The results of 3 completed comparative studies of mirtazapine versus selective serotonin reuptake inhibitors (SSRIs; fluoxetine, paroxetine, and citalopram) are reviewed. The studies aimed to compare efficacy and tolerability in acute treatment of inpatients and outpatients with major depressive disorder. In comparative trials with fluoxetine, patients who had high baseline total 17-item Hamilton Rating Scale for Depression (HAM-D) and depressed mood item scores were included (scores ≥ 21 and ≥ 2, respectively). In the comparative trials with citalopram and paroxetine, the inclusion criteria were total Montgomery-Asberg Depression Rating Scale (MADRS) score ≥ 22 and 17-item HAM-D score ≥ 18. In all 3 studies, statistically significant and clinically relevant differences in favor of mirtazapine were evident on several outcome variables. Against citalopram and paroxetine, the differences in antidepressant efficacy were registered early in treatment but not later, thus suggesting potentially faster onset of efficacy of mirtazapine. These differences were demonstrated on both the 17-item HAM-D and MADRS scales. In addition, mirtazapine demonstrated an accelerated anxiolytic effect as shown by changes from baseline on the Hamilton Rating Scale for Anxiety. Tolerability of all studied compounds was very good, as reflected in a low percentage of premature terminations due to adverse events. On the other hand, differences in pharmacologic profiles between mirtazapine and SSRIs were reflected in their adverse events profiles. The results of these studies confirm that mirtazapine displays good efficacy—leading to an early relief of symptoms—in combination with good tolerability. ‘ ‹
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