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 foll owing acute-phase response has resulted in the need to characterize the lon ger-term efficacy and safety of all new medications. Previous studies using "extension" protocols suggest that mirtazapine has sustained antidepressan t effects. The current study was performed to evaluate the efficacy and saf ety of up to I year of mirtazapine therapy, using a more rigorous, randomiz ed, placebo-controlled discontinuation design. Method: An intent-to-treat sample of 410 patients meeting DSM-IV criteria f or 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 sc ores) were randomly assigned to receive 40 weeks of double-blind continuati on-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 c ompared 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 gr oup receiving active medication during the double-blind phase (p = .001), p atients 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 we ll tolerated.