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Cited by 79Treatment of Major DepressionSuicide and Self-Harm StudiesBipolar Disorder and Treatment

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

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Grunebaum, Michael F, Ellis, Steven P, Duan, Naihua, Burke, Ainsley K, Oquendo, Maria A, John Mann, J·2012·Neuropsychopharmacology
DOI 10.1038/npp.2011.247PMC PMC3260969
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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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  • Antidepressants reduced suicidal ideation in 9 of 12 studies that reported effects on suicidal ideation.

    “More promisingly, antidepressants reduced suicidal ideation in 9/12 studies that reported effects on suicidal ideation.(55, 57, 59–65)”

    From Improving Suicide Prevention Through Evidence-Based Strategies: A Systematic Review (2021) · cites this paper as [59]

    The Discussion reports exploratory evidence of greater improvement in suicidal ideation with paroxetine than bupropion among patients with more severe baseline ideation. The Introduction summarizes 10 studies comparing antidepressant classes, but neither section reports that antidepressants reduced ideation in 9 of 12 studies. No page numbers are available in our copy. (LLM, conf=0.82)

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  • SSRIs appeared more effective than noradrenergic drugs for suicidal ideation.

    “SSRIs target serotonin, and appeared more effective than noradrenergic drugs for suicidal ideation.(59, 61)”

    From Improving Suicide Prevention Through Evidence-Based Strategies: A Systematic Review (2021) · cites this paper as [59]

    The Discussion (page not provided) reports an exploratory finding that patients with more severe baseline suicidal ideation improved more on the SSRI paroxetine than on bupropion. It also says the primary treatment effects were not significant. The claim omits those limits and generalizes a comparison of two drugs to SSRIs and noradrenergic drugs as classes. (LLM, conf=0.86)

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  • Of 10 studies that compared the effects of serotonergic antidepressants to noradrenergic antidepressants on suicidal ideation, five favored serotonergic drugs, one favored a noradrenergic drug, and four found no difference.

    “In fact, of 10 such studies that compared the effects of serotonergic antidepressants to noradrenergic antidepressants on suicidal ideation, five studies favored serotonergic drugs 316-320 , one study favored a noradrenergic drug 321 , and four studies found no difference 322-325 .”

    From Suicide and suicide risk (2019) · cites this paper as [325]

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  1. [45]45. Saunders K, Simon G, Bush T, Grothaus L (1998). Assessing the feasibility of using computerized pharmacy refill data to monitor antidepressant treatment on a population basis: a comparison of automated and self-report data. J Clin Psychiatry 51: 883-890.
  2. [47]47. Spitzer RL, Williams JBW, Gibbon M, First MB (1990). Structured Clinical Interview for DSM-III-R/DSM-IV Patient Edition (SCID-P). American Psychiatric Press: Washington, DC.

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Authors
Grunebaum, M. F., Ellis, S. P., Duan, N., Burke, A. K., Oquendo, M. A., & John Mann, J.
Affiliations
New York State Psychiatric Institute (US)
Corresponding author
Grunebaum, Michael F
ORCID
Venue
Neuropsychopharmacology
Publisher
Springer Science and Business Media LLC
Published
2011-10-12
Volume
37
Issue
3
Pages
697-706
ISSN
  • 0893-133X (ISSN-L)
  • 1740-634X
DOI
10.1038/npp.2011.247
PMC
PMC3260969
OpenAlex
W2038804406
Cited by
79
References
62
Citations by year
2026: 3 · 2025: 3 · 2024: 4 · 2023: 5 · 2022: 3 · 2021: 5 · 2020: 3 · 2019: 6 · 2018: 19 · 2017: 4 · 2016: 4 · 2015: 4 · 2014: 8 · 2013: 6 · 2012: 1
FWCI
3.75
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Neuropsychopharmacology (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Alliance for Research on Schizophrenia and Depression (MH62185, MH48514, MH076049)
  • National Institute of Mental Health (MH 62185, MH48514, K23MH076049, R01MH048514, MH076049, P50MH062185)
Topics
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
  • Social Sciences › Psychology › Clinical Psychology › Suicide and Self-Harm Studies
  • Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
Keywords
major depressive disorder, suicidal ideation, suicidal behavior, paroxetine, bupropion, serotonin reuptake inhibitors, suicide attempt history, antidepressant efficacy, depression severity
MeSH terms
Adolescent, Adult, Affect, Aged, Major Depressive Disorder, Double-Blind Method, Female, Humans, Male, Middle Aged, Pilot Projects, Suicide, Bupropion, Treatment Outcome, Selective Serotonin Reuptake Inhibitors, Paroxetine, Dopamine Uptake Inhibitors, Suicidal Ideation

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