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Mirtazapine (Remeron) is a psychoactive drug of the benzazepine and tetracyclic antidepressant (TeCA) chemical classes which is used primarily as an antidepressant. It is sometimes used for its anxiolytic, hypnotic, antiemetic, orexigenic, and antihistamine or antipruritic effects. Mirtazapine was introduced by Organon International in 1994. Along with its chemical analogue and predecessor mianserin (Bolvidon, Norval, Tolvon), mirtazapine is one of the few noradrenergic and specific serotonergic antidepressants (NaSSAs).


Mirtazapine's primary use is the treatment of moderate to severe clinical depression. Mirtazapine has been found to be useful in the treatment of generalized anxiety disorder (GAD), social anxiety disorder (SAD) or social phobia (SP), obsessive-compulsive disorder (OCD), panic disorder (PD), post-traumatic stress disorder (PTSD), seasonal affective disorder (SAD), insomnia, nausea and vomiting or emesis, loss of appetite or anorexia and subsequent unintentional weight loss,, and itch or pruritus as well, and it may be prescribed off-label for these condition.

Mirtazapine has also been found to be efficient in the treatment of shallow breathing and pauses in respiration during sleep or sleep apnea/hypopnea (SAHS), headaches such as migraine, tension headache or chronic tension-type headache (CTTH), post-dural puncture headache (PDPH) and cluster headache, severe morning sickness in pregnant women or hyperemesis gravidarum, irritable bowel syndrome (IBS), gastroparesis, distortion or decrease in the sense of taste or dysgeusia, undifferentiated somatoform disorder (USD), autism and other pervasive developmental disorders (PDDs), and antipsychotic or neuroleptic-induced akathisia.


A four step chemical synthesis of mirtazapine has been published.


Mirtazapine is a potent antagonist at the following receptor: H1 (~0.75 nM) > 5-HT2A (~10 nM) = 5-HT2C (~10 nM) = 5-HT3 (~10 nM) > α2-adrenergic (~100 nM). It also has weak but clinically negligible affinity as an antagonist for the following sites: 5-HT2B receptor (~350 nM) > α1-adrenergic receptor (~500 nM) > muscarinic acetylcholine receptors (mAChRs) (~1000 nM) > norepinephrine transporter (NET) (~1250 nM).

Antagonization of the α2-adrenergic receptors which function largely as pre-synaptic autoreceptors and heteroreceptors enhances adrenergic and serotonergic neurotransmission, notably central 5-HT1A receptor-mediated transmission. Because of this, mirtazapine has been said to be a functional "indirect agonist" of the 5-HT1A receptor. Increased activation of the central 5-HT1A receptor is thought to be the primary mediator of efficacy of most antidepressant drugs. Unlike most conventional antidepressants, however, mirtazapine is not a reuptake inhibitor and has no appreciable affinity for the serotonin, norepinephrine, or dopamine transporters, nor is it an MAOI or have any efficacy at inhibiting/inducing any other enzyme for that matter.

Despite its classification as a NaSSA based on its relatively weak actions at the α2-adrenergic receptor, mirtazapine's antidepressant properties are actually more likely to be mediated primarily by its far stronger blockade of various serotonin receptors, notably the 5-HT2C receptor. This is probably why yohimbine (found in Pausinystalia yohimbe ("Yohimbe")) which is a similar-acting and even more potent α2-adrenergic receptor antagonist that lacks 5-HT2C receptor affinity has far lower antidepressant efficacy in comparison. The 5-HT2C receptor normally works to inhibit the release of the neurotransmitter dopamine in various parts of the brain, notably in the pleasure centers such as the ventral tegmental area (VTA). By blocking it, mirtazapine disinhibits dopamine activity in these areas, causing a pronounced antidepressant and anxiolytic response. Indeed, the novel antidepressant agomelatine (Valdoxan) acts primarily as a 5-HT2C receptor antagonist and has antidepressant efficacy at least comparable to that of the SSRIs and SNRIs.

Antagonism of the 5-HT2A and 5-HT2C receptors has beneficial effects on anxiety, sleep and appetite, as well as sexual function regarding the latter. Additionally, antagonism of the 5-HT3 receptor, the mechanism of action of the highly effective and popular antiemetic ondansetron (Zofran), significantly improves pre-existing symptoms of nausea, vomiting, diarrhea, and general irritable bowel syndrome in afflicted individuals. Mirtazapine may be used as an inexpensive and possibly even superior antiemetic alternative to ondansetron. Blockade of the 5-HT3 receptors has also shown to improve anxiety and drug addiction in several studies. Mirtazapine appears to be nootropic via enhancing memory functioning as well. In contrast to mirtazapine, the SSRIs, SNRIs, TCAs, and MAOIs all increase the general activity of the 5-HT2A, 5-HT2C, and 5-HT3 receptors, leading to a host of negative changes and side effects, the most prominent of which include anorexia, insomnia, sexual dysfunction (impaired libido and anorgasmia), nausea, and diarrhea, among others. As a result, mirtazapine is often used in conjunction with these drugs to reduce their side effect profile and to produce a stronger antidepressant effect.

Mirtazapine is the strongest H1 receptor antagonist known to exist on the market and as a result, it can cause powerful sedative and hypnotic effects. After a short period of chronic treatment, however, the H1 receptor tends to sensitize and the antihistamine effects become more tolerable. Many patients may also dose at night to avoid the effects and this appears to be an effective strategy for combating them. Blockade of the H1 receptor may improve pre-existing allergies, pruritus, nausea, and insomnia in afflicted individuals; hence, this may actually be a positive thing for some. It may also contribute to weight gain, however. Mirtazapine has very low affinity for the muscarinic acetylcholine receptors and therefore lacks any significant anticholinergic properties.

Mirtazapine's close chemical analogue mianserin (Bolvidon, Norval, Tolvon) has been demonstrated to be a potent 5-HT6 and 5-HT7 receptor antagonist. Mirtazapine is not known to have ever been screened for binding affinity at these receptors, and may very well act on them as well. If mirtazapine does indeed bind to and act as an antagonist at these receptors, the effects induced by this action may contribute considerably to its antidepressant, anxiolytic, sleep-enhancing, and potential nootropic properties, as well as its utility in combating the side effect of pro-serotonergic antidepressants such as the SSRIs.


Mirtazapine 30 mg tablets.

Mirtazapine is typically prescribed in doses ranging from 15 mg to 45 mg. However, in severely depressed individuals, doses as high as 120 mg have been used with success. Mirtazapine has a half-life of approximately 20–40 hours. Like most other antidepressants, because of the "therapeutic lag" mirtazapine may require as long as 2–4 weeks until the therapeutic benefits of the drug become manifest. Mirtazapine can be sedating at lower doses in the 15–30 mg range mainly because of its antihistamine action, but at higher doses in the 45–90 mg range the enhanced adrenergic activity partially counteracts these effects and it becomes more stimulating. If patients find mirtazapine to be too sedating, it is recommended that they contact their doctor and perhaps request a higher dose. If the patient is sensitive to medication constant monitoring should be taken.

Efficacy and tolerability

Mirtazapine has been found to be one of the most effective antidepressants available and has a generally tolerable side effect profile. In a major systematic review published in 2009 which compared the efficacy and tolerability of 12 popular antidepressants, mirtazapine, escitalopram (Lexapro, Cipralex), venlafaxine (Effexor), and sertraline (Zoloft, Lustral) were shown to be superior to all of the included SSRIs, all of the SNRIs, the norepinephrine reuptake inhibitor reboxetine (Edronax, Vestra), (NDRI) bupropion (Wellbutrin, Zyban), and the noradrenergic and specific serotonergic antidepressant (NaSSA) mianserin (Bolvidon, Norval, Tolvon) in terms of antidepressant efficacy, while mirtazapine was average in regards to tolerability. Mirtazapine has been demonstrated to be superior to trazodone (Desyrel) as well. Mirtazapine has also been shown to be equal in efficacy to many of the TCAs, including amitriptyline (Elavil), doxepin (Sinequan, Adapin), and clomipramine (Anafranil), but with a much improved tolerability profile. However, two other studies found mirtazapine inferior to the TCA imipramine (Tofranil). One study compared the combination of venlafaxine (Effexor) and mirtazapine versus the MAOI tranylcypromine (Parnate) and found them to be equally effective, though the MAOI was much less tolerable in terms of side effect and drug interactions.

Side effects

Common side effect of mirtazapine include dizziness, blurred vision, sedation, drowsiness or somnolence, malaise or lassitude, increased appetite or hyperphagia and subsequent weight gain,, agitation or restlessness, irritability or aggression, apathy or anhedonia or emotional blunting, excessive mellowness or calmness, dry mouth or xerostomia, difficulty swallowing or dysphagia, shallow breathing or hypoventilation or respiratory depression, constipation, decreased body temperature or hypothermia, pupil constriction or miosis, enhanced libido and sexual function or aphrodisia, wet dreams or nocturnal emission, spontaneous orgasm, loss of balance, vertigo, and restless legs syndrome (RLS). Mirtazapine has also occasionally been reported to cause mild psychedelic effects in some patients, including mental imagery, auditory and visual hallucinations, and particularly, vivid, bizarre, and even lucid dreams or nightmares. Most of these side effects are generally mild and become less prominent over time.

Rare and potentially serious adverse reaction may include allergic reaction, abnormal fluid accumulation or edema, fainting or syncope, seizures or convulsions, bone marrow suppression or myelotoxicity, ineffective myeloid blood cell production or myelodysplasia, and white blood cell reduction or agranulocytosis (occurs in 1/1,000 patients).

Mirtazapine seems to have lower risk of many of the side effects encountered with related antidepressants, such as decreased appetite or anorexia, insomnia, nausea and vomiting or emesis, diarrhea, urinary retention or ischuria, increased body temperature or hyperthermia, increased perspiration or sweating, pupil dilation or mydriasis, or sexual dysfunction (consisting of loss of libido and anorgasmia).

In general, antidepressants may have the capacity to exacerbate some patients' depression or anxiety or cause suicidal ideation, particularly when first starting treatment, although this is rare. , there was no evidence that mirtazapine differs from other antidepressants in this regard, but studies of such rare effects need to follow a larger number of participants over a longer time to give a clearer picture either way.


Mirtazapine and other antidepressants generally produce a degree of physical dependence and may cause a withdrawal upon discontinuation, though such effects are usually much less severe with mirtazapine in comparison to the SSRIs and related drugs. It should be noted that the withdrawal effects of antidepressants are typically nowhere near as strong as those of the benzodiazepines. A gradual and slow reduction in dose is recommended in order to minimize withdrawal symptoms. Effects of sudden cessation of treatment with mirtazapine may include depression, anxiety, panic attacks, vertigo, restlessness, irritability, decreased appetite or anorexia, insomnia, diarrhea, nausea and vomiting, flu-like symptoms such as allergies or pruritus, headache or migraine, and sometimes hypomania or mania.


The potential for dangerous drug interactions with mirtazapine is considered to be very low, if not completely negligible. As a serotonin receptor antagonist, mirtazapine will not cause serotonin syndrome at any dose, nor is it capable of causing tyramine-induced hypertensive crisis, unlike the SSRIs and MAOIs, respectively. In fact, mirtazapine can actually be used to treat serotonin syndrome. The only notable interactions are that mirtazapine may increase the sedative effects of certain drugs such as alcohol and the benzodiazepines, and it has also been reported to reduce or block the effects of some street drugs, including entactogens like MDMA (ecstasy) and psychedelic such as LSD (acid) and psilocybe mushroom (magic mushrooms).

Mirtazapine in combination with an SSRI, SNRI, or TCA as an augmentation strategy is perfectly safe and is often used therapeutically. Mirtazapine and MAOIs are said to be contraindicated by some sources; however, there is no true indication that this is actually the case, and there is no proper literature on the subject warning against the combination whatsoever. Only a single study has mentioned anything significantly important regarding the combination, and they reported that it does not result in any incidence of serotonin-related toxicity. However, mirtazapine has been associated with inducing hypertension in clonidine-treated patients, and due to MAOIs' similar action to clonidine via octopamine, this combination may be expected to disinhibit adrenergic effects of MAOIs (possibly to the point of hypertension).


Mirtazapine is relatively safe if an overdose is taken. Unlike the TCAs, mirtazapine shows no significant cardiovascular adverse effect at 7 to 22 times the maximum recommended dose. Overdose with as much as 30 to 50 times the standard dose has shown to be relatively non-toxic. One case in which 1,200 mg was ingested proved non-fatal, but this is merely anecdotal. There are no reports of anyone dying as a consequence of mirtazapine use, combination, or overdose.

Trade names

Mirtazapine is marketed under many different brand names in various parts of the world, including:

  • In Chilemarker: Amirel, Divaril, Promyrtil and Zuleptan.
  • In Finlandmarker: Alphamirt, Alphazagen, Finmirtaza, Finpharma, Finscope, Genamirt, Hexazipin, Loxozapin, Medizapin, Mirtacur, Mirtamerck, Mirtapharm, Mirtalphagen, Mirtamed, Mirtapin, Mirtaratio, Mirtaril, Mirtascope, Mirtasole, Mirtastada, Mirtatifi, Mirtatsapiini, Mirtazon, Mirtoral, Mirzaten, Pharmasole, Pharmazepine, Tarzapine, Tazascope and Tirzamed.
  • In Germanymarker: Loxozapin, Mirta, Mirtagamma, Mirtapin, Mirtazepin, Mirtazelon and Mirtazza.
  • In the Republic of Irelandmarker: Bexzis, Mirap, Tazamel, Zismirt and Zistap.

Mirtazapine was known as 6-Azamianserin and ORG-3770 while in early clinical development.

See also

General classification
Effects classification
Pharmacological classification
Similar or related compounds


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