A Short Note On The Major Depressive Disorder ( Mdd )

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I. FDA Approved Indications o Major Depressive Disorder (MDD)
Off-Label Uses o Treatment of comorbid insomnia in patients with MDD or other mood disorders o Reduction of hot flash frequency and/or severity in women with natural menopause and those with a history of breast cancer (2)

II. Pharmacology/Pharmacokinetics
a. Therapeutic category: Tetracyclic antidepressant agent
b. Mechanism of action
i. The exact mechanism of antidepressant action of mirtazapine is not entirely understood, but the drug appears to primarily act as an antagonist at central presynaptic α2-adrenergic autoreceptors and heteroreceptors, which inhibits negative feedback to the presynaptic nerve and causes an increase in norepinephrine and serotonin release.
c. Absorption/Distribution/Metabolism/Excretion
i. Absorption is rapid and complete, with approximately 50% bioavailability. ii. Serum levels peak in approximately 2 hours and half-life is 20 to 40 hours (but increased with renal or hepatic impairment). iii. The onset of antidepressant actions can occur within 1—2 weeks, with maximal therapeutic efficacy within 2—4 weeks following the selection of an effective dose. iv. Mirtazapine is 85% bound to protein and extensively metabolized in the liver via cytochrome P450 enzymes 1A2, 2D6, 3A4, and via demethylation and hydroxylation.
v. Mirtazapine is excreted primarily in the urine (75%), but also is eliminated in the feces (15%) as metabolites. (2)
d. Drug Interactions (drug-drug/drug-disease)
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