Recovery and subsequent recurrence in patients with recurrent major depressive disorder

• Type of Material: Article
• Authors: Boadie W Dunlop, Emory University; Peter Holland, Florida Atlantic University; Weihang Bao, Pfizer Inc; Philip T. Ninan, Pfizer Inc; Martin B. Keller, Brown University
• Language: English
• Date: 2012-06
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2012 Elsevier Ltd. All rights reserved.
• License: Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.1016/j.jpsychires.2012.03.002
• Title of Journal or Parent Work: Journal of Psychiatric Research
• ISSN: 0022-3956
• Volume: 46
• Issue: 6
• Start Page: 708
• End Page: 715
• Grant/Funding Information: In the past three years, Dr. Keller has received research grants from Wyeth and Pfizer.; Dr. Holland has received research support from Forest Research Institute, Novartis, Takeda, Cyberonics, Eli Lilly and Genentech.; This study and the statistical analysis for this manuscript were sponsored by Wyeth, which was acquired by Pfizer in October 2009.; In the past 3 years, Dr. Dunlop has received research support from AstraZeneca, BMS, Forest, GSK, Pfizer, Transcept and Wyeth.
• Keywords: Recurrence; Antidepressants; Venlafaxine; Placebo; Forecasting
• Research Categories: Health Sciences, Medicine and Surgery; Psychology, General

Abstract

In contrast to “remission” from an episode of major depressive disorder (MDD), for which there is general agreement in the literature, the optimal definition of “recovery” from MDD is uncertain. Previous definitions of recovery have used inconsistent thresholds for symptom severity and duration of wellness. To address the effects of duration and degree of recovery from an episode of MDD on recurrence risk, and the impact of maintenance antidepressant treatment on recurrence, we analyzed 258 patients from a randomized, double-blind study of outpatients with recurrent MDD. All patients had responded to 8½ months of venlafaxine extended release and were subsequently randomized to receive venlafaxine ER or placebo during 2 consecutive 12-month maintenance phases. Four definitions of recovery were used to evaluate recovery rates and time to recurrence: (1) 17-item Hamilton Depression Rating Scale (HAM-D17) total score ≤3 with duration ≥120 days; (2) HAM-D17 ≤3 with duration ≥56 days; (3) HAM-D17 ≤7 with duration ≥120 days; and (4) HAM-D17 ≤7 with duration ≥56 days. Recovery definitions using lower symptom severity and longer duration thresholds produced lower rates of recurrence. Patients on placebo were more likely to have a recurrence than patients on venlafaxine ER, with hazard ratio (HR) ranging from 2.5 among patients who recovered by the most relaxed criteria (definition 4), to 5.3 among patients who recovered by the most stringent criteria (definition 1). We conclude that protection against recurrence derives from the degree and duration of recovery, particularly for patients maintained on antidepressant medication.