Mirtazapine and Depressions

Abstract

Mirtazapine was introduced into the United States in 1996 as a norepinephrine and specific serotonergic antidepressant which would have a broad spectrum of activity and hopefully fewer side effects compared with selective serotonin reuptake inhibitors. Mirtazapine consists of S- and R-enantiomers which are metabolized by cytochromes CYP1A2, CYP2D6, and CYP3A4 which are then glucuronidated. Metabolites account for only 10% of mirtazapine antidepressant activity. Oral bioavailability is approximately 50% and half-life 20-40 h. Mirtazapine inhibits presynaptic alpha-2 adrenergic autoreceptors, presynaptic alpha-2 adrenergic heteroreceptors, and two postsynaptic serotonin receptors, 5 HT-2 and 5 HT-3. Mirtazapine labeled indication for treatment of outpatient major depressive disorder. Mirtazapine responses were noted to occur within 1 week of starting therapy and differ significantly from placebo. Responses are equivalent to amitriptyline and, in some reviews, superior to selective serotonin reuptake inhibitors. Mirtazapine appears to be a very cost-effective antidepressant when weighing, response, tolerance, and drug costs. Major side effects are sedation and weight gain. Mirtazapine transiently impairs driving skills. Hyponatremia, sexual dysfunction, and seizure risks are lower with mirtazapine than seen with SSRIs. There are relatively few drug-drug interactions. Mirtazapine has been combined with SSRIs to augment SSRI antidepressant responses. It is the most frequently used antidepressant by survey used to treat depression in cancer.