Mirtazapine: Clinical Overview

There is currently available evidence that suggests that drugs combining 2 synergistic mechanisms of action (e.g., enhancement of both noradrenergic and serotonergic neurotransmission) may yield superior therapeutic efficacy compared with a single therapeutic mechanism of highly selective agents such as selective serotonin reuptake inhibitors (SSRIs). The differences in antidepressant efficacy favoring dual-acting drugs may exist in particular for 3 difficult-to-treat groups of patients: those with endogenous depression, those with severe depression, or hospitalized depressed patients. Mirtazapine differs from other new dual-acting antidepressants by not being a reuptake inhibitor. Its antidepressant activity may be related to a direct enhancement of noradrenergic neurotransmission by blockade of α2-autoreceptors. The rapid increase in serotonin (5-HT) synaptic levels by blockade of α2-heteroreceptors indirectly enhances 5-HT1A-mediated neurotransmission since 5-HT₂ and 5-HT₃ are blocked by mirtazapine. The antidepressant efficacy of mirtazapine was established in several placebo-controlled trials. Currently available evidence suggests that mirtazapine is effective in all levels of severity of depressive illness, as well as is in a broad range of symptoms associated with depression. ‘ ‹’ ‹