Mirtazapine
527555
226079501
2008-07-16T19:04:42Z
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Reverting possible vandalism by [[Special:Contributions/77.102.53.233|77.102.53.233]] to version by Nsaa. False positive? [[User:ClueBot/FalsePositives|Report it]]. Thanks, [[User:ClueBot]]. (441730) (Bot)
{{Drugbox|
|IUPAC_name = 2-methyl-1,2,3,4,10,14b- hexahydrobenzo[''c'']pyrazino[1,2-''a''] pyrido[3,2-''f'']azepine
| image=Mirtazapine2.png
| width=160
| CAS_number=61337-67-5
| ATC_prefix=N06
| ATC_suffix=AX11
| ATC_supplemental=
| PubChem=4205
| DrugBank=
| C=17 | H=19 | N=3
| molecular_weight = 265.36
| bioavailability= 50%
| metabolism = [[Liver]]
| elimination_half-life=37 hours (females), 26 hours (males)
| excretion = 75% urine 15% feces
| pregnancy_category = C
| legal_status = Prescription only
| routes_of_administration= Oral tablet, Soluble tablet
}}
'''Mirtazapine''' is an [[antidepressant]] introduced by [[Organon International]] in [[1994]] used for the treatment of moderate to severe [[clinical depression|depression]]. Mirtazapine has a [[Tetracyclic compound|tetracyclic]] [[chemical structure]] and is classified as a [[noradrenergic and specific serotonergic antidepressant]] ([[NaSSA]]). Mirtazapine and [[Maprotiline]] are the only tetracyclic antidepressants that have been approved by the U.S. [[Food and Drug Administration]] to treat depression. Because of its unique pharmacologic profile, mirtazapine is virtually devoid of [[anticholinergic]] effects, [[serotonin syndrome|serotonin-related side effects]],{{ref|Burrows}} and adrenergic side effects ([[orthostatic hypotension]] and [[sexual dysfunction]]). Antihistaminic side effects of drowsiness and weight gain are prominent. It is most useful as an add-on medication to enhance the effectiveness of agents such as [[duloxetine]] and [[venlafaxine]] in severe and treatment-resistant depression. Mirtazapine is relatively safe if an overdose is taken.{{ref|Velazquez}}
==Trade names==
'''Mirtazapine''' is marketed under the tradenames:
* '''Remeron''' in [[Brazil]], [[Canada]], [[Czech Republic]], [[Denmark]], [[Estonia]], [[Finland]], [[Greece]], [[Israel]], [[Italy]], [[Mexico]], [[Netherlands]], [[Norway]], [[Pakistan]], [[Sweden]], [[Switzerland]], [[Turkey]],[[Malaysia]] and the [[United States]]
* '''Zispin''' in [[Ireland]] and the [[United Kingdom]]
* '''Remergil''' in [[Germany]]
* '''Norset''' in [[France]]
* '''Rexer''' in [[Spain]]
* '''Remergon''' in [[Belgium]]
* '''Mirtabene''' in [[Austria]]
* '''Avanza''', '''Mirtazon''' and '''Axit''' in [[Australia]]
* '''Mirtaz''' in [[India]] and [[Srilanka]]
* '''Promyrtil''' in [[Chile]]
* '''Noxibel''' in [[Bolivia]]
* '''Remeron''', '''Mirzaten''' and '''Mizapin Sol''' in [[Hungary]]
==Indications==
===Approved use===
Mirtazapine is primarily used to treat the symptoms of moderate to severe [[clinical depression|depression]].{{ref|Gorman}}
===Unapproved and off-label use===
There is evidence that mirtazapine can be used to treat [[panic disorder]] (PD),{{ref|Baldwin}} [[generalized anxiety disorder]] (GAD),{{ref|Goodnick}} [[obsessive-compulsive disorder]] (OCD),{{ref|Koran}} [[post traumatic stress disorder]] (PTSD){{ref|Baldwin}} [[sleep apnea]],{{ref|ScienceDaily}} and [[pruritus]].{{ref|Davis}} Mirtazapine has been reported to be effective in the [[prophylactic]] treatment of [[chronic]] [[tension headache]].{{ref|Bendtsen}} This drug has also been shown to improve symptoms in [[Gastroparesis]] patients.
===Veterinary use===
Anecdotal evidence also suggests that mirtazapine may be effective in treating certain vomiting or anorexia-related conditions in dogs and cats. Any such use is still off-label, however.{{ref|Brooks}}
==Mechanism of action==
It is thought to work by blocking presynaptic [[Alpha-2 adrenergic receptor]]s that normally inhibit the release of the
[[neurotransmitter]]s [[norepinephrine]] ([[noradrenaline]]) and [[serotonin]], thereby increasing active levels in the [[synapse]]. Mirtazapine is a potent antagonist of 5-HT2 and 5-HT3 receptors. Mirtazapine has no significant affinity
for the 5-HT1A and 5-HT1B receptors.
==Side effects==
Interestingly, its side-effect profile can be used for benefit in certain clinical situations. The drowsiness, increased appetite, and weight gain that it causes are useful in patients with depressive disorders with prominent sleep and appetite disturbances. In addition, it is quite useful in patient situations in which patients suffer from nausea, since it also antagonizes the 5-HT<sub>3</sub> receptor, the target of the popular anti-emetic [[ondansetron]] ([[Zofran]]).
At lower doses, mirtazapine is primarily [[antihistamine]]rgic, causing sedation, which can be beneficial in depressed patients who have difficulty falling asleep. Higher doses are generally less sedating as its antihistaminergic properties are thought to be offset by increased noradrenaline release.{{ref|Nash}}
===Side effects occurring commonly:===
* Mild visual [[hallucinations]] (when taken during the day or when awake)
* Increased [[appetite]]
* Vivid dreams / [[Nightmares]] as a result of regular intake
* [[Depersonalization]] / [[Derealization]] (i.e. feeling unreal, in a dream-like state)
* Weight gain
* Increase in cholesterol, independent of weight gain
*[[Drowsiness]], especially at lower doses and during the first few weeks of treatment
*[[Dizziness]], coupled often with the effects of [[sickness]]
*[[Headache]]
*General or local swelling
===Side effects occurring rarely:===
*Excessive urinating when taken with [[alcohol]]
*[[Mania]]
*[[Seizures]]
*[[Tremor]]
*Muscle twitching and [[Restless Legs Syndrome]]
*[[Pins and needles]]
*[[Rash]] and skin eruptions
*Pain in the joints or muscles
*Low blood pressure
*Higher blood pressure
*Obesity
===Dangerous side effects===
Any of these side effects requires urgent medical attention. Medical advice is also required for taper-off instructions: sudden withdrawal from antidepressants can cause serious symptoms. However, sudden withdrawal can be used, under appropriate medical supervision, when the risks of continuing the antidepressant during a 'taper-off' phase are too great.
*An allergic reaction; signs of swelling of the lips, face and tongue, difficulty in breathing, rash or itching (especially affecting the whole body) or feeling faint
*Signs of infection such as fever, sore throat, mouth ulcers or stomach upset
*[[Jaundice]] (yellowing of the skin and/or eyes)
*[[Agranulocytosis]]
===Withdrawal symptoms===
In comparison with some other antidepressants, mirtazapine [[discontinuation syndrome]] is relatively mild.{{fact|date=July 2008}} Effects of sudden cessation of treatment may include:
*Nausea
*[[Vertigo (medical)|Vertigo]]/[[dizziness]]
*[[Headache]]
*[[Anxiety]]
As with most antidepressants, a gradual and slow reduction in dose is recommended in order to minimize DS effects.
==Dosage==
[[Image:Mirtazapine_30mg.jpg|thumb|right|120px|Mirtazapine 30 mg tablets]]
The usual starting dose for mirtazapine is 15 mg once daily, usually at bedtime (because of its sedative nature and the possibility of disturbed visual perception). Doses may be increased, following medical advice, every 1-2 weeks up to a dose of 45 mg. It may be taken with or without food. Dispersible tablets (SolTab orally disintegrating tablets) can be taken without water.
==Pregnancy and lactation==
*Pregnancy : Sufficient data in humans is lacking. The use should be justified by the severity of the condition to be treated.
*Lactation : Sufficient data in humans is also lacking. Additionally, Mirtazapine may be found in the maternal milk in significant concentrations. The use in breastfeeding women should be carefully weighed against possible risks.
== Interactions with other drugs==
Because of the sedative effects of Mirtazapine, excessive sedation may result when it is used with other sedating substances, such as alcohol or [[benzodiazepines]].
According to official prescribing information from Organon, Mirtazapine should not be used within 14 days of the use of an [[monoamine oxidase inhibitor|MAOI]] because of the risk of serious effects such as [[hypertensive emergency]] and [[hyperthermia]].
==References==
{{refbegin}}
#{{note|Gillman}} {{cite journal | author=Gillman, PK | title=A systematic review of the serotonergic effects of mirtazapine: implications for its dual action status | journal=Human Psychopharmacology Clinical and Experimental | volume=21 | issue=2 | year=2006 | pages=117–25| pmid=16342227 | doi=10.1002/hup.750 }}
#{{note|Burrows}} {{cite journal | author=Burrows GD, Kremer CM. | title=Mirtazapine: clinical advantages in the treatment of depression | journal=Journal of Clinical Psychopharmacology | volume=17 | issue=2S | year=1997 | pages=34S–39S| pmid=9090576 | doi=10.1097/00004714-199704001-00005 }}
#{{note|Velazquez}} {{cite journal | author=Velazquez C, Carlson A, Stokes KA, Leikin JB.
| title=Relative safety of mirtazapine overdose | journal= Veterinary and Human Toxicology | volume=43 | issue=6 | year=2001 | pages=342–344| pmid=11757992 }}
#{{note|Gorman}} {{cite journal | author=Gorman JM | title=Mirtazapine: clinical overview | journal=Journal of Clinical Psychiatry | volume=60 | issue=17 | year=1999 | pages=9–13| pmid=10446735 }}
#{{note|Baldwin}} {{cite journal | author=Baldwin DS, Anderson IM, Nutt DJ, Bandelow B, Bond A, Davidson JR, den Boer JA, Fineberg NA, Knapp M, Scott J, Wittchen HU | title=Evidence-based guidelines for the pharmacological treatment of anxiety disorders: recommendations from the British Association for Psychopharmacology | journal=Journal of Psychopharmacology | volume=19 | issue=6 | year=2005 | pages=567–596| pmid=16272179 | doi=10.1177/0269881105059253 }}
#{{note|Goodnick}} {{cite journal | author=Goodnick PJ, Puig A, DeVane CL, Freund BV | title=Mirtazapine in major depression with comorbid generalized anxiety disorder | journal=Journal of Clinical Psychiatry | volume=60 | issue=7 | year=1999 | pages=446–448| pmid=10453798 }}
#{{note|Koran}} {{cite journal | author=Koran LM, Gamel NN, Choung HW, Smith EH, Aboujaoude EN | title=Mirtazapine for obsessive-compulsive disorder: an open trial followed by double-blind discontinuation | journal=Journal of Clinical Psychiatry | volume=66 | issue=4 | year=2005 | pages=515–520| pmid=15816795 }}
#{{note|ScienceDaily}}{{cite web | title = First Effective Drug For Sleep Disorder Identified | publisher = [[Science Daily]] | date = 2003-06-05 | url = http://www.sciencedaily.com/releases/2003/06/030605081837.htm | accessdate = 2008-05-01 }}
#{{note|Baldwin}} {{cite journal | author=Baldwin DS, Anderson IM, Nutt DJ, Bandelow B, Bond A, Davidson JR, den Boer JA, Fineberg NA, Knapp M, Scott J, Wittchen HU | title=Evidence-based guidelines for the pharmacological treatment of anxiety disorders: recommendations from the British Association for Psychopharmacology | journal=Journal of Psychopharmacology | volume=19 | issue=6 | year=2005 | pages=567–596| pmid=16272179 | doi=10.1177/0269881105059253 }}
#{{note|Davis}} {{cite journal | author=Davis MP, Frandsen JL, Walsh D, Andresen S, Taylor S. | title=Mirtazapine for pruritus | journal=Journal of pain and symptom management | volume=25 | issue=3 | year=2003 | pages=288–291| pmid=12614964 | doi=10.1016/S0885-3924(02)00645-0 }}
#{{note|Bendtsen}} {{cite journal | author=Bendtsen L, Jensen R | title=Mirtazapine is effective in the prophylactic treatment of chronic tension-type headache | journal=Neurology | volume=62 | issue=10 | year=2004 | pages=1706–1711| pmid=15159466 }}
#{{note|Brooks}} {{cite web | last = Brooks DVM, DipABVP | first = Wendy C. | title = Mirtazapine (Remeron) | work = The Pet Pharmacy | date = 2007-04-30 | url = http://www.veterinarypartner.com/Content.plx?P=A&A=2552 | accessdate = 2008-03-06 }}
#{{note|Nash}} {{cite journal | author=Nash J, Nutt D | title=Antidepressants | journal=Psychiatry | volume=6 | issue=7 | year=2004 | pages=289–294 }}
{{refend}}
==External links==
*[http://emc.medicines.org.uk/emc/assets/c/html/displaydoc.asp?documentid=17876 Patient Information Leaflet (pdf)]
*[http://www.remeronsoltab.com/Consumer/index.asp Official site of Remeron]
{{Antidepressants}}
[[Category:Tetracyclic antidepressants]]
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