Mirtazapine: Efficacy and tolerability in comparison with fluoxetine in patients with moderate to severe major depressive disorder

Objective: To compare the efficacy and tolerability of mirtazapine and fluoxetine in depressed inpatients and outpatients. Method: Patients with a major depressive episode (DSM-III-R), a baseline score of greater than or equal to 21 on the 17-item Hamilton Rating Scale for Depression (HAM-D), and greater than or equal to 2 on HAM-D Item 1 (depressed mood) were randomly assigned to a 6-week treatment with either mirtazapine (N = 66, 15-60 mg/day) or fluoxetine (N = 67, 20-40 mg/day). The upper limit of the mirtazapine dose range was above the dose range approved in the United States (15-45 mg/day), Efficacy was evaluated by the HAM-D, Clinical Global Impressions, the Visual Analogue Mood Rating Scale (VAMRS), and the Quality of Life Enjoyment and Satisfaction Questionnaire (QLESQ). The efficacy analyses were performed on the intent-to-treat group using the last-observation-carried-forward method. Results: Mean total 17-item HAM-D scores at baseline were 26.0 for the mirtazapine- and 26.1 for the fluoxetine-treated group. The decrease from baseline on the HAM-D was larger in the mirtazapine than in the fluoxetine group throughout the treatment period, reaching statistical significance at days 21 and 28. At assessments from day 21 and onward, the absolute difference between the 2 study groups favoring mirtazapine ranged from 3.7 to 4.2 points, the magnitude of difference usually seen between an efficacious antidepressant drug and placebo. Mean dosages at weeks 1-4 were 36.5 mg/day for mirtazapine and 19.6 mg/day for fluoxetine; the respective dosages at weeks 5-6 were 56.3 mg and 35.8 mg. Similar numbers of patients dropped out due to adverse events; tolerability profiles were comparable except for changes in body weight from baseline which were statistically significantly more pronounced in the mirtazapine group compared to the fluoxetine group. Conclusion: We found that mirtazapine was as well tolerated as fluoxetine and significantly more effective after 3 and 4 weeks of therapy.