BACKGROUND: Relapse rates may be as high as 50% in people with major depressive disorder (MDD) previously treated to remission. AIMS: Duloxetine, an inhibitor of serotonin and noradrenaline reuptake that is licensed in Europe, the USA and elsewhere for the treatment of depressive episodes, was evaluated with regard to its efficacy, safety and tolerability in the prevention of relapse of MDD. METHOD: Adult out-patients with MDD received duloxetine (60 mg daily) for 12 weeks (n=533). Patients who responded to the drug were then randomised to duloxetine(60 mg daily)(n=136) or or placebo placebo (n=142) for 26 weeks. The primary measure of efficacy was time to relapse. RESULTS: Patients who received duloxetine (60 mg daily) experienced significantly longer times to relapse of MDD, and better efficacy, global well-being, and quality-of-life outcomes compared with patients who received placebo. It should be noted that adverse events which occur in discontinuation may mimic some signs of depressive relapse, and were not specifically elicited in this study. CONCLUSIONS: Duloxetine (60 mg daily) is effective in the prevention of relapse of MDD during continuation treatment.