Pilot Randomized Clinical Trial of an SSRI vs Bupropion: Effects on Suicidal Behavior, Ideation, and Mood in Major Depression

Abstract

Randomized controlled trials in depressed patients selected for elevated suicidal risk are rare. The resultant lack of data leaves uncertainty about treatment in this population. This study compared a serotonin reuptake inhibitor with a noradrenergic/dopaminergic antidepressant in major depression with elevated suicidal risk factors. We conducted a double-blind, randomized, clinical pilot trial of paroxetine (N ¼ 36) or bupropion (N ¼ 38) in DSM IV major depression with a suicide attempt history or current suicidal ideation. The effects during acute (8 weeks) and continuation treatment (up to 16 weeks) were measured. Main outcomes were suicidal behavior and ideation. The secondary outcome was modified 17-item Hamilton Depression Rating Scale score subtracting the suicide item (mHDRS-17). Treatment was not associated with time to a suicidal event and no treatment main effect or treatment  time interaction on suicidal ideation or mHDRS-17 was found. Exploratory model selection showed modest advantages for paroxetine on: (1) mHDRS-17 (p ¼ 0.02); and (2) in a separate model adjusted for baseline depression, for suicidal ideation measured with the Beck Scale for Suicidal Ideation (p ¼ 0.03), with benefit increasing with baseline severity. Depressed patients with greater baseline suicidal ideation treated with paroxetine compared with bupropion appeared to experience greater acute improvement in suicidal ideation, after adjusting for global depression. Given the lack of evidence-based pharmacotherapy guidelines for suicidal, depressed patientsFan important public health populationFthis preliminary finding merits further study.

SSRI Versus Bupropion Effects on Symptom Clusters in Suicidal Depression

“…The results partially support our hypothesis that an SSRI, which appears potentially advantageous compared to bupropion for reducing suicidal ideation among those most suicidal at baseline, 33 would also be superior for non-suicide depression symptoms that are more closely associated with suicidal ideation. 32 If confirmed, this would help guide treatment choice for more suicidal patients where faster reduction of suicidal risk would be a major clinical advantage.…”

“…33 The treatment groups did not differ in study attrition rate, medication adherence, side effects, or frequency of concomitant benzodiazepine or zolpidem, although benzodiazepine dose was higher in the bupropion treated group. 33 Figures 1 and 2 illustrate the trajectories of SSI score and the HDRS and BDI depression factors by treatment during the trial.…”

“…The findings require replication, but suggest a possible mechanism for the reported advantage of SSRI for suicidal ideation. 33 …”

“…33 Briefly, patients 18 to 75 years old with current DSM-IV major depressive disorder (MDD), scoring 16 or greater on the HDRS-17, 11 and with either a past suicide attempt or current suicidal ideation or both were eligible. Minimum ideation for non-attempters was a score of 2 or greater on HDRS item 3 (suicide), “wishes to be dead or has any thoughts of possible death to self.” 11 Exclusions were: bipolar disorder, psychosis, anorexia or bulimia nervosa, current SSRI or bupropion use for other indications (e.g.…”

“…33 Serotonin reuptake inhibitors (SSRI), including paroxetine, primarily enhance serotonin neurotransmission, while bupropion is a norepinephrine-dopamine reuptake inhibitor (NDRI) with minimal (or no) direct effects on serotonin. 34 Understanding the reasons for this differential drug effect on suicidal ideation could potentially enhance clinical care for suicidal patients.…”