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Original Research

SSRI Versus Bupropion Effects on Symptom Clusters in Suicidal Depression: Post Hoc Analysis of a Randomized Clinical Trial

Michael F. Grunebaum, MD; John G. Keilp, PhD; Steven P. Ellis, PhD; Katherin Sudol, BA; Neal Bauer, MA; Ainsley K. Burke, PhD; Maria A. Oquendo, MD; and J. John Mann, MD

Published: September 15, 2013

Article Abstract

Objective: Identifying the depression symptoms most closely associated with suicidal thoughts and which medications provide the fastest depression relief may help suicide prevention.

Method: Post hoc analysis of data from a randomized, double-blind, 8-week clinical trial of the selective serotonin reuptake inhibitor paroxetine controlled release (n = 36) versus the norepinephrine-dopamine reuptake inhibitor bupropion extended release (n = 38) was conducted in patients with DSM-IV major depressive disorder and past suicide attempt or current suicidal thoughts. Treatment effects on Hamilton Depression Rating Scale (HDRS) and Beck Depression Inventory symptom clusters were compared. We hypothesized that paroxetine would demonstrate a superior effect on nonsuicidal, affective/cognitive depression symptom clusters that our prior work found to be associated with suicidal thoughts and attempts. Data were collected from February 2005 to January 2010.

Results: There was a treatment main effect on HDRS psychic depression (depressed mood, guilt, retardation, helpless, hopeless, worthless) (estimate = −2.2; 95% CI, −3.2 to −1.1; t67.16 = −4.01; P < .001), one of the clusters most strongly correlated to suicidal ideation. The net drug effect demonstrated that mean psychic depression score was 2.2 points lower after 1 week of paroxetine compared to bupropion treatment. The significance level of this effect was P < .001 at weeks 1 and 2, P = .012 at week 3 and P = .051 at week 4. Results for other depression scale factors were nonsignificant (P > .05).

Conclusions: The results require replication but suggest a pathway by which selective serotonin reuptake inhibitor treatment may exert a stronger effect compared with norepinephrine-dopamine reuptake inhibitor treatment on reduction of suicidal thoughts during initial weeks of pharmacotherapy in these higher risk patients.

Trial Registration: identifier: NCT00429169.

J Clin Psychiatry 2013;74(9):872-879

Submitted: July 5, 2012; accepted December 19, 2012 (doi:10.4088/JCP.12m08000).

Corresponding author: Michael F. Grunebaum, MD, Molecular Imaging and Neuropathology Division, New York State Psychiatric Institute, 1051 Riverside Drive, Box 42, New York, NY 10032 (

Volume: 74

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