Mirtazapine is a novel antidepressant with a unique mode of action, which can be best summarized as a noradrenaline and specific serotonin antidepressant. Its unique mode of action, involving both the noradrenergic and serotonergic neurotransmitter systems, results in strong clinical efficacy. A comprehensive clinical trial programme in Europe and the United States has demonstrated that mirtazapine has clear clinical benefits in a broad range of patients treated across different therapeutic settings. The individual placebo-controlled trials and a meta-analysis on pooled efficacy data from all available placebo-controlled studies have shown that mirtazapine has sustained antidepressant efficacy, as assessed by changes from baseline in group mean scores on the Hamilton Rating Scale for Depression (HAMD) and in the depressed mood item, from week 1 throughout the whole study period. Corroborative evidence on the clinical efficacy of mirtazapine has been obtained in comparative studies with antidepressant drugs of well established efficacy, such as amitriptyline, clomipramine, doxepin and trazodone. As with the placebo-controlled studies, a meta-analysis was performed on data from all the randomized, double-blind, comparative studies of mirtazapine and amitriptyline. Data from 732 patients were available (364 patients taking mirtazapine and 368 taking amitriptyline) for efficacy analysis. Equivalent improvements in total 17-item HAMD scores from baseline were observed in both treatment groups at all scheduled assessments and at the end of the study period, and similarly high percentages of patients responded to treatment with either mirtazapine (70%) or amitriptyline (73%). The efficacy of mirtazapine was also assessed in the treatment of moderately (baseline 17-item HAMD score 18-24) or severely depressed patients (baseline 17-item HAMD score > or = 25). A meta-analysis was performed on the pooled data from the moderately or severely depressed patients in the comparative studies of mirtazapine and placebo or mirtazapine and amitriptyline. Statistically and clinically significant improvements from baseline were seen in both moderately and severely depressed patients treated with mirtazapine compared with placebo, while an equivalent extent of improvement was present with mirtazapine and amitriptyline. A similar pattern was observed in the improvement of depressed mood (HAMD item 1) and other clinically important symptoms of depression: mirtazapine was significantly more efficacious than placebo, and of equivalent efficacy to amitriptyline. Therefore, it can be concluded that the new antidepressant mirtazapine offers distinct therapeutic benefits for a variety of depressed patients in either in- or outpatient settings.
