemistry== | ||
Mirtazapine is a synthetic tetrahedral molecule of the piperazino-azepine and [[phenethylamine]] group of compounds. It is comprised of a fusion of pyridine, benzene, azepine, and piperazine rings. It is a tetracyclic antidepressant, named so because of their four-ring structure. Mirtazapine is the 6-aza analog of mianserin, which is pharmacologically similar in function. | Mirtazapine is a synthetic tetrahedral molecule of the piperazino-azepine and [[phenethylamine]] group of compounds. It is comprised of a fusion of pyridine, benzene, azepine, and piperazine rings. It is a tetracyclic antidepressant, named so because of their four-ring structure. Mirtazapine is the 6-aza analog of mianserin, which is pharmacologically similar in function. | ||
Mirtazapine enhances central adrenergic and serotonergic transmission, possibly by acting as an antagonist at central presynaptic alpha 2 adrenergic inhibitory autoreceptors and heteroreceptors. This agent is a potent antagonist of 5-hydroxytryptamine type 2 (5-HT2), 5-HT3, and histamine 1 (H1) receptors, and a moderate antagonist of peripheral alpha 1 adrenergic and muscarinic receptors.<ref> | Mirtazapine enhances central adrenergic and serotonergic transmission, possibly by acting as an antagonist at central presynaptic alpha 2 adrenergic inhibitory autoreceptors and heteroreceptors. This agent is a potent antagonist of 5-hydroxytryptamine type 2 (5-HT2), 5-HT3, and histamine 1 (H1) receptors, and a moderate antagonist of peripheral alpha 1 adrenergic and muscarinic receptors.<ref>{{Citation | title=NCI Thesaurus - Mirtazapine (Code C29265) | url=https://ncit.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&ns=NCI_Thesaurus&code=C29265}}</ref> | ||
==Pharmacology== | ==Pharmacology== | ||
Mirtazapine | 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<sub>2A</sub> receptor]]<ref name=" | *[[serotonin|5-HT<sub>2A</sub> receptor]]<ref name="Fernandez2005" /> | ||
*5-HT<sub>2B</sub> receptor<ref>{{cite journal | vauthors=((Boer, T. de)) | journal=The Journal of Clinical Psychiatry | title=The pharmacologic profile of mirtazapine | volume=57 Suppl 4 | pages=19–25 | date= 1996 | issn=0160-6689}}</ref> | |||
*5-HT<sub>2C</sub> receptor<ref name="Fernandez2005" /> | |||
*5-HT<sub>2B</sub> receptor<ref>The pharmacologic profile of mirtazapine | |||
*5-HT<sub>2C</sub> receptor <ref name=" | |||
*5-HT<sub>3</sub> receptor | *5-HT<sub>3</sub> receptor | ||
*5-HT<sub>7</sub> receptor | *5-HT<sub>7</sub> receptor | ||
*[[adrenaline|α<sub>1</sub>-adrenergic receptor]]<ref>Brunton, L | *[[adrenaline|α<sub>1</sub>-adrenergic receptor]]<ref name="Goodman2011">{{cite book | veditors=((Goodman, L. S.)), ((Brunton, L. L.)), ((Chabner, B.)), ((Knollmann, B. C.)) | date= 2011 | title=Goodman & Gilman’s pharmacological basis of therapeutics | publisher=McGraw-Hill | edition=12th ed | isbn=9780071624428}}</ref> | ||
*α<sub>2A</sub>-adrenergic receptor<ref>https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2010-PI-05345-3</ref> | *α<sub>2A</sub>-adrenergic receptor<ref name="TGAeBS">{{Citation | title=TGA eBS - Product and Consumer Medicine Information Licence | url=https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2010-PI-05345-3}}</ref> | ||
*α<sub>2B</sub>-adrenergic receptor<ref>Kennis | *α<sub>2B</sub>-adrenergic receptor<ref>{{cite journal | vauthors=((Kennis, L. E.)), ((Bischoff, F. P.)), ((Mertens, C. J.)), ((Love, C. J.)), ((Van den Keybus, F. A.)), ((Pieters, S.)), ((Braeken, M.)), ((Megens, A. A.)), ((Leysen, J. E.)) | journal=Bioorganic & Medicinal Chemistry Letters | title=New 2-substituted 1,2,3,4-tetrahydrobenzofuro[3,2-c]pyridine having highly active and potent central alpha 2-antagonistic activity as potential antidepressants | volume=10 | issue=1 | pages=71–74 | date=3 January 2000 | issn=0960-894X | doi=10.1016/s0960-894x(99)00591-0}}</ref> | ||
New 2-substituted 1,2,3,4-tetrahydrobenzofuro[3,2-c]pyridine having highly active and potent central alpha 2-antagonistic activity as potential antidepressants. | *α<sub>2C</sub>-adrenergic receptor<ref name="TGAeBS" /> | ||
*H<sub>1</sub> receptor<ref>{{cite journal | vauthors=((Wikström, H. V.)), ((Mensonides-Harsema, M. M.)), ((Cremers, T. I. F. H.)), ((Moltzen, E. K.)), ((Arnt, J.)) | journal=Journal of Medicinal Chemistry | title=Synthesis and Pharmacological Testing of 1,2,3,4,10,14b-Hexahydro-6-methoxy-2-methyldibenzo[ c , f ]pyrazino[1,2- a ]azepin and Its Enantiomers in Comparison with the Two Antidepressants Mianserin and Mirtazapine | volume=45 | issue=15 | pages=3280–3285 | date=1 July 2002 | url=https://pubs.acs.org/doi/10.1021/jm010566d | issn=0022-2623 | doi=10.1021/jm010566d}}</ref> | |||
*α<sub>2C</sub>-adrenergic receptor<ref | *[[acetylcholine|mACH receptors]]<ref name="Goodman2011" /> | ||
*H<sub>1</sub> receptor<ref>Synthesis and Pharmacological Testing of 1,2,3,4,10,14b-Hexahydro-6-methoxy-2-methyldibenzo[c,f]pyrazino[1,2-a]azepin and Its Enantiomers in Comparison with the Two Antidepressants Mianserin and Mirtazapine | | |||
*[[acetylcholine|mACH receptors]]<ref | |||
While mirtazapine has some affinity for the 5-HT<sub>2A</sub> receptor, it acts as an [[antagonist]]<ref | While mirtazapine has some affinity for the 5-HT<sub>2A</sub> receptor, it acts as an [[antagonist]]<ref name="Anttila2006" /> thus it is unlikely that this mechanism is responsible for its [[psychedelic]] and [[deliriant]] effects. | ||
Additionally, Mirtazapine has also been observed to indirectly agonize the following GCPR in humans: | Additionally, Mirtazapine has also been observed to indirectly agonize the following GCPR in humans: | ||
*[[Opioid]] receptor κ<sub>3</sub><ref>Schreiber, S., Rigai, T., Katz, Y., | *[[Opioid]] receptor κ<sub>3</sub><ref>{{cite journal | vauthors=((Schreiber, S.)), ((Rigai, T.)), ((Katz, Y.)), ((Pick, C. G.)) | journal=Brain Research Bulletin | title=The antinociceptive effect of mirtazapine in mice is mediated through serotonergic, noradrenergic and opioid mechanisms | volume=58 | issue=6 | pages=601–605 | date= September 2002 | url=https://linkinghub.elsevier.com/retrieve/pii/S0361923002008250 | issn=03619230 | doi=10.1016/S0361-9230(02)00825-0}}</ref> | ||
Mirtazapine has also been found to modulate the κ<sub>3</sub> opioid receptor, supporting the claim that mirtazapine causes pain relief<ref>Dapoigny M, Abitbol | Mirtazapine has also been found to modulate the κ<sub>3</sub> opioid receptor, supporting the claim that mirtazapine causes pain relief<ref>{{cite journal | vauthors=((Dapoigny, M.)), ((Abitbol, J. L.)), ((Fraitag, B.)) | journal=Digestive Diseases and Sciences | title=Efficacy of peripheral kappa agonist fedotozine versus placebo in treatment of irritable bowel syndrome. A multicenter dose-response study | volume=40 | issue=10 | pages=2244–2249 | date= October 1995 | issn=0163-2116 | doi=10.1007/BF02209014}}</ref> and adds to the [[sedative]] and [[hallucinogenic]] effects of mirtazapine<ref>{{cite journal | vauthors=((Pande, A. C.)), ((Pyke, R. E.)), ((Greiner, M.)), ((Wideman, G. L.)), ((Benjamin, R.)), ((Pierce, M. W.)) | journal=Clinical Neuropharmacology | title=Analgesic efficacy of enadoline versus placebo or morphine in postsurgical pain | volume=19 | issue=5 | pages=451–456 | date= October 1996 | issn=0362-5664 | doi=10.1097/00002826-199619050-00009}}</ref><ref>{{cite journal | vauthors=((Rimoy, G. H.)), ((Wright, D. M.)), ((Bhaskar, N. K.)), ((Rubin, P. C.)) | journal=European Journal of Clinical Pharmacology | title=The cardiovascular and central nervous system effects in the human of U-62066E. A selective opioid receptor agonist | volume=46 | issue=3 | pages=203–207 | date= 1994 | issn=0031-6970 | doi=10.1007/BF00192549}}</ref>. This even may explain mirtazapine's withdrawal/discontinuation effects as well as its promotion of diuresis and a possible increase in food intake (usually resulting in weight gain). | ||
Efficacy of peripheral kappa agonist fedotozine versus placebo in treatment of irritable bowel syndrome. A multicenter dose-response study | |||
Analgesic efficacy of enadoline versus placebo or morphine in postsurgical pain | |||
The cardiovascular and central nervous system effects in the human of U-62066E. A selective opioid receptor agonist | |||
It should be noted that although some of these effects are observed in those who take mirtazapine recreationally (or one off dosing) most neurophysiological effects are observed in those with on-going use (15, 30 and 45 mg daily prescribed for depression, etc) due to a maintained level of mirtazapine in the body. | It should be noted that although some of these effects are observed in those who take mirtazapine recreationally (or one off dosing) most neurophysiological effects are observed in those with on-going use (15, 30 and 45 mg daily prescribed for depression, etc) due to a maintained level of mirtazapine in the body. | ||
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 | 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> | ||
==Subjective effects== | ==Subjective effects== | ||
| Line 61: | Line 50: | ||
{{Preamble/SubjectiveEffects}} | {{Preamble/SubjectiveEffects}} | ||
{{effects/base | {{effects/base | ||
|{{effects/physical| | |{{effects/physical| | ||
| Line 95: | Line 85: | ||
*'''[[Effect::Increased music appreciation]]''' | *'''[[Effect::Increased music appreciation]]''' | ||
*'''[[Effect::Irritability]]''' | *'''[[Effect::Irritability]]''' | ||
*'''[[Effect::Emotion suppression]]''' - Mirtazapine | *'''[[Effect::Emotion suppression]]''' - Mirtazapine can have a dulling effect on emotions and it is sometimes difficult to express them. | ||
*'''[[Effect::Anxiety suppression]]''' - This effect is much stronger and more rapidly acting than that of SSRIs. | *'''[[Effect::Anxiety suppression]]''' - This effect is much stronger and more rapidly acting than that of SSRIs. | ||
}} | }} | ||
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===Overdose=== | ===Overdose=== | ||
Mirtazapine is considered to be relatively safe in the event of an [[overdose]],<ref>Taylor, D | Mirtazapine is considered to be relatively safe in the event of an [[overdose]],<ref>{{cite book | veditors=((Taylor, D.)), ((Paton, C.)), ((Kapur, S.)) | date= 2012 | title=The Maudsley prescribing guidelines in psychiatry | publisher=Wiley | edition=11. ed | isbn=9780470979488}}</ref> although it is considered slightly more toxic in overdose than most of the SSRIs (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 = 238–50 | date = December 2008 | pmid = 19031375 | pmc = 3550116 | doi = 10.1007/bf03161207 | url = https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3550116/pdf/13181_2009_Article_BF03161207.pdf | format = PDF }}</ref> Unlike the TCAs, mirtazapine showed no significant cardiovascular adverse effects at 7 to 22 times the maximum recommended dose.<ref>{{cite journal | vauthors=((Fawcett, J.)), ((Barkin, R. L.)) | journal=Journal of Affective Disorders | title=Review of the results from clinical studies on the efficacy, safety and tolerability of mirtazapine for the treatment of patients with major depression | volume=51 | issue=3 | pages=267–285 | date=1 December 1998 | url=https://www.sciencedirect.com/science/article/pii/S0165032798002249 | issn=0165-0327 | doi=10.1016/S0165-0327(98)00224-9}}</ref> Case reports of overdose with as much as 30 to 50 times the standard dose described the drug as relatively nontoxic, compared to TCAs.<ref name="pmid9807651">{{cite journal | vauthors = Holzbach R, Jahn H, Pajonk FG, Mähne C | title = Suicide attempts with mirtazapine overdose without complications | journal = Biological Psychiatry | volume = 44 | issue = 9 | pages = 925–6 | date = November 1998 | pmid = 9807651 | doi = 10.1016/S0006-3223(98)00081-X }}{{Unreliable medical source|date=October 2011}}</ref><ref name="pmid9861579">{{cite journal | vauthors = Retz W, Maier S, Maris F, Rösler M | title = Non-fatal mirtazapine overdose | journal = International Clinical Psychopharmacology | volume = 13 | issue = 6 | pages = 277–9 | date = November 1998 | pmid = 9861579 | doi = 10.1097/00004850-199811000-00007 }}{{Unreliable medical source|date=October 2011}}</ref> | ||
Twelve reported fatalities 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}} in {{cite journal |doi=10.1080/15563650902952273 |title=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 }}</ref><ref>{{cite book | author = 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). This is similar to that observed with SSRIs.<ref name="bmj325">{{cite journal | vauthors = Buckley NA, McManus PR | title = Fatal toxicity of serotoninergic and other antidepressant drugs: analysis of United Kingdom mortality data | journal = BMJ | volume = 325 | issue = 7376 | pages = 1332–3 | date = December 2002 | pmid = 12468481 | pmc = 137809 | doi = 10.1136/bmj.325.7376.1332 }}{{Unreliable medical source|date=October 2011}}</ref> | Twelve reported fatalities 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}} in {{cite journal |doi=10.1080/15563650902952273 |title=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 }}</ref><ref>{{cite book | author = 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). This is similar to that observed with SSRIs.<ref name="bmj325">{{cite journal | vauthors = Buckley NA, McManus PR | title = Fatal toxicity of serotoninergic and other antidepressant drugs: analysis of United Kingdom mortality data | journal = BMJ | volume = 325 | issue = 7376 | pages = 1332–3 | date = December 2002 | pmid = 12468481 | pmc = 137809 | doi = 10.1136/bmj.325.7376.1332 }}{{Unreliable medical source|date=October 2011}}</ref> | ||