The DOI matches its Crossref record, with a small difference in title or year; 54 of the 56 references it cites were found in a registry or an index.
Antidepressant Drug Effects and Depression Severity: A Patient-Level Meta-analysis
Open accessAbstract
CONTEXT: Antidepressant medications represent the best established treatment for major depressive disorder, but there is little evidence that they have a specific pharmacological effect relative to pill placebo for patients with less severe depression. OBJECTIVE: To estimate the relative benefit of medication vs placebo across a wide range of initial symptom severity in patients diagnosed with depression. DATA SOURCES: PubMed, PsycINFO, and the Cochrane Library databases were searched from January 1980 through March 2009, along with references from meta-analyses and reviews. STUDY SELECTION: Randomized placebo-controlled trials of antidepressants approved by the Food and Drug Administration in the treatment of major or minor depressive disorder were selected. Studies were included if their authors provided the requisite original data, they comprised adult outpatients, they included a medication vs placebo comparison for at least 6 weeks, they did not exclude patients on the basis of a placebo washout period, and they used the Hamilton Depression Rating Scale (HDRS). Data from 6 studies (718 patients) were included. DATA EXTRACTION: Individual patient-level data were obtained from study authors. RESULTS: Medication vs placebo differences varied substantially as a function of baseline severity. Among patients with HDRS scores below 23, Cohen d effect sizes for the difference between medication and placebo were estimated to be less than 0.20 (a standard definition of a small effect). Estimates of the magnitude of the superiority of medication over placebo increased with increases in baseline depression severity and crossed the threshold defined by the National Institute for Clinical Excellence for a clinically significant difference at a baseline HDRS score of 25. CONCLUSIONS: The magnitude of benefit of antidepressant medication compared with placebo increases with severity of depression symptoms and may be minimal or nonexistent, on average, in patients with mild or moderate symptoms. For patients with very severe depression, the benefit of medications over placebo is substantial.
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“antidepressants have been demonstrated efficient in treating MDD”
From SSRI Treatment Response Prediction in Depression Based on Brain Activation by Emotional Stimuli (2020) · cites this paper as [1]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Fournier and colleagues meta-analysed trials of selective serotonin reuptake inhibitors and estimated the effect size.45 For mild to severe depression the effect estimates ranged from -0.17 to -0.11; this is lower than the effect size for smoking cessation.”
From Change in mental health after smoking cessation: systematic review and meta-analysis (2014) · cites this paper as [45]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“For SSRIs, researchers have argued that a substantial portion of the perceived therapeutic benefit in double-blind randomized clinical trials (RCTs) may stem from placebo responses rather than the drug itself (Sugarman et al., 2014; Fournier et al., 2010; Kirsch, 2014; Moncrieff and Kirsch, 2015).”
From Revisiting the SSRI vs. placebo debate in the treatment of social anxiety disorder: the role of expectancy effects, neural responsivity, and monoamine transporters (2025) · cites this paper as Fournier et al., 2010
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The introduction and widespread use of selective serotonine uptake inhibitors (SSRI) [22, 23] and psychological therapy including cognitive behavioral therapy (CBT) [24, 25] meant that well tolerated and effective treatments for depression and anxiety disorders became available in primary care, widening the group of individuals eligible for treatment.”
From Trends in psychiatric diagnoses, medications and psychological therapies in a large Swedish region: A population-based study (2020) · cites this paper as [23]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“there are differences in individual response”
From SSRI Treatment Response Prediction in Depression Based on Brain Activation by Emotional Stimuli (2020) · cites this paper as [1]
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In the citing paper
“In addition, the effect sizes are generally higher than those obtained for pharmacological treatment of mild-to-moderate depression [34]”
From One-Day Acceptance and Commitment Therapy Compared to Support for Depressed Migraine Patients: a Randomized Clinical Trial. (2020) · cites this paper as [34]
In the citing paper
“Two individual participant data meta-analysis (26, 27) indicated that patients with lower baseline severity would achieve smaller improvement compared to placebo.”
In the citing paper
“Individual-level meta-analyses have found a direct relationship between the magnitude of depressive symptoms and the effectiveness of antidepressants.8–10”
In the citing paper
“Thus, the benefits of antidepressants in non-severe depression have been argued to be minimal.8 11”
In the citing paper
“One small individual patient data meta-analysis found support for increasing benefit with increasing severity of depression,20 but three larger individual patient data meta-analyses did not find any such effect of antidepressants compared with placebo on depression severity .44–46”
From Should antidepressants be used for major depressive disorder? (2020) · cites this paper as [20]
In the citing paper
“For example, meta-analysis has demonstrated that antidepressants, though widely prescribed as a treatment for MDD, may be no more effective than placebo for mild to moderate levels of symptom severity; clinically significant benefits are only observed at “very severe” levels of impairment (18).”
From Depression in diabetes: have we been missing something important? (2011) · cites this paper as [18]
In the citing paper
“For example, meta-analysis has demonstrated that antidepressants, though widely prescribed as a treatment for MDD, may be no more effective than placebo for mild to moderate levels of symptom severity; clinically significant benefits are only observed at “very severe” levels of impairment (18).”
From Depression in diabetes: have we been missing something important? (2011) · cites this paper as [18]
In the citing paper
“Although antidepressants are unlikely to be effective in most presentations of distress (18), physical activity, psychotherapeutic approaches, and discussions with diabetes team members can be effective.”
From Depression in diabetes: have we been missing something important? (2011) · cites this paper as [18]
In the citing paper
“The strength of the pooled standardised mean difference in change was clinically important - the association between smoking cessation and change in depression and anxiety was equal to or larger than the estimate from trials of antidepressants versus placebo.”
From An application of the stress-diathesis model: A review about the association between smoking tobacco, smoking cessation, and mental health (2023) · cites this paper as Fournier et al., 2010
In the citing paper
“A meta-analysis of individual-level data from randomised controlled trials (RCTs) of antidepressants for”
From An application of the stress-diathesis model: A review about the association between smoking tobacco, smoking cessation, and mental health (2023) · cites this paper as Fournier et al., 2010
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Metadata
- Authors
- Fournier, J. C., DeRubeis, R. J., Hollon, S. D., Dimidjian, S., Amsterdam, J. D., Shelton, R. C., & Fawcett, J.
- Affiliations
- University of Pennsylvania (US)
- University of New Mexico (US)
- Venue
- JAMA
- Publisher
- American Medical Association (AMA)
- Published
- 2010-01-06
- Volume
- 303
- Issue
- 1
- Pages
- 47
- ISSN
- 0002-9955 (ISSN-L)
- 0098-7484
- PMC
- PMC3712503
- OpenAlex
- W2004762037
- Cited by
- 2,009
- References
- 56
- Citations by year
- 2026: 54 · 2025: 72 · 2024: 89 · 2023: 70 · 2022: 81 · 2021: 134 · 2020: 81 · 2019: 111 · 2018: 143 · 2017: 128 · 2016: 112 · 2015: 149 · 2014: 154 · 2013: 170 · 2012: 172
- FWCI
- 144.95
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- JAMA (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Bristol-Myers Squibb
- Eli Lilly and Company
- Pfizer
- GlaxoSmithKline
- Sanofi
- National Alliance for Research on Schizophrenia and Depression
- Universiteit Maastricht
- National Institute of Mental Health (K24MH001741, R10 MH50129, R01MH060998, K02MH001697, R10MH055875, R10MH055877)
- Janssen Pharmaceuticals
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Health Sciences › Medicine › Psychiatry and Mental health › Mental Health Treatment and Access
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Keywords
- antidepressants, major depressive disorder, depression severity, placebo response, Hamilton Depression Rating Scale, treatment effect heterogeneity, mild depression, antidepressant efficacy
- MeSH terms
- Adult, Antidepressive Agents, Depression, Major Depressive Disorder, Humans, Placebo Effect, Randomized Controlled Trials as Topic, Treatment Outcome
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