Mirtazapine

Summary sheet: Mirtazapine
Mirtazapine
Mirtazapine.svg
Chemical Nomenclature
Common names Avanza, Axit, Mirtaz, Mirtazon, Remeron, Zispin
Substitutive name Mirtazapine
Systematic name (±)-2-Methyl-1,2,3,4,10,14b-hexahydropyrazino[2,1-a]pyrido[2,3-c][2]benzazepine
Class Membership
Psychoactive class Deliriant / Depressant
Chemical class Piperazinoazepine
Routes of Administration

WARNING: Always start with lower doses due to differences between individual body weight, tolerance, metabolism, and personal sensitivity. See responsible use section.



⇣ Oral
Dosage
Bioavailability 50%[1]
Threshold 3.5 mg
Light 70 - 130 mg
Common 130 - 190 mg
Strong 190 - 250 mg
Heavy 250 mg +
Duration
Total 14 - 24 hours
Onset 15 - 30 minutes
Peak 90 - 180 minutes
Offset 2 - 6 hours
After effects up to 24 hours









DISCLAIMER: PW's dosage information is gathered from users and resources for educational purposes only. It is not a recommendation and should be verified with other sources for accuracy.

Interactions
Antidepressants

Mirtazapine (trade name Remeron, among others) is an antidepressant substance of the 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 was developed in the Netherlands and introduced in the United States in 1996.[2] Its patent expired in 2004 and generic versions have been widely available since.[3] It is used primarily in the treatment of major depressive disorder and other mood disorders.[4][5] It has also been prescribed off-label for the treatment of generalized anxiety disorder,[6] social anxiety disorder,[7][8] obsessive-compulsive disorder,[7][9] panic disorder,[7][10] post-traumatic stress disorder,[7] low appetite,[11][12][13] insomnia,[14][15] nausea/vomiting,[16][17][18] itching,[19][20] and headaches and migraines.[17][21][22]

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 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.

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 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.[23]

Pharmacology

Mirtazapine acts as an antagonist/inverse agonist upon the following receptors:[24][25]

While mirtazapine has some affinity for the 5-HT2A receptor, it acts as an antagonist[6] 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:

Mirtazapine has also been found to modulate the κ3 opioid receptor, supporting the claim that mirtazapine causes pain relief[32] and adds to the sedative and hallucinogenic effects of mirtazapine[33][34]. 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.

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.[6] 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,[35] and about 15% is eliminated in feces.[36]

Subjective effects

Although mirtazapine exhibits almost exclusively psychedelic effects, the hallucinations that accompany it do have distinctively deliriant-like effects. For example, they are often delirious in their believability and rarely comprised of condensed visual geometry. Instead they tend to be solid and extremely realistic in appearance.

The mental processes, thought patterns and general head space experienced during a high dose mirtazapine experience is one that is typically described to be completely devoid of insight. In contrast to many other substances with hallucinogenic properties, it produces no introspection, personal problem solving or creativity enhancing effects; for this reason it is generally reported that mirtazapine holds no therapeutic potential when used as a hallucinogen.

Disclaimer: The effects listed below cite the Subjective Effect Index (SEI), an open research literature based on anecdotal user reports and the personal analyses of PsychonautWiki contributors. As a result, they should be viewed with a healthy degree of skepticism.

It is also worth noting that these effects will not necessarily occur in a predictable or reliable manner, although higher doses are more liable to induce the full spectrum of effects. Likewise, adverse effects become increasingly likely with higher doses and may include addiction, severe injury, or death ☠.

Physical effects
 

    • Sedation - In terms of energy level alterations, mirtazapine is extremely sedating and often results in an overwhelmingly lethargic state. This causes users to suddenly feel as if they are extremely sleep deprived and have not slept for days, forcing them to sit down and generally feel as if they are constantly on the verge of passing out instead of engaging in physical activities. This sense of sleep deprivation increases proportional to dosage and eventually becomes powerful enough to force a person into complete unconsciousness. It is a state which often leaves people feeling extremely lethargic and tired the following day.
    • Spontaneous bodily sensations - The "body high" of mirtazapine can be described as a pleasurable, warm, soft and all-encompassing tingling sensation. This maintains a consistent presence that steadily rises with the onset and hits its limit once the peak has been reached and is not capable of becoming anything but mildly euphoric even at high dosages. This is accompanied by strange but mild throbbing or aching sensations.
    • Tactile hallucination - Unique tactile hallucinations are commonly felt within this substance. These can be described as bizarrely structured vibrations and pulsations that spontaneously manifest themselves across the skin at various locations and propagate outwards for a short distance from its center.
    • Changes in felt gravity
    • Motor control loss - If physical activities such as walking are forcibly engaged in, a distinct but not completely incapacitating loss of motor control is noticed as well as the consistent feeling that you are walking on top of a trampoline and not a normal solid floor.
    • Appetite enhancement - The above components are also accompanied by an intense appetite enhancement that is identical in strength to “the munchies” experienced with cannabis.[37]
    • Constipation
    • Dizziness
    • Dry mouth
    • Bronchodilation - This can cause swallowing to be extremely difficult and uncomfortable, as with some other anticholinergics such as diphenhydramine. As with diphenhydramine, it is most prominent during the onset phase of the experience and often fades away as the peak sets in.
    • Muscle relaxation
    • Restless legs - This effect is considered slightly less apparent than it is with diphenhydramine.
    • Nausea suppression

Auditory effects
 

Cognitive effects
 

Visual effects
 

  • Distortions

    Geometry

    In terms of complexity, the visual geometry found within high dose mirtazapine trips can be said to be completely on par with that of LSD or psilocin. It can be comprehensively described as intricate in complexity, abstract in style, structured in organization, equally organic and synthetic in style, dimly lit in lighting, monotone is scheme, glossy in shading, equal in sharp and soft edges, large in size, fast in speed, smooth in motion, equal in rounded and angular corners, non-immersive in depth and consistent in intensity.

    At higher dosages, Level 8A and Level 8B are not present simply because the sedating effects are too overwhelming to allow people to remain conscious at such a high level. Many users report an almost menacing feeling, following a sinister and ominous style with a colour scheme that generally consists of greys and blues.

    Hallucinatory states


Combination effects

  • Cannabis - When mirtazapine is combined with cannabis, the euphoric and visual effects are greatly potentiated.
  • Psychedelics - Due to mirtazapines action as a 5-HT2A antagonist, it can help reduce the intensity or "abort" a bad trip

Experience reports

Anecdotal reports which describe the effects of this compound within our experience index include:

Additional experience reports can be found here:

Toxicity and harm potential

 
This document, provided with prescription mirtazapine, contains detailed information regrading its toxicity and harm potential.
Further information: Responsible use § Hallucinogens

Mirtazapine is not known to cause brain damage, and has extremely low toxicity relative to dose. Similar to other psychedelic drugs, there are relatively few physical side effects associated with mirtazapine exposure. Various studies have shown that in reasonable doses in a careful context, it presents no negative cognitive, psychiatric or toxic physical consequences of any sort.

Dependence and abuse potential

Mirtazapine is not habit-forming when used as a hallucinogen and the desire to use it can actually decrease with use. It is most often self-regulating.

Tolerance to the effects of mirtazapine are built almost immediately after ingestion. After that, it takes about 3 days for the tolerance to be reduced to half and 7 days to be back at baseline (in the absence of further consumption).

Overdose

Mirtazapine is considered to be relatively safe in the event of an overdose,[38] although it is considered slightly more toxic in overdose than most of the SSRIs (except citalopram).[39] Unlike the TCAs, mirtazapine showed no significant cardiovascular adverse effects at 7 to 22 times the maximum recommended dose.[40] Case reports of overdose with as much as 30 to 50 times the standard dose described the drug as relatively nontoxic, compared to TCAs.[41][42]

Twelve reported fatalities have been attributed to mirtazapine overdose.[43][44] 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.[45]

It is strongly recommended that one use harm reduction practices when using this substance.

Dangerous interactions

    • Antidepressants - Different types of antidepressants can cause adverse effects as well as possible serotonin syndrome when mixed.

Legal status

 

This legality section is a stub.

As such, it may contain incomplete or wrong information. You can help by expanding it.

Mirtazapine is legally approved for medical purposes worldwide. However, it is illegal to sell and possess in most countries without a prescription.

  • Switzerland: Mirtazapine is listed as a "Abgabekategorie B" pharmaceutical, which generally requires a prescription.[citation needed]
  • Turkey: Mirtazapine is classed as anti-depressant so it is prescription only drug[citation needed] but the law is often unenforced.
  • United Kingdom: Mirtazapine is a licensed prescription-only medicine (POM) in the United Kingdom.[46] It is not a criminal offence to possess this medicine without a valid prescription. This medicine can legally be obtained with a valid prescription or through legal import of the medicine for personal use as outlined in Section 13 of the Medicines Act 1968.[47]

See also

External links

Discussion

References

  1. ↑ Mirtazapine 15mg Tablets - Summary of Product Characteristics (SmPC) - (emc) 
  2. ↑ "REMERON (mirtazapine) tablet, film coated [Organon Pharmaceuticals USA]". DailyMed. Organon Pharmaceuticals USA. October 2012. Retrieved 24 October 2013.
  3. ↑ Schatzberg, A. F., Cole, J. O., DeBattista, C. (2010). Manual of clinical psychopharmacology. 3 (7th ed ed.). American Psychiatric Pub. ISBN 9781585623778. 
  4. ↑ Gorman, J. M. (1999). "Mirtazapine: clinical overview". The Journal of Clinical Psychiatry. 60 Suppl 17: 9–13; discussion 46–48. ISSN 0160-6689. 
  5. ↑ "Review of the use of mirtazapine in the treatment of depression". Expert Opinion on Pharmacotherapy. 
  6. ↑ 6.0 6.1 6.2 Anttila, S. A. K., Leinonen, E. V. J. (7 June 2006). "A Review of the Pharmacological and Clinical Profile of Mirtazapine". CNS Drug Reviews. 7 (3): 249–264. doi:10.1111/j.1527-3458.2001.tb00198.x. ISSN 1080-563X. 
  7. ↑ 7.0 7.1 7.2 7.3 Croom, K. F., Perry, C. M., Plosker, G. L. (1 May 2009). "Mirtazapine". CNS Drugs. 23 (5): 427–452. doi:10.2165/00023210-200923050-00006. ISSN 1179-1934. 
  8. ↑ 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. (December 2005). "Mirtazapine Treatment of Social Phobia in Women: A Randomized, Double-Blind, Placebo-Controlled Study". Journal of Clinical Psychopharmacology. 25 (6): 580–583. doi:10.1097/01.jcp.0000186871.04984.8d. ISSN 0271-0749. 
  9. ↑ Mirtazapine Treatment of Obsessive-Compulsive Disorder | http://journals.lww.com/psychopharmacology/Citation/2001/10000/Mirtazapine_Treatment_of_Obsessive_Compulsive.16.aspx
  10. ↑ Carpenter, L., Leon, Z., Yasmin, S., Price, L. (1 June 1999). "Clinical Experience with Mirtazapine in the Treatment of Panic Disorder". Annals of Clinical Psychiatry. 11 (2): 81–86. doi:10.3109/10401239909147053. ISSN 1040-1237. 
  11. ↑ Landowski, J. (December 2002). "[Mirtazapine--an antidepressant]". Psychiatria Polska. 36 (6 Suppl): 125–130. ISSN 0033-2674. 
  12. ↑ Chinuck, R. S., Fortnum, H., Baldwin, D. R. (December 2007). "Appetite stimulants in cystic fibrosis: a systematic review". Journal of Human Nutrition and Dietetics. 20 (6): 526–537. doi:10.1111/j.1365-277X.2007.00824.x. ISSN 0952-3871. 
  13. ↑ "Management of symptons associated with advanced cancer: olanzapine and mirtazapine". Expert Review of Anticancer Therapy. 
  14. ↑ Hartmann, P. M. (1 January 1999). "Mirtazapine: a newer antidepressant". American Family Physician. 59 (1): 159–161. ISSN 0002-838X. 
  15. ↑ Jindal, R. D. (1 April 2009). "Insomnia in Patients with Depression". CNS Drugs. 23 (4): 309–329. doi:10.2165/00023210-200923040-00004. ISSN 1179-1934. 
  16. ↑ Nutt, D. J. (June 2002). "Tolerability and safety aspects of mirtazapine". Human Psychopharmacology: Clinical and Experimental. 17 (S1): S37–S41. doi:10.1002/hup.388. ISSN 0885-6222. 
  17. ↑ 17.0 17.1 Li, T.-C., Shiah, I.-S., Sun, C.-J., Tzang, R.-F., Huang, K.-C., Lee, W.-K. (June 2011). "Mirtazapine Relieves Post-Electroconvulsive Therapy Headaches and Nausea: A Case Series and Review of the Literature". The Journal of ECT. 27 (2): 165–167. doi:10.1097/YCT.0b013e3181e63346. ISSN 1095-0680. 
  18. ↑ Kast, R. E., Foley, K. F. (July 2007). "Cancer chemotherapy and cachexia: mirtazapine and olanzapine are 5-HT3 antagonists with good antinausea effects". European Journal of Cancer Care. 16 (4): 351–354. doi:10.1111/j.1365-2354.2006.00760.x. ISSN 0961-5423. 
  19. ↑ Twycross, R. (1 January 2003). "Itch: scratching more than the surface". QJM. 96 (1): 7–26. doi:10.1093/qjmed/hcg002. ISSN 1460-2393. 
  20. ↑ Greaves, M. W. (17 November 2005). "Itch in systemic disease: therapeutic options: Itch in systemic disease". Dermatologic Therapy. 18 (4): 323–327. doi:10.1111/j.1529-8019.2005.00036.x. ISSN 1396-0296. 
  21. ↑ Colombo, B., Annovazzi, P. O. L., Comi, G. (1 October 2004). "Therapy of primary headaches: the role of antidepressants". Neurological Sciences. 25 (3): s171–s175. doi:10.1007/s10072-004-0280-x. ISSN 1590-3478. 
  22. ↑ Tajti, J., Almási, J. (June 2006). "[Effects of mirtazapine in patients with chronic tension-type headache. Literature review]". Neuropsychopharmacologia Hungarica: A Magyar Pszichofarmakologiai Egyesulet Lapja = Official Journal of the Hungarian Association of Psychopharmacology. 8 (2): 67–72. ISSN 1419-8711. 
  23. ↑ NCI Thesaurus - Mirtazapine (Code C29265) 
  24. ↑ 24.0 24.1 24.2 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. (1 March 2005). "Discovery of New Tetracyclic Tetrahydrofuran Derivatives as Potential Broad-Spectrum Psychotropic Agents". Journal of Medicinal Chemistry. 48 (6): 1709–1712. doi:10.1021/jm049632c. ISSN 0022-2623. 
  25. ↑ Boer, Th. de, Maura, G., Raiteri, M., Vos, C. J. de, Wieringa, J., Pinder, R. M. (1 April 1988). "Neurochemical and autonomic pharmacological profiles of the 6-aza-analogue of mianserin, org 3770 and its enantiomers". Neuropharmacology. 27 (4): 399–408. doi:10.1016/0028-3908(88)90149-9. ISSN 0028-3908. 
  26. ↑ Boer, T. de (1996). "The pharmacologic profile of mirtazapine". The Journal of Clinical Psychiatry. 57 Suppl 4: 19–25. ISSN 0160-6689. 
  27. ↑ 27.0 27.1 Goodman, L. S., Brunton, L. L., Chabner, B., Knollmann, B. C., eds. (2011). Goodman & Gilman’s pharmacological basis of therapeutics (12th ed ed.). McGraw-Hill. ISBN 9780071624428. 
  28. ↑ 28.0 28.1 TGA eBS - Product and Consumer Medicine Information Licence 
  29. ↑ 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. (3 January 2000). "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". Bioorganic & Medicinal Chemistry Letters. 10 (1): 71–74. doi:10.1016/s0960-894x(99)00591-0. ISSN 0960-894X. 
  30. ↑ Wikström, H. V., Mensonides-Harsema, M. M., Cremers, T. I. F. H., Moltzen, E. K., Arnt, J. (1 July 2002). "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". Journal of Medicinal Chemistry. 45 (15): 3280–3285. doi:10.1021/jm010566d. ISSN 0022-2623. 
  31. ↑ Schreiber, S., Rigai, T., Katz, Y., Pick, C. G. (September 2002). "The antinociceptive effect of mirtazapine in mice is mediated through serotonergic, noradrenergic and opioid mechanisms". Brain Research Bulletin. 58 (6): 601–605. doi:10.1016/S0361-9230(02)00825-0. ISSN 0361-9230. 
  32. ↑ Dapoigny, M., Abitbol, J. L., Fraitag, B. (October 1995). "Efficacy of peripheral kappa agonist fedotozine versus placebo in treatment of irritable bowel syndrome. A multicenter dose-response study". Digestive Diseases and Sciences. 40 (10): 2244–2249. doi:10.1007/BF02209014. ISSN 0163-2116. 
  33. ↑ Pande, A. C., Pyke, R. E., Greiner, M., Wideman, G. L., Benjamin, R., Pierce, M. W. (October 1996). "Analgesic efficacy of enadoline versus placebo or morphine in postsurgical pain". Clinical Neuropharmacology. 19 (5): 451–456. doi:10.1097/00002826-199619050-00009. ISSN 0362-5664. 
  34. ↑ Rimoy, G. H., Wright, D. M., Bhaskar, N. K., Rubin, P. C. (1994). "The cardiovascular and central nervous system effects in the human of U-62066E. A selective opioid receptor agonist". European Journal of Clinical Pharmacology. 46 (3): 203–207. doi:10.1007/BF00192549. ISSN 0031-6970. 
  35. ↑ Al-Majed, A., Bakheit, A. H., Alharbi, R. M., Abdel Aziz, H. A. (2018). "Mirtazapine". Profiles of Drug Substances, Excipients, and Related Methodology. 43: 209–254. doi:10.1016/bs.podrm.2018.01.002. ISSN 1871-5125. 
  36. ↑ Schatzberg, A. F., Nemeroff, C. B., eds. (2009). The American Psychiatric Publishing textbook of psychopharmacology (4th ed ed.). American Psychiatric Pub. ISBN 9781585623099. 
  37. ↑ https://www.drugs.com/sfx/mirtazapine-side-effects.html
  38. ↑ Taylor, D., Paton, C., Kapur, S., eds. (2012). The Maudsley prescribing guidelines in psychiatry (11. ed ed.). Wiley. ISBN 9780470979488. 
  39. ↑ White N, Litovitz T, Clancy C (December 2008). "Suicidal antidepressant overdoses: a comparative analysis by antidepressant type" (PDF). Journal of Medical Toxicology. 4 (4): 238–50. doi:10.1007/bf03161207. PMC 3550116  . PMID 19031375. 
  40. ↑ Fawcett, J., Barkin, R. L. (1 December 1998). "Review of the results from clinical studies on the efficacy, safety and tolerability of mirtazapine for the treatment of patients with major depression". Journal of Affective Disorders. 51 (3): 267–285. doi:10.1016/S0165-0327(98)00224-9. ISSN 0165-0327. 
  41. ↑ Holzbach R, Jahn H, Pajonk FG, Mähne C (November 1998). "Suicide attempts with mirtazapine overdose without complications". Biological Psychiatry. 44 (9): 925–6. doi:10.1016/S0006-3223(98)00081-X. PMID 9807651. Template:Unreliable medical source
  42. ↑ Retz W, Maier S, Maris F, Rösler M (November 1998). "Non-fatal mirtazapine overdose". International Clinical Psychopharmacology. 13 (6): 277–9. doi:10.1097/00004850-199811000-00007. PMID 9861579. Template:Unreliable medical source
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  44. ↑ Baselt, RC (2008). Disposition of Toxic Drugs and Chemicals in Man (8th ed.). Foster City, CA: Biomedical Publications. pp. 1045–7. ISBN 978-0-9626523-7-0. 
  45. ↑ Buckley NA, McManus PR (December 2002). "Fatal toxicity of serotoninergic and other antidepressant drugs: analysis of United Kingdom mortality data". BMJ. 325 (7376): 1332–3. doi:10.1136/bmj.325.7376.1332. PMC 137809  . PMID 12468481. Template:Unreliable medical source
  46. ↑ MHRA (November 10, 2006). "MHRA license for Modafinil in UK" (PDF). MHRA. 
  47. ↑ "Medicines Act 1968 Section 13". 


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