CNS Drugs

, Volume 19, Issue 2, pp 137–146

Comparison of the Effects of Mirtazapine and Fluoxetine in Severely Depressed Patients

  • Marcio Versiani
  • Ricardo Moreno
  • Catharina J. A. Ramakers-van Moorsel
  • Albert J. Schutte
Original Research Article

DOI: 10.2165/00023210-200519020-00004

Cite this article as:
Versiani, M., Moreno, R., Ramakers-van Moorsel, C.J.A. et al. CNS Drugs (2005) 19: 137. doi:10.2165/00023210-200519020-00004


Introduction: Depression is a major global problem associated with large medical, sociological and economic burdens. Mirtazapine (Remeron®, Organon NV, The Netherlands) is an antidepressant with a unique mechanism of action that has similar or superior efficacy to TCAs and SSRIs in moderate-to-severe depression. However, this agent has not yet been tested in patients with severe depression alone.

Objective: To compare the antidepressant efficacy and tolerability of mirtazapine and fluoxetine and their effects on anxiety and quality of life in patients with severe depression (≥25 points on the first 17 items of the Hamilton Depression Rating Scale [HDRS-17]).

Methods: In this double-blind study, 297 severely depressed patients were randomised to receive mirtazapine 15–60 mg/day (n = 147) or fluoxetine 20–40 mg/day (n = 152) for 8 weeks. 294 subjects were actually treated and 292 included in the intent-to-treat population. Symptom severity was measured by the HDRS-17, Montgomery-Asberg Depression Rating Scale (MADRS) and Clinical Global Impression (CGI) rating scale. Quality of life was self-assessed by patients using the Leeds Sleep Evaluation Questionnaire and the Quality of Life, Enjoyment and Satisfaction Questionnaire. Adverse events were recorded throughout the study.

Results: No statistically significant differences were noted between the two groups in change from baseline HDRS-17 score at any time point; both treatments were associated with large (∼15 points) decreases by study end. However, more mirtazapine-treated patients tended to exhibit a ≥50% decrease in HDRS score (significant at day 7; 9.0% vs 0.7%, p = 0.002). Significant differences in favour of mirtazapine were also observed at day 14 for changes in MADRS scores (−10.9 vs −8.5, p = 0.006) and the proportion of patients with ≥50% decrease in MADRS score (21.4% vs 10.9%, p = 0.031). On the CGI, the proportion of ‘much/very much improved’ patients tended to be greater with mirtazapine (significant at day 7; 9.7% vs 3.4%, p = 0.032). No significant between-group differences were observed for the majority of quality-of-life measures. However, mirtazapine produced significantly better improvements on ‘sleeping assessment 1’ (14.9 ± 5.2 vs 13.7 ± 5.4, p = 0.028) and ‘sleeping assessment 2’ (p = 0.013) than fluoxetine. Both agents were generally well tolerated but mirtazapine-treated patients experienced a mean weight gain of 0.8 ± 2.7kg compared with a mean decrease in weight of 0.4 ± 2.1kg for fluoxetine-treated patients (p < 0.001).

Conclusions: Mirtazapine is as effective and well tolerated as fluoxetine in the treatment of patients with severe depression.

Copyright information

© Adis Data Information BV 2005

Authors and Affiliations

  • Marcio Versiani
    • 1
  • Ricardo Moreno
    • 2
  • Catharina J. A. Ramakers-van Moorsel
    • 3
  • Albert J. Schutte
    • 4
  1. 1.Institute of PsychiatryFederal University of Rio de JaneiroRio de JaneiroBrazil
  2. 2.Affective Disorders Study Group (GRUDA)University of São PauloSão PauloBrazil
  3. 3.Clinical Trial Operations, Organon NVOssThe Netherlands
  4. 4.Medical Services CNSOrganon International Inc.RoselandUSA

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