SSRI versus bupropion effects on symptom clusters in suicidal depression: post hoc analysis of a randomized clinical trial

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: ClinicalTrials.gov identifier: NCT00429169.

Conflict of interest statement

Conflict of Interest: The other authors have no conflicts of interest related to this study.

© Copyright 2013 Physicians Postgraduate Press, Inc.

Figures

Figure 1

Depressed patients' mean score of suicidal ideationa and HDRS-24 factorsb by study week and treatment with paroxetine vs bupropionc footnotes: aSuicidal ideation measured using the Beck Scale for Suicidal Ideation. bHDRS-24 factor content: Psychic Depression = Depressed mood + Guilt + Retardation + Helplessness + Hopelessness + Worthlessness. Loss of Motivation = Work/activities+ Appetite + Libido + Weight loss. Disturbed Thinking = Lack of insight + Depersonalization/derealization + Paranoia + Obsessions/compulsions. Anxiety = Agitation + Psychic anxiety + Somatic anxiety + Hypochondriasis. Sleep = Insomnia early + Insomnia middle + Insomnia late. cError bars represent standard error of the mean. Paroxetine (N=36) and bupropion (N=38) sample sizes decreased over time due to drop-out (see Table 1).

Figure 2

Depressed patients' mean score on BDI factorsa by study week and treatment with paroxetine vs bupropionb footnotes: aBeck Depression Inventory factor content: Subjective Depression = Sadness + Pessimism + Lack of satisfaction + Loss of interest + Indecisiveness + Appearance + Work + Tiredness + Libido. Self-Blame = Failure + Guilt + Feel Punished + Disappointed in Self + Self-blame. Somatic = Disturbed sleep + Appetite + Weight loss. bError bars represent standard error of the mean. Paroxetine (N=36) and bupropion (N=38) sample sizes decreased over time due to drop-out (see Table 1).