Mirtazapine: Efficacy and Tolerability in Comparison With Fluoxetine in Patients With Moderate to Severe Major Depressive Disorder

Objective: To compare the efficacy andtolerability of mirtazapine and fluoxetine in depressedinpatients and outpatients.

Method: Patients with a major depressive episode(DSM-III-R), a baseline score of ž21 on the 17-item HamiltonRating Scale for Depression (HAM-D), and ž2 on HAM-D Item 1(depressed mood) were randomly assigned to a 6-week treatmentwith either mirtazapine (N=66, 15-60 mg/day) or fluoxetine (N=67,20-40 mg/day). The upper limit of the mirtazapine dose range wasabove the dose range approved in the United States (15-45mg/day). Efficacy was evaluated by the HAM-D, Clinical GlobalImpressions, the Visual Analogue Mood Rating Scale (VAMRS), andthe Quality of Life Enjoyment and Satisfaction Questionnaire(QLESQ). The efficacy analyses were performed on theintent-to-treat group using the last-observation-carried-forwardmethod.

Results: Mean total 17-item HAM-D scores atbaseline were 26.0 for the mirtazapine- and 26.1 for thefluoxetine-treated group. The decrease from baseline on the HAM-Dwas larger in the mirtazapine than in the fluoxetine groupthroughout the treatment period, reaching statisticalsignificance at days 21 and 28. At assessments from day 21 andonward, the absolute difference between the 2 study groupsfavoring mirtazapine ranged from 3.7 to 4.2 points, the magnitudeof difference usually seen between an efficacious antidepressantdrug and placebo. Mean dosages at weeks 1-4 were 36.5 mg/day formirtazapine and 19.6 mg/day for fluoxetine; the respectivedosages at weeks 5-6 were 56.3 mg and 35.8 mg. Similar numbers ofpatients dropped out due to adverse events; tolerability profileswere comparable except for changes in body weight from baselinewhich were statistically significantly more pronounced in themirtazapine group compared to the fluoxetine group.

Conclusion: We found that mirtazapine was aswell tolerated as fluoxetine and significantly more effectiveafter 3 and 4 weeks of therapy.