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Original Research

Effect of Antidepressant Medication Treatment on Suicidal Ideation and Behavior in a Randomized Trial: An Exploratory Report From the Combining Medications to Enhance Depression Outcomes Study

Sidney Zisook, MD; Ira M. Lesser, MD; Barry Lebowitz, PhD; A. John Rush, MD; Gene Kallenberg, MD; Stephen R.Wisniewski, PhD; Andrew A. Nierenberg, MD; Maurizio Fava, MD; James F.Luther, MA; David W. Morris, PhD; and Madhukar H. Trivedi, MD

Published: October 24, 2011

Article Abstract

Objective: To explore relationships between baseline sociodemographic and clinical features and baseline suicidal ideation, and treatment effects on suicidal ideation and behavior, in depressed outpatients.

Method: From March 2008 to September 2009, the Combining Medications to Enhance Depression Outcomes study, a single-blind, 7-month randomized trial, enrolled outpatients with nonpsychotic chronic and/or recurrent major depressive disorder (DSM-IV-TR criteria) in primary and psychiatric care (N = 665). Participants received escitalopram plus placebo, bupropion sustained release (SR) plus escitalopram, or venlafaxine extended release (XR) plus mirtazapine. The primary outcome measure for this report is presence of suicidal ideation assessed by the Concise Health Risk Tracking Self-Report, which measures suicidal ideation and behaviors over the last 24 hours. Sociodemographic and clinical features were compared in those with versus without baseline ideation. At 4, 12, and 28 weeks, treatment effects on suicidality were assessed, and unadjusted and adjusted outcomes were compared among those with and without baseline ideation using linear, logistic, ordinal logistic, and negative binomial regression models.

Results: Baseline suicidal ideation was associated with greater depressive severity, childhood neglect, childhood abuse, early major depressive disorder onset, greater psychiatric comorbidity, and worse functioning and quality of life. After adjustment for treatment, gender, age at first depressive episode, obsessive-compulsive symptoms, and depressive severity, depressive symptom outcomes did not differ between ideation groups at 12 or 28 weeks or between treatments. Overall, 79% of participants with baseline suicidal ideation had none at week 4, 83% had none at week 12, and 86% had none at week 28. All treatments reduced ideation, with bupropion-SR plus escitalopram the most effective at week 12 (P < .01). In participants without baseline ideation, emergent ideation did not differ between treatments: 2.5% had ideation at 4 weeks, 1.3% had ideation at 12 weeks, and only 1.7% had ideation at 28 weeks. Four patients (all receiving venlafaxine-XR plus mirtazapine) attempted suicide (P = .0162).

Conclusion: Baseline ideation did not affect depressive symptom outcome. Bupropion-SR plus escitalopram most effectively reduced ideation. Ideation emergence was uncommon. Venlafaxine-XR plus mirtazapine may pose a higher risk of suicide attempts.

Trial Registration: Identifier: NCT00590863

J Clin Psychiatry 2011;72(10):1322-1332

Submitted: November 17, 2010; accepted August 1, 2011(doi:10.4088/JCP.10m06724).

Corresponding author: Sidney Zisook, MD, VA Healthcare System, 3350 La Jolla Village Dr, San Diego, CA 92161 (

Volume: 72

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