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Mirtazapine: Difference between revisions

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Mechanism of action of Mirtazapine and pharmacokinetics
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{{SummarySheet}}
{{SummarySheet}}
{{SubstanceBox/Mirtazapine}}
{{SubstanceBox/Mirtazapine}}
'''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).{{citation needed}}
'''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 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  
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  
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*[[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>
*[[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>{{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>
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).


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.


Mirtazapine is administered orally. Plasma protein binding is approximately 85%. Mirtazapine is extensively metabolized in the liver, primarily by demethylation and hydroxylation followed by glucuronide conjugation. The isoenzymes CYP2D6 and CYP1A2 are involved in the formation of the 8-hydroxy metabolite of mirtazapine and CYP3A is responsible for the formation of the N-desmethyl and N-oxide metabolite. Several unconjugated metabolites possess pharmacological activity but levels are very low in the plasma. The half-life of mirtazapine ranges from 20 to 40 hours. Elimination occurs primarily in the urine (75%) and to a lesser extent in the feces (15%).<ref name="Anttila2006" />,<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>.<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>
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==
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{{Preamble/SubjectiveEffects}}
{{Preamble/SubjectiveEffects}}
{{effects/base
{{effects/base
|{{effects/physical|
|{{effects/physical|
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*'''[[Effect::Increased music appreciation]]'''
*'''[[Effect::Increased music appreciation]]'''
*'''[[Effect::Irritability]]'''
*'''[[Effect::Irritability]]'''
*'''[[Effect::Emotion suppression]]''' - Mirtazapine has a dulling effect on emotions and it is typically difficult to express them.
*'''[[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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