Mirtazapine is at least as effective as the tricyclic antidepressants and trazodone in a wide range of patient subgroups including in- and out-patients with moderate to severe depression. It also appears to be at least as effective as the serotonin and noradrenaline reuptake inhibitor venlafaxine in the treatment of severely depressed melancholic patients. When compared with the selective serotonin reuptake inhibitors (SSRIs), mirtazapine shows a significantly earlier onset of action. Further analysis of a study comparing mirtazapine with the SSRI paroxetine indicated that early improvement was a highly sensitive predictor of later stable response for both drugs. The positive predictive value of an early improvement was significantly higher during mirtazapine treatment compared with paroxetine. The negative predictive value approached maximum values as early as week 2 with mirtazapine and week 3 with paroxetine. This suggests that the predictability of the response to treatment is better with mirtazapine than with paroxetine.