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Strategies to improve the course of recurrent major depressive disorder have great public health relevance. To reduce the risk of relapse/recurrence after acute phase cognitive therapy (CT), a continuation phase model of therapy may improve outcomes.

To test the efficacy of continuation phase CT (C-CT) and fluoxetine for relapse prevention in a pill placebo (PBO)–controlled randomized trial and compare the durability of prophylaxis after discontinuation of treatments.

A sequential, 3-stage design with an acute phase (all patients received 12 weeks of CT); 8-month experimental phase (responders at higher risk were randomized to C-CT, fluoxetine, or PBO); and 24 months of longitudinal, posttreatment follow-up.

Two university-based specialty clinics.

A total of 523 adults with recurrent major depressive disorder began acute phase CT, of which 241 higher-risk responders …