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.