Mirtazapine

For a more detailed discussion of this topic, see Mirtazapine, Sec. 31.21, p. 3152, in Comprehensive Textbook of Psychiatry, 9th Edition.

Mirtazapine (Remeron) is unique among drugs used to treat major depression in that it increases both norepinephrine and serotonin through a mechanism other than reuptake blockade (as in the case of tricyclic agents or selective serotonin reuptake inhibitors [SSRIs]) or monoamine oxidase inhibition (as in the case of phenelzine or tranylcypromine). Mirtazapine is also more likely to reduce rather than cause nausea and diarrhea, the result of its effects on serotonin 5-HT₃ receptors. Characteristic side effects include increased appetite and sedation.

Pharmacologic Actions

Mirtazapine is administered orally and is rapidly and completely absorbed. It has a half-life of about 30 hours. Peak concentration is achieved within 2 hours of ingestion, and steady state is reached after 6 days. Plasma clearance may be slowed up to 30% in persons with impaired hepatic function, up to 50% in those with impaired renal function, up to 40% slower in elderly men, and up to 10% slower in elderly women.

The mechanism of action of mirtazapine is antagonism of central presynaptic α₂-adrenergic receptors and blockade of postsynaptic serotonin 5-HT₂ and 5-HT₃ receptors. The α₂-adrenergic receptor antagonism causes increased firing of norepinephrine and serotonin neurons. The potent antagonist of serotonin 5-HT₂ and 5-HT₃ receptors serves to decrease anxiety, relieve insomnia, and stimulate appetite. Mirtazapine is a potent antagonist of histamine H₁ receptors and is a moderately potent antagonist at α₁-adrenergic and muscarinic-cholinergic receptors.

Therapeutic Indications

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