Mirtazapine is an antidepressant introduced by Organon International in 1996 used for the treatment of moderate to severe depression. Mirtazapine has a tetracyclic chemical structure and is classified as a noradrenergic and specific serotonergic antidepressant (NaSSA). Mirtazapine and Ludiomil are the only tetracyclic antidepressants that have been approved by the U.S. Food and Drug Administration to treat depression. Because of its unique pharmacologic profile, mirtazapine is virtually devoid of anticholinergic effects, serotonin-related side effects, and adrenergic side effects (orthostatic hypotension and sexual dysfunction). Antihistaminic side effects of drowsiness and weight gain are prominent. It is most useful as an add-on medication to enhance the effectiveness of agents such as duloxetine and venlafaxine in severe and treatment-resistant depression. Mirtazapine is relatively safe if an overdose is taken.