Comparative efficacy and durability of continuation phase cognitive therapy for preventing recurrent depression: Design of a double-blinded, fluoxetine- and pill placebo-controlled, randomized trial with 2-year follow-up

Abstract

Background Major Depressive Disorder (MDD) is highly prevalent and associated with disability and chronicity. Although cognitive therapy (CT) is an effective short-term treatment for MDD, a significant proportion of responders subsequently suffer relapses or recurrences. Purpose This design prospectively evaluates: 1) a method to discriminate CT-treated responders at lower vs. higher risk for relapse; and 2) the subsequent durability of 8-month continuation phase therapies in randomized higher risk responders followed for an additional 24 months. The primary prediction is: after protocol treatments are stopped, higher risk patients randomly assigned to continuation phase CT (C-CT) will have a lower risk of relapse/recurrence than those randomized to fluoxetine (FLX). Methods Outpatients, aged 18 to 70 years, with recurrent MDD received 12–14 weeks of CT provided by 15 experienced therapists from two sites. Responders (i.e., no MDD and 17-item Hamilton Rating Scale for Depression ≤ 12) were stratified into higher and lower risk groups based on stability of remission during the last 6 weeks of CT. The lower risk group entered follow-up for 32 months; the higher risk group was randomized to 8 months of continuation phase therapy with either C-CT or clinical management plus either double-blinded FLX or pill placebo. Following the continuation phase, higher risk patients were followed by blinded evaluators for 24 months. Results The trial began in 2000. Enrollment is complete ( n = 523). The follow-up continues. Conclusions The trial evaluates the preventive effects and durability of acute and continuation phase treatments in the largest known sample of CT responders collected worldwide.