MIRTAZAPINE - EFFICACY AND TOLERABILITY IN COMPARISON WITH FLUOXETINEIN 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 great er than or equal to 21 on the 17-item Hamilton Rating Scale for Depres sion (HAM-D), and greater than or equal to 2 on HAM-D Item 1 (depresse d mood) were randomly assigned to a 6-week treatment with either mirta zapine (N = 66, 15-60 mg/day) or fluoxetine (N = 67, 20-40 mg/day). Th e upper limit of the mirtazapine dose range was above the dose range a pproved in the United States (15-45 mg/day), Efficacy was evaluated by the HAM-D, Clinical Global Impressions, the Visual Analogue Mood Rati ng Scale (VAMRS), and the Quality of Life Enjoyment and Satisfaction Q uestionnaire (QLESQ). The efficacy analyses were performed on the inte nt-to-treat group using the last-observation-carried-forward method. R esults: 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 f rom baseline on the HAM-D was larger in the mirtazapine than in the fl uoxetine group throughout the treatment period, reaching statistical s ignificance at days 21 and 28. At assessments from day 21 and onward, the absolute difference between the 2 study groups favoring mirtazapin e ranged from 3.7 to 4.2 points, the magnitude of difference usually s een between an efficacious antidepressant drug and placebo. Mean dosag es at weeks 1-4 were 36.5 mg/day for mirtazapine and 19.6 mg/day for f luoxetine; the respective dosages at weeks 5-6 were 56.3 mg and 35.8 m g. Similar numbers of patients dropped out due to adverse events; tole rability profiles were comparable except for changes in body weight fr om 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 signif icantly more effective after 3 and 4 weeks of therapy.