Efficacy of mirtazapine for prevention of depressive relapse: A placebo-controlled double-blind trial of recently remitted high-risk patients

Background: The necessity of antidepressant continuation-phase therapy following acute-phase response has resulted in the need to characterize the longer-term efficacy and safety of all new medications. Previous studies using "extension" protocols suggest that mirtazapine has sustained antidepressant effects. The current study was performed to evaluate the efficacy and safety of up to I year of mirtazapine therapy, using a more rigorous, randomized, placebo-controlled discontinuation design. Method: An intent-to-treat sample of 410 patients meeting DSM-IV criteria for moderate-to-severe recurrent or chronic major depressive episodes began 8 to 12 weeks of open-label therapy with mirtazapine (flexibly titrated, 15-45 mg/day). Thereafter, 156 fully remitted patients (according to Hamilton Rating Scale for Depression and Clinical Global Impressions-Improvement scores) were randomly assigned to receive 40 weeks of double-blind continuation-phase therapy with either mirtazapine or placebo. Results: Mirtazapine therapy reduced the rate of depressive relapse by more than half, with 43.8% of patients relapsing on treatment with placebo as compared with 19.7% of the mirtazapine-treated patients. The discontinuation rate due to adverse events was 11.8% for active mirtazapine therapy versus 2.5% for placebo. Although weight gain was significantly greater in the group receiving active medication during the double-blind phase (p = .001), patients taking mirtazapine gained only 1.4 kg (3.1 lb) across the 40 weeks of continuation therapy, and there was no difference in the rates of weight gain as a new-onset adverse event. Conclusion: Continuation-phase therapy with mirtazapine is effective and well tolerated.