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Original Investigation |

Preventing Depressive Relapse and Recurrence in Higher-Risk Cognitive Therapy Responders:  A Randomized Trial of Continuation Phase Cognitive Therapy, Fluoxetine, or Matched Pill Placebo

Robin B. Jarrett, PhD1; Abu Minhajuddin, PhD2; Howard Gershenfeld, MD, PhD1; Edward S. Friedman, MD3; Michael E. Thase, MD3,4,5
[+] Author Affiliations
1Department of Psychiatry, The University of Texas Southwestern Medical Center, Dallas
2Department of Clinical Sciences, The University of Texas Southwestern Medical Center, Dallas
3Department of Psychiatry, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
4Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia
5Department of Psychiatry Philadelphia Veterans Affairs Medical Center, Pennsylvania
JAMA Psychiatry. 2013;70(11):1152-1160. doi:10.1001/jamapsychiatry.2013.1969.
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Importance  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.

Objectives  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.

Design  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.

Setting  Two university-based specialty clinics.

Patients  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.

Interventions  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).

Main Outcomes and Measures  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.

Conclusions and Relevance  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.

Trial Registration  clinicaltrials.gov Identifiers: NCT00118404, NCT00183664, and NCT00218764

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Figure 1.
Consort Flow Diagram

CT indicates cognitive therapy; C-CT, continuation phase cognitive therapy.

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Figure 2.
Kaplan-Meier Survival Curves

Curves estimate the time from randomization into the continuation phase until relapse/recurrence (DSM-IV major depressive disorder diagnosed by blind evaluator). Log-rank tests comparing outcomes across the 8-month (35-week) continuation phase therapies revealed that the proportion of relapse in continuation phase cognitive therapy (C-CT) (18.3%; n = 86) or fluoxetine (18.0%; n = 86) were significantly less than in pill placebo (PBO) (32.7%; n = 69). Pairwise contrasts were as follows: fluoxetine vs PBO: χ21 = 3.92, P = .02; C-CT vs PBO: χ21 = 3.39, P = .03; and C-CT vs fluoxetine: χ21 = 0.04, P = .42. Across the subsequent follow-up, log-rank tests with pairwise comparisons showed no differences among treatments at 24 or 32 months postrandomization.

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