Mirtazapine

What is/are Mirtazapine

Mirtazapine (Remeron, Avanza, Zispin) is a noradrenergic and specific serotonergic antidepressant (NaSSA) which was introduced by Organon International in the United States in 1990 and is used primarily in the treatment of depression. It is also commonly used as an anxiolytic, hypnotic, antiemetic, and appetite stimulant. Structurally, mirtazapine can also be classified as a tetracyclic antidepressant (TeCA). It is broadly classified as a centrally acting α2-adrenergic receptor antagonist.

Medical uses

Approved and off-label

Mirtazapine's primary use is the treatment of major depressive disorder and other mood disorders.

However, it has also been found useful in alleviating the following conditions and may be prescribed off-label for their treatment:

•     Generalized anxiety disorder
•     Social anxiety disorder
•     Obsessive-compulsive disorder
•     Panic disorder
•     Post-traumatic stress disorder
•     Low appetite/underweight
•     Insomnia
•     Nausea/vomiting
•     Itching
•     Headaches and migraine

Investigational

Mirtazapine has had literature published on its efficacy in the experimental treatment of the following conditions:

•     Sleep apnea/hypopnea
•     Inappropriate sexual behavior and other secondary symptoms of autistic spectrum conditions and other pervasive developmental disorders
•     Antipsychotic-induced akathisia
•     Drug withdrawal, dependence, and detoxification

Feline

Mirtazapine is sometimes prescribed as an appetite stimulant for cats experiencing anorexia due to medical conditions such as chronic kidney disease. It is especially useful for treating combined poor appetite and nausea in cats.
Efficacy and tolerability

In clinical studies, mirtazapine has been found to be an effective antidepressant with a generally tolerable side effect profile relative to other antidepressants.

In a major systematic review published in 2009 which compared the efficacy and tolerability of 12 popular antidepressants, mirtazapine was found to be superior to all of the included selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), and reboxetine, bupropion, and mianserin in terms of antidepressant efficacy, while it was average in regard to tolerability.[38] However, it is important to note that the efficacies of most of the antidepressants in this review differed only slightly. Hence, the apparent superiority of mirtazapine relative to most of the others included may not actually be all that prominent or significant in this case.[citation needed]

Compared to earlier antidepressants, mirtazapine has been found to be significantly superior to trazodone, while it has been shown to be approximately equivalent in efficacy to several of the tricyclic antidepressants (TCAs) including amitriptyline, doxepin, and clomipramine, though with a much improved tolerability profile.[2][40] However, two other studies found mirtazapine to be significantly inferior to imipramine, another TCA. One study compared the combination of venlafaxine and mirtazapine to the monoamine oxidase inhibitor (MAOI) tranylcypromine alone and found them to be similarly effective, though tranylcypromine was much less tolerable in regards to side effects and drug interactions.

All antidepressants, including mirtazapine, generally require a few weeks for their therapeutic benefits on depressive and anxious symptoms to become apparent. Unlike most antidepressants, however, mirtazapine has demonstrated itself to have a faster onset of antidepressant action with an initial reduction in affective symptoms being seen within the first week of treatment and the maximal change in improvement occurring over the course of the first two weeks. Hence, it may be a better choice for patients in whom hastened relief is urgently needed, such as those who are considered to be a suicide risk.

Adverse effects

Common side effects of mirtazapine include dizziness, blurred vision, sedation, somnolence, malaise, increased appetite, weight gain (as a result of increased appetite), dry mouth, constipation, and joint and muscle pain. Less common side effects that tend to occur more often at higher doses include restlessness, irritability, aggression, apathy, anhedonia, difficulty swallowing, shallow breathing, decreased body temperature, pupil constriction, nocturnal emissions, spontaneous orgasms, impaired balance, restless legs syndrome, and vivid dreams. Rare and potentially serious adverse reactions of mirtazapine include allergic reaction, edema, fainting, seizures, bone marrow suppression, myelodysplasia, and agranulocytosis.

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

In general, some antidepressants, especially SSRIs, can paradoxically exacerbate some patients' depression or anxiety or cause suicidal ideation.[49] Despite its sedating action, mirtazapine is also believed to be capable of this, and for this reason in the United States and certain other countries it carries a black box label warning of these potential effects.

Discontinuation

Mirtazapine and other antidepressants may cause a withdrawal syndrome upon discontinuation. 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, insomnia, diarrhea, nausea, vomiting, flu-like symptoms such as allergies and pruritus, headaches, and sometimes hypomania or mania.

Overdose

Mirtazapine is considered to be relatively safe in the event of an overdose. Unlike the TCAs, mirtazapine showed no significant cardiovascular adverse effects at 7 to 22 times the maximum recommended dose. Case reports of overdose with as much as 30 to 50 times the standard dose described the drug as relatively nontoxic, compared to TCAs.

Twelve reported fatalities have been attributed to mirtazapine overdose in literature.[60][61] 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.

On 10 June 2013 Lee Webster was convicted of the manslaughter of Jason Wood at Maidstone Crown Court. He had added 27 mirtazapine tablets to Wood's drink while both were drunk.[63] Wood was a dwarf with a body weight of 6 stone (38 kilogram).

This article uses material from the Wikipedia article Mirtazapine, which is released under the Creative Commons Attribution-Share-Alike License 3.0.