Preventing Depressive Relapse and Recurrence in Higher-Risk Cognitive Therapy Responders

Abstract

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 were randomized and 181 subsequently entered the follow-up. Cognitive therapy responders at higher risk for relapse were randomized to receive 8 months of C-CT (n = 86), fluoxetine (n = 86), or PBO (n = 69). Survival analyses of relapse/recurrence rates, as determined by blinded evaluators using DSM-IV criteria and the Longitudinal Interval Follow-up Evaluation. RESULTS As predicted, the C-CT or fluoxetine groups were significantly less likely to relapse than the PBO group across 8 months. Relapse/recurrence rates for C-CT and fluoxetine were nearly identical during the 8 months of treatment, although C-CT patients were more likely to accept randomization, stayed in treatment longer, and attended more sessions than those in the fluoxetine and PBO groups. Contrary to prediction, relapse/recurrence rates following the discontinuation of C-CT and fluoxetine did not differ. Relapse risk was reduced by both C-CT and fluoxetine in an enriched randomization sampling only CT responders. The preventive effects of C-CT were not significantly more durable than those of fluoxetine after treatment was stopped, suggesting that some higher-risk patients may require alternate longer-term interventions. clinicaltrials.gov Identifiers: NCT00118404, NCT00183664, and NCT00218764.