BackgroundMajor depression is highly recurrent. Antidepressant maintenance treatment has proven efficacy against recurrent depression.AimsComparison of prophylactic efficacy of citalopram versus placebo in unipolar, recurrent depression.MethodsPatients 18–65 years of age with recurrent unipolar major depression (DSM–IV), a Montgomery–åsberg Depression Rating Scale score of ≥ 22 and two or more previous depressive episodes, one within the past 5 years, were treated openly with citalopram (20–60 mg) for 6–9 weeks and, if responding, continued for 16 weeks before being randomised to double-blind maintenance treatment with citalopram or placebo for 48–77 weeks.ResultsA total of 427 patients entered acute treatment and 269 were randomised to double-blind treatment. Time to recurrence was longer in patients taking citalopram than in patients taking placebo (P < 0.001). Prophylactic treatment was well tolerated.ConclusionsCitalopram (20, 40 and 60 mg) is effective in the prevention of depressive recurrences. Patients at risk should continue maintenance treatment at the dose necessary to resolve symptoms in the acute treatment phase.