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Cited by 311Treatment of Major DepressionMental Health Treatment and AccessAnxiety, Depression, Psychometrics, Treatment, Cognitive Processes

Are Antidepressant Drugs That Combine Serotonergic and Noradrenergic Mechanisms of Action More Effective Than the Selective Serotonin Reuptake Inhibitors in Treating Major Depressive Disorder? A Meta-analysis of Studies of Newer Agents

Papakostas, George I., Thase, Michael E., Fava, Maurizio, Nelson, J. Craig, Shelton, Richard C.·2007·Biological Psychiatry
DOI 10.1016/j.biopsych.2007.03.027
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Abstract

Background Recent studies suggest that the treatment of major depressive disorder (MDD) with newer antidepressant drugs that simultaneously enhance norepinephrine and serotonin neurotransmission might result in higher response and remission rates than the selective serotonin reuptake inhibitors (SSRIs). The goal of our work was to compare response rates among patients with MDD treated with either of these two broad categories of antidepressant drugs. Methods Medline/Pubmed, EMBase, clinical trial registries, program syllabi from major psychiatric meetings held since 1995, and documents from relevant pharmaceutical companies were searched for double-blind, randomized trials comparing a newer serotonergic-noradrenergic antidepressant drug (venlafaxine, duloxetine, milnacipran, mirtazapine, mianserin, or moclobemide) with an SSRI for MDD. Results Ninety-three trials (n = 17,036) were combined using a random-effects model. Treatment with serotonergic + noradrenergic antidepressant drugs was more likely to result in clinical response than the SSRIs (risk ratio [RR] = 1.059; response rates 63.6% versus 59.3%; p = .003). There was no evidence for heterogeneity among studies combined (p = 1.0). Excluding each individual agent did not significantly alter the pooled RR. With the exception of duloxetine (.985), RRs for response for each individual serotonergic + noradrenergic antidepressant drug were within the 95% confidence interval of the pooled RR (1.019-1.101). Conclusions Serotonergic-noradrenergic antidepressant drugs seem to have a modest efficacy advantage compared with SSRIs in MDD. With the Number Needed to Treat (NNT) statistic as one indicator of clinical significance, nearly 24 patients would need to be treated with dual-action antidepressant drugs instead of SSRIs in order to obtain one additional responder. This difference falls well below the mark of NNT = 10 suggested by the United Kingdom's National Institute of Clinical Excellence but nonetheless might be of public health relevance given the large number of depressed patients treated with SSRI /serotonin-norepinephrine reuptake inhibitor (SNRI) antidepressant drugs. Further research is needed to examine whether larger differences between classes of antidepressant drugs might exist in specific MDD sub-populations or for specific MDD symptoms.

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  • A patient prescribed an SSRI who continues to manifest debilitating anhedonia, fatigue, and psychomotor retardation may exhibit significant improvement when switching to an antidepressant with a different mechanism of action.

    “For example, a patient prescribed an SSRI who continues to manifest debilitating anhedonia, fatigue, and psychomotor retardation may exhibit significant improvement when switching to an antidepressant with a different mechanism of action 181,182 .”

    From Treatment‐resistant depression: definition, prevalence, detection, management, and investigational interventions (2023) · cites this paper as [181]

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Authors
Papakostas, G. I., Thase, M. E., Fava, M., Nelson, J. C., & Shelton, R. C.
Affiliations
  • Harvard University (US)
  • University of Pittsburgh Medical Center (US)
  • University of California, San Francisco (US)
  • Vanderbilt University (US)
Corresponding author
Papakostas, George I.
ORCID
Venue
Biological Psychiatry
Publisher
Elsevier BV
Published
2007-12
Volume
62
Issue
11
Pages
1217-1227
ISSN
0006-3223 (ISSN-L)
DOI
10.1016/j.biopsych.2007.03.027
OpenAlex
W1996039326
Cited by
308
References
137
Citations by year
2026: 3 · 2025: 5 · 2024: 11 · 2023: 6 · 2022: 11 · 2021: 5 · 2020: 4 · 2019: 13 · 2018: 6 · 2017: 17 · 2016: 13 · 2015: 23 · 2014: 14 · 2013: 31 · 2012: 24
FWCI
3.32
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Biological Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute of Mental Health (K23MH069629)
Topics
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
  • Social Sciences › Psychology › Social Psychology › Mental Health Treatment and Access
  • Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
Keywords
major depressive disorder, selective serotonin reuptake inhibitors, venlafaxine, duloxetine, milnacipran, mirtazapine, mianserin, moclobemide, antidepressant efficacy, treatment response, remission, number needed to treat, norepinephrine uptake
MeSH terms
Antidepressive Agents, Data Interpretation, Statistical, Depressive Disorder, Major, Major Depressive Disorder, Humans, Norepinephrine, Randomized Controlled Trials as Topic, Selective Serotonin Reuptake Inhibitors, Adrenergic Uptake Inhibitors

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