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=36) or bupropion (N=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=0.02); and (2) in a separate model adjusted for baseline depression, for suicidal ideation measured with the Beck Scale for Suicidal Ideation (p=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 patients—an important public health population—this preliminary finding merits further study.
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Acknowledgements
This study was initiated with a NARSAD Young Investigator grant (Grunebaum) and completed under National Institute of Mental Health K23 MH076049 (Grunebaum). Other support included National Institute of Mental Health Grants MH48514 and MH62185. We thank all the hard-working research team members and the brave patients who participated in this study.
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To defray costs, Paxil CR and Wellbutrin XL pills were donated by GlaxoSmithKline in the first 3 years of this study and were purchased with grant funds thereafter. Dr Mann received research grant support for unrelated brain imaging studies from GlaxoSmithKline and Novartis. Dr Duan received research support from Pfizer for unrelated health services research. The other authors declare no conflict of interest.
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The sponsors (NARSAD and NIMH) had no role in the design and conduct of the study; the collection, analysis, and interpretation of the data; or the preparation, review, or approval of the manuscript. They had no access to the data or any editorial role in this manuscript.
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Grunebaum, M., Ellis, S., Duan, N. et al. Pilot Randomized Clinical Trial of an SSRI vs Bupropion: Effects on Suicidal Behavior, Ideation, and Mood in Major Depression. Neuropsychopharmacol 37, 697–706 (2012). https://doi.org/10.1038/npp.2011.247
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DOI: https://doi.org/10.1038/npp.2011.247
