Mirtazapine — BrandWiki

Mirtazapine

verifiedfields	verified
watchedfields	verified
verifiedrevid	408610027
width	250px
image2	Mirtazapine enantiomers ball-and-stick models from xtal 2011.png
width2	250px
tradename	Remeron, others
medlineplus	a697009
dailymedid	Mirtazapine
pregnancy au	B3
pregnancy au comment	‡R1R‡
routes of administration	By mouth, topical
class	Noradrenergic and specific serotonergic antidepressant (NaSSA)
atc prefix	N06
atc suffix	AX11
legal au	S4
legal br	C1
legal br comment	‡R2R‡
legal ca	Rx-only
legal uk	POM
legal us	Rx-only
legal us comment	‡R3R‡‡R4R‡
legal eu	Rx-only
bioavailability	50%‡R3R‡
protein bound	85%‡R3R‡
metabolism	Liver (CYP1A2, CYP2D6, CYP3A4)‡R3R‡
metabolites	Desmethylmirtazapine (contributes 3–10% of activity)‡R5R‡
elimination half-life	20–40 hours‡R5R‡‡R3R‡
excretion	Urine: 75%‡R5R‡ Feces: 15%‡R5R‡‡R3R‡
iuphar ligand	7241
cas number	85650-52-8
pubchem	4205
drugbank	DB00370
chemspiderid	4060
unii	A051Q2099Q
kegg	D00563
chebi	6950
chembl	654
synonyms	Mepirzapine; 6-Azamianserin; ORG-3770
iupac name	(±)-5-methyl-2,5,19-triazatetracyclo[13.4.0.02,7.08,13]nonadeca-1(15),8,10,12,16,18-hexaene
c	17
h	19
n	3
smiles	n1cccc3c1N4C(c2ccccc2C3)CN(C)CC4
stdinchi	1S/C17H19N3/c1-19-9-10-20-16(12-19)15-7-3-2-5-13(15)11-14-6-4-8-18-17(14)20/h2-8,16H,9-12H2,1H3
stdinchikey	RONZAEMNMFQXRA-UHFFFAOYSA-N
chirality	Racemic mixture
density	1.22
melting point	114
melting high	116
boiling point	432
solubility	Soluble in methanol and chloroform

Mirtazapine, sold under the brand name Remeron among others, is an atypical tetracyclic antidepressant, and as such is used primarily to treat depression.[6] Its effects may take up to four weeks but can also manifest as early as one to two weeks.[6] It is often used in cases of depression complicated by anxiety or insomnia.[7] The effectiveness of mirtazapine is comparable to other commonly prescribed antidepressants.[8] It is taken by mouth.[6]

Common side effects include sleepiness, dizziness, increased appetite, and weight gain.[6]

Medical uses

Mirtazapine is approved by the United States Food and Drug Administration for the treatment of major depressive disorder in adults.[14]

Depression

Mirtazapine is primarily used for major depressive disorder and other mood disorders.[15][16] Onset of action appears faster than some selective serotonin reuptake inhibitors and similar to tricyclic antidepressants.

In 2010, the National Institute for Health and Care Excellence recommended generic selective serotonin reuptake inhibitors as first-line choices, as they are "equally effective as other antidepressants and have a favourable risk–benefit ratio."[17] For mirtazapine, it found "no difference between mirtazapine and other antidepressants on any efficacy measure, although in terms of achieving remission mirtazapine appears to have a statistical though not clinical advantage. In addition, mirtazapine has a statistical advantage over selective serotonin reuptake inhibitors in terms of reducing symptoms of depression, but the difference is not clinically significant. However, there is strong evidence that patients taking mirtazapine are less likely to leave treatment early because of side effects, although this is not the case for patients reporting side effects or leaving treatment early for any reason."[18]

A 2011 Cochrane review comparing mirtazapine to other antidepressants found that while it appeared to have a faster onset in people for whom it worked (measured at two weeks), its efficacy was about the same as other antidepressants after six weeks' use.[19]

A 2012 review focused on antidepressants and sleep found that mirtazapine reduced the time it took to fall asleep and improved the quality of sleep in many people with sleep disorders caused by depression, but that it could also disturb sleep in many people, especially at higher doses, causing restless leg syndrome in 8 to 28% of people and in rare cases causes REM sleep behavior disorder.[20] This seemingly paradoxical dose–response curve of mirtazapine with respect to somnolence is owed to the exceptionally high affinity of the drug for the histamine H1, 5-HT2A, and 5-HT2C receptors; exhibiting near exclusive occupation of these receptors at doses ≤15 mg. However, at higher doses, inverse agonism and constitutive activation of the α2A-, α2B-, and α2C-adrenergic receptors begins to offset activity at H1 receptors leading to decreased somnolence and even a subjective sensation of "activation" in treated patients.[21]

A 2018 analysis of 21 antidepressants found them to be fairly similar overall. It found tentative evidence for mirtazapine being in the more effective group and middle in tolerability.[22]

After one week of usage, mirtazapine was found to have an earlier onset of action compared to selective serotonin reuptake inhibitors.[23][24]

Other

There is also some evidence supporting its use in treating the following conditions, for which it is sometimes prescribed off-label:

Generalized anxiety disorder[10][25][26]
Social anxiety disorder[27]
Obsessive–compulsive disorder[27]
Panic disorder[27]

Adverse effects

A 2011 Cochrane review found that, compared with other antidepressants, it is more likely to cause weight gain and sleepiness, but it is less likely to cause tremors than tricyclic antidepressants, and less likely to cause nausea and sexual dysfunction than selective serotonin reuptake inhibitors.[19]

Very common (≥10% incidence) adverse effects include constipation, dry mouth, sleepiness, increased appetite (17%) and weight gain (>7% increase in <50% of children).[3][39][40][41][42][43][44][45][46]

Common (1–10% incidence) adverse effects include weakness, confusion, dizziness, fasciculations (muscle twitches), peripheral edema (swelling, usually of the lower limbs), and abnormal lab results like elevated transaminases, elevated serum triglycerides, and elevated total cholesterol.[40]

Mirtazapine is not considered to have a risk of many of the side effects often associated with other antidepressants like the selective serotonin reuptake inhibitors and may improve certain ones when taken in conjunction with them.[10] (Those adverse effects include decreased appetite, weight loss, insomnia, nausea and vomiting, diarrhea, urinary retention, increased body temperature, excessive sweating, pupil dilation and sexual dysfunction.[10])

In general, some antidepressants, especially selective serotonin reuptake inhibitors, can paradoxically exacerbate some peoples' depression or anxiety or cause suicidal ideation.[47] Despite its sedating action, mirtazapine is also believed to be capable of this, so in the United States and certain other countries, it carries a black box label warning of these potential effects, especially for people under the age of 25.[6]

Mirtazapine may induce arthralgia (non-inflammatory joint pain).[48]

A case report published in 2000 noted an instance in which mirtazapine counteracted the action of clonidine, causing a dangerous rise in blood pressure.[49]

In a study comparing 32 antidepressants of all pharmacological classes, mirtazapine was one of the antidepressants most likely to cause nightmare disorder, sleepwalking, restless legs syndrome, night terrors and sleep paralysis.[50]

Mirtazapine has been associated with an increased risk of death compared to other antidepressants in several studies. However, it is more likely that the residual differences between people prescribed mirtazapine rather than a selective serotonin reuptake inhibitor account for the difference in risk of mortality.[51]

Withdrawal

Stopping Mirtazapine and other antidepressants may cause withdrawal symptoms.[10][52] A gradual and slow reduction in dose is recommended to minimize such symptoms.[53] Effects of sudden cessation of treatment with mirtazapine may include depression, anxiety, tinnitus, panic attacks, vertigo, restlessness, irritability, decreased appetite, insomnia, diarrhea, nausea, vomiting, flu-like symptoms, allergy-like symptoms such as pruritus, headaches, and sometimes mania or hypomania.[54][55]