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 antagonism 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.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.After one week of usage, mirtazapine was found to have an earlier onset of action compared to SSRIs. Other
There is also some evidence supporting its use in treating the following conditions, for which it is sometimes prescribed off-label:

Doses of mirtazapine used for sleep range from 7.5 to 45 mg. Doses of 7.5 to 15 mg are recommended as mirtazapine may become more stimulating at higher doses.
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Chemistry
Mirtazapine is a tetracyclic piperazinoazepine; mianserin was developed by the same team of organic chemists and mirtazapine differs from it via addition of a nitrogen atom in one of the rings. : 429  It is a racemic mixture of enantiomers. The (S)-(+)-enantiomer is known as esmirtazapine. Analogues of mirtazapine include mianserin, setiptiline, and aptazapine. Synthesis
A chemical synthesis of mirtazapine has been published. The first step of synthesis is a condensation reaction between the molecule 2-chloro 3-cyanopyridine and the molecule 1-methyl-3-phenylpiperazine. History
Mirtazapine was first synthesized at Organon and published in 1989, was first approved for use in major depressive disorder in the Netherlands in 1994, and was introduced in the United States in 1996 under the brand name Remeron. : 429

Society and culture
Generic names
Mirtazapine is the English and French generic name of the drug and its INN, USAN, USP, BAN, DCF, and JAN. Its generic name in Spanish, Italian and Portuguese is mirtazapina and in German and Swedish is Mirtazapin.