The DOI matches its Crossref record; 68 of the 68 references it cites were found in a registry or an index; 7 of the 96 sources its claims cite were checked for support.
Should antidepressants be used for major depressive disorder?
Open accessAbstract
Background: Major depressive disorder is estimated by the WHO to affect more than 300 million people globally, making depression the leading cause of disability worldwide. Antidepressants are commonly used to treat depression. Objective: The study aimed to provide an update on the evidence on the effects of antidepressants compared with placebo. Should antidepressants be used for adults with major depressive disorder? Study selection: We searched the Cochrane Library, BMJ Best Practice and PubMed up to June 2019 with the search terms ‘depression’ and ‘antidepressants’ targeting reviews published in English since 1990. Findings: Several reviews have assessed the effects of antidepressants compared with placebo for depression. Generally, all the previous reviews show that antidepressants seem to have statistically significant effects on depressive symptoms, but the size of the effect has questionable importance to most patients. Antidepressants seem to have minimal beneficial effects on depressive symptoms and increase the risk of both serious and non-serious adverse events. Conclusions: The benefits of antidepressants seem to be minimal and possibly without any importance to the average patient with major depressive disorder. Antidepressants should not be used for adults with major depressive disorder before valid evidence has shown that the potential beneficial effects outweigh the harmful effects.
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Written from the paper’s full text.
TL;DR
This narrative review argues that antidepressants for adults with major depressive disorder produce statistically significant but clinically minimal symptom reductions and increase adverse events, so benefits may not outweigh harms. The authors conclude antidepressants should not be used for major depressive disorder until valid evidence shows net benefit.
Key findings
- Across reviews, antidepressants versus placebo show statistically significant effects on depressive symptoms, but effect sizes are below clinical significance thresholds. In the authors’ 2017 systematic review, SSRIs versus placebo reduced HDRS by 1.94 points (95% CI −2.50 to −1.37) or SMD −0.23 (95% CI −0.31 to −0.14), below NICE’s 3-point/0.5 SMD threshold and far from a 7-point HDRS/0.875 SMD “minimal improvement.”
- A large network meta-analysis found overall antidepressants versus placebo SMD 0.30 (95% credibility interval 0.26 to 0.34), which the authors call presumably without clinical relevance; only 18% of included trials were assessed at low risk of bias.
- SSRIs significantly increased the risk of both serious and non-serious adverse events; common long-term adverse effects include gastrointestinal problems, sleep disturbances, and sexual dysfunction, and withdrawal symptoms can persist more than 2 weeks and sometimes several months. Longer-term effects (SMD 0.34) and NICE results (SMD 0.28) seemed as small as short-term effects.
- Industry involvement and bias were prominent: industry-sponsored studies more often showed benefits (RR 1.27, 95% CI 1.17 to 1.37) and favorable conclusions (RR 1.34, 95% CI 1.19 to 1.51), and meta-analyses with a manufacturer-employed author were 22-fold less likely to have negative statements. In STAR*D, 77.8% of patients would have been excluded from conventional trials, with HDRS improvement of 6.6 points after 3 months of SSRI treatment versus 14.8 points in conventional comparator trials.
Methods
- Narrative review: two investigators independently searched the Cochrane Library, BMJ Best Practice, and PubMed up to June 2019 for English reviews published since 1990 using the terms “depression” and “antidepressants”; they included any review assessing benefits and harms of any antidepressant versus placebo in adults, plus references and relevant guideline recommendations.
- No protocol was published before the literature search. The synthesis is narrative rather than systematic, and it focuses on adults with a primary diagnosis of major depressive disorder, excluding primary somatic disorders or other disorders.
- Main analysis is a narrative synthesis of identified reviews, with attention to clinical significance thresholds, risk of bias, industry involvement, and harms.
Limitations
- Stated: no protocol was published before the literature search; the majority of previous antidepressant trials were at high or unclear risk of bias; evidence has low generalisability because trials include highly selected patients; short-term trials likely underestimate adverse effects; the HDRS is psychometrically and conceptually flawed; and no studies clearly identify who will respond to antidepressants.
- Stated: the authors’ GRADE assessment of the certainty of evidence was very low certainty.
- Evident: as a narrative review without a protocol or systematic meta-analysis, selection and interpretation of included reviews may be susceptible to bias, and the paper relies on existing reviews rather than new primary data.
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Claims the paper makes
65 Not checked yet · 17 Own interpretation · 6 No basis given · 5 Own method · 2 Supported · 2 Partly supported · accuracy not yet measured
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The above-mentioned systematic review assessing the effects of SSRIs (see ‘How good are antidepressants?’ section) also concluded that the vast majority of the included trials (39 out of 43 trials) with useful data were at high risk of ‘for profit’ bias.”
§ Should antidepressants be used for major depressive disorder? > Industry involvement in research and the possible implications
What the sources say
- Partly supportedcites [28] Jakobsen, 2017, Selective serotonin reuptake inhibitors versus placebo in patients with major depressive disorder. A systematic review with meta-analysis and trial sequential analysis, BMC Psychiatr sourceExperimental — accuracy not yet measured
The Results (Primary outcomes; page unavailable) compare trials at low versus high risk of financial bias and say that four trials were at low risk. The retrieved passages do not establish that 43 trials had useful data or that 39 of them were at high risk of ‘for profit’ bias, so the specific count is unsupported. (LLM, conf=0.78)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Thus, unemployment increases the risk of experiencing conditions that contribute to and perpetuate psychological distress, such as relative poverty, financial stress, loss of personal control and autonomy, and poor social support.61”
§ Should antidepressants be used for major depressive disorder? > Other treatment options?
What the sources say
- Supportedcites [61] Crowe, 2016, The role of financial hardship, mastery and social support in the association between employment status and depression: results from an Australian longitudinal cohort study, BMJ Open source
The Conclusion states that, compared with employment, unemployment increases the risk of the listed conditions, which contribute to and perpetuate psychological distress. The citing sentence closely paraphrases that passage. (LLM, conf=0.95)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
In the paper
“Generally, all the previous reviews show that antidepressants seem to have statistically significant effects on depressive symptoms”
§ Should antidepressants be used for major depressive disorder? > Abstract > Findings
What the sources say
- Not checked yetcites [30] source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Moreover, we have not identified any studies that identify clearly who will respond to antidepressants and who will not.”
§ Should antidepressants be used for major depressive disorder? > How much difference should antidepressants make?
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
In the paper
“The few trials assessing long-term effects showed that such effects seemed even smaller than the short-term effects.”
§ Should antidepressants be used for major depressive disorder? > How good are antidepressants?
What the sources say
- Not checked yetcites [28] Jakobsen, 2017, Selective serotonin reuptake inhibitors versus placebo in patients with major depressive disorder. A systematic review with meta-analysis and trial sequential analysis, BMC Psychiatr source
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“All these previous reviews show that antidepressants have statistically significant effects on depressive symptoms.”
§ Should antidepressants be used for major depressive disorder? > How good are antidepressants?
What the sources say
- Not checked yetcites [30] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“That review found, as all other previous reviews have shown, that SSRIs compared with placebo had a statistically significant effect on depressive symptoms.”
§ Should antidepressants be used for major depressive disorder? > How good are antidepressants?
What the sources say
- Not checked yetcites [28] Jakobsen, 2017, Selective serotonin reuptake inhibitors versus placebo in patients with major depressive disorder. A systematic review with meta-analysis and trial sequential analysis, BMC Psychiatr source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“The effect size of SSRIs (1.94 HDRS points, 95% CI −2.50 to −1.37; or −0.23 SMD, 95% CI −0.31 to −0.14)”
§ Should antidepressants be used for major depressive disorder? > How good are antidepressants?
What the sources say
- Not checked yetcites [28] Jakobsen, 2017, Selective serotonin reuptake inhibitors versus placebo in patients with major depressive disorder. A systematic review with meta-analysis and trial sequential analysis, BMC Psychiatr source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“There were almost no data on suicidal behaviour or quality of life.”
§ Should antidepressants be used for major depressive disorder? > How good are antidepressants?
What the sources say
- Not checked yetcites [28] Jakobsen, 2017, Selective serotonin reuptake inhibitors versus placebo in patients with major depressive disorder. A systematic review with meta-analysis and trial sequential analysis, BMC Psychiatr source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Results from a large trial conducted in a clinical setting (the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial) showed that 77.8% of the patients in the STAR*D trial would have been excluded in conventional clinical trials.”
§ Should antidepressants be used for major depressive disorder? > Limitations of current evidence for antidepressants
What the sources say
- Not checked yetcites [42] source
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- It may state two separate claims as one. 33
- Probably not a substantial claim. 13
Every source the paper cites for this claim was checked and supports it.
In the paper
“was, however, below the predefined threshold for clinical significance (the above-mentioned NICE criteria) and far from ‘minimal improvement’ (eg, seven-point change on the HDRS or an SMD of 0.875).”
§ Should antidepressants be used for major depressive disorder? > How good are antidepressants?
What the sources say
- Supportedcites [28] Jakobsen, 2017, Selective serotonin reuptake inhibitors versus placebo in patients with major depressive disorder. A systematic review with meta-analysis and trial sequential analysis, BMC Psychiatr source
The Results report an average SSRI–placebo difference of 2.25 HDRS points across 92 trials. The Discussion sets the predefined NICE-based threshold at 3 points or an SMD of 0.50, and cites 7 points or an SMD of 0.875 as corresponding to ‘minimal improvement.’ It explicitly concludes that the average effect did not meet its threshold for clinical significance. (LLM, conf=0.94)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Trials at high or unclear risk of bias tend to overestimate benefits and underestimate harms.”
§ Should antidepressants be used for major depressive disorder? > Limitations of current evidence for antidepressants
What the sources say
- Not checked yetcites [30] source
- Not checked yetcites [32] source
- Partly supportedcites [33] sourceExperimental — accuracy not yet measured
The Results report that trials at high or unclear risk of bias for sequence generation, allocation concealment, or blinding exaggerated intervention effects on average; the Methods say outcomes were coded so that lower odds ratios represented benefit. The paper does not separately establish that such trials underestimate harms, and the Results found little evidence of exaggerated effects for incomplete outcome data. Page numbers were not available in our copy. (LLM, conf=0.88)
- Not checked yetcites [34] source
- Partly supportedcites [36] sourceExperimental — accuracy not yet measured
The Discussion (page not available in our copy) reports that lack of patient blinding exaggerated effect sizes for patient-reported outcomes in complementary/alternative medicine trials. This supports the overestimated-benefits part in that specific setting, but the paper does not establish the claim for trials at high or unclear risk of bias generally or report that harms were underestimated. (LLM, conf=0.88)
- Not checked yetcites [37] Hróbjartsson, 2012, Observer bias in randomised clinical trials with binary outcomes: systematic review of trials with both blinded and non-blinded outcome assessors, BMJ source
- Partly supportedcites [38] sourceExperimental — accuracy not yet measured
The Abstract (page unavailable) reports that nonblinded assessors produced more beneficial treatment-effect estimates than blinded assessors in trials with subjective measurement-scale outcomes. The Limitations section (page unavailable) confines the findings to similar trials. The paper does not establish the broader claim about all trials at high or unclear risk of bias, or address underestimation of harms. (LLM, conf=0.90)
- Could not verifycites [39] Lundh A , Lexchin J , Mintzes B , et al . Industry sponsorship and research outcome. Cochrane Database Syst Rev 2017;2.doi:10.1002/14651858.MR000033.pub3 sourceExperimental — accuracy not yet measured
The review’s ‘Risk of bias: industry sponsored versus non-industry sponsored studies’ section compares trial bias by sponsorship, not whether high- or unclear-risk trials overestimate benefits or underestimate harms. Its ‘Reasons for favorable outcomes’ section discusses favorable efficacy results and under-reporting of harms, but does not establish the claimed relationship with trial risk of bias. Searched for overestimated benefits, underestimated harms, and high or unclear trial risk of bias; the indexed passages provide no direct assessment of that claim. (LLM, conf=0.73)
- Not checked yetcites [40] Nüesch E , Trelle S , Reichenbach S , et al . The effects of excluding patients from the analysis in randomised controlled trials: meta-epidemiological study. BMJ 2009;339.doi:10.1136/bmj.b3244 source
- Not checked yetcites [41] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“We found that SSRIs significantly increased the risk of both serious and non-serious adverse events.”
§ Should antidepressants be used for major depressive disorder? > How good are antidepressants?
What the sources say
- Not checked yetcites [28] Jakobsen, 2017, Selective serotonin reuptake inhibitors versus placebo in patients with major depressive disorder. A systematic review with meta-analysis and trial sequential analysis, BMC Psychiatr source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The vast majority of the previous reviews were non-systematic reviews (according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)), that is, narrative reviews.”
§ Should antidepressants be used for major depressive disorder? > How good are antidepressants?
What the sources say
- Not checked yetcites [31] Liberati, 2009, The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration, BMJ source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“As mentioned, several other reviews have been published generally confirming that antidepressants have statistically significant effects, but only a few of these reviews assessed the clinical significance of the review results.”
§ Should antidepressants be used for major depressive disorder? > How good are antidepressants?
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds. It may state two separate claims as one.
In the paper
“That review found no significant effect of SSRIs on the HDRS in trials at low risk of ‘for profit’ bias, whereas the beneficial effects were statistically significant in trials at high or unclear risk of ‘for profit’ bias.”
§ Should antidepressants be used for major depressive disorder? > Industry involvement in research and the possible implications
What the sources say
- Not checked yetcites [28] Jakobsen, 2017, Selective serotonin reuptake inhibitors versus placebo in patients with major depressive disorder. A systematic review with meta-analysis and trial sequential analysis, BMC Psychiatr source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the 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”
§ Should antidepressants be used for major depressive disorder? > Whom to treat?
What the sources say
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Other studies have found support for increasing benefit with increasing severity of depression,21 but the effects size even for patients with the most severe depression was still minimal.21”
§ Should antidepressants be used for major depressive disorder? > Whom to treat?
What the sources say
- Not checked yetcites [21] Kirsch, 2008, Initial severity and antidepressant benefits: a meta-analysis of data submitted to the food and drug administration, PLoS Med source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“NICE previously suggested that a three-point difference on the HDRS or a 0.5 standardised mean difference (SMD) met the criteria for clinical significance (minimally important difference).”
§ Should antidepressants be used for major depressive disorder? > How much difference should antidepressants make?
What the sources say
- Not checked yetcites [19] National Institute for Clinical Excellence . Depression: management of depression. primary and secondary care clinical practice guideline no 23 London: NICE, 2004. Available: wwwniceorguk/pageaspx?o=235213
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Furthermore, a person who improves by ≥50% is called a responder, whereas one who improves by 49% is called a non-responder, thus inflating the apparent difference between these patients.”
§ Should antidepressants be used for major depressive disorder? > How much difference should antidepressants make?
What the sources say
- Not checked yetcites [26] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The diagnosis of major depressive disorder in clinical practice is based on the presence of certain symptoms according to the diagnostic criteria outlined in either the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) or the International Classification of Diseases-10th Revision.”
§ Should antidepressants be used for major depressive disorder? > How is major depressive disorder diagnosed?
What the sources say
- Not checked yetcites [4] WHO . The ICD-10 classification of mental and behavioral disorders: clinical descriptions and diagnostic guidelines. Available: http://www.who.int/classifications/icd/en/bluebook.pdf [Accessed Mar 2018].
- Not checked yetcites [5] American Psychiatric Association . Practice guideline for the treatment of patients with major depressive disorder. 3rd edn, 2010.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“The above-mentioned thresholds suggested by NICE were not empirically based and are presumably too small.”
§ Should antidepressants be used for major depressive disorder? > How much difference should antidepressants make?
What the sources say
- Not checked yetcites [23] source
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“all available evidence shows that a difference of, for example, two HDRS points must be regarded as a minimal effect and is presumably undetectable by the average patient with depression.”
§ Should antidepressants be used for major depressive disorder? > How much difference should antidepressants make?
What the sources say
- Not checked yetcites [23] source
boosted- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“It must also be noted that when other assessment scales are used (eg, Beck Depression Inventory, Montgomery-Åsberg Depression Rating Scale, Hamilton six-item scale), the results correspond to the HDRS results, that is, statistically significant results with questionable importance to the average patient.”
§ Should antidepressants be used for major depressive disorder? > How much difference should antidepressants make?
What the sources say
- Not checked yetcites [28] Jakobsen, 2017, Selective serotonin reuptake inhibitors versus placebo in patients with major depressive disorder. A systematic review with meta-analysis and trial sequential analysis, BMC Psychiatr source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“so there is a great risk that the results of the review overestimate the beneficial effects and underestimate the harmful effects of SSRIs.”
§ Should antidepressants be used for major depressive disorder? > How good are antidepressants?
What the sources say
boostedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“We have not published a protocol before performing the literature search, which is a limitation.”
§ Should antidepressants be used for major depressive disorder? > Introduction
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Neither serious nor non-serious adverse events were assessed in the network meta-analysis.”
§ Should antidepressants be used for major depressive disorder? > How good are antidepressants?
What the sources say
- Not checked yetcites [35] Cipriani, 2018, Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis, The Lancet source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“It should, however, be noted that these empirically derived thresholds do not necessarily provide a precise estimate of what patients consider the smallest worthwhile effect of antidepressants.”
§ Should antidepressants be used for major depressive disorder? > How much difference should antidepressants make?
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The benefits of antidepressants seem to be minimal and possibly without any importance to the average patient with major depressive disorder.”
§ Should antidepressants be used for major depressive disorder? > Abstract > Conclusions
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Hence, when assessing such dichotomised outcomes, there is a considerable risk of overestimating benefit, but there is also a risk of not detecting a ‘true’ effect.”
§ Should antidepressants be used for major depressive disorder? > How much difference should antidepressants make?
plainconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Conversely, a person who improves by ≥50% is categorised as being the same as a person whose symptoms disappear completely, and one with 49% improvement is considered the same as a person showing no improvement at all.”
§ Should antidepressants be used for major depressive disorder? > How much difference should antidepressants make?
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Consequently, it may be argued that it is not even possible to assess the clinical relevance of a given HDRS score, and that the evidence base is thus fundamentally flawed due to the reliance on the HDRS.”
§ Should antidepressants be used for major depressive disorder? > How much difference should antidepressants make?
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Even if the trials used matching placebo, due to easily recognised adverse events in the experimental group and lack of adverse effect in the control groups, some patients might be able to figure out if they received an antidepressant or a placebo, which might compromise blinding and hence valid assessment of subjective symptoms.”
§ Should antidepressants be used for major depressive disorder? > Limitations of current evidence for antidepressants
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“As a substantial proportion of research concerning antidepressants is prone to ‘for profit bias’, the results of previous results likely overestimate benefit and underestimate harm.”
§ Should antidepressants be used for major depressive disorder? > Industry involvement in research and the possible implications
What the sources say
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Even though there is no valid evidence showing beneficial effects of antidepressants for depression, we cannot exclude that the evidence is showing beneficial effects for other conditions than major depressive disorder.”
§ Should antidepressants be used for major depressive disorder? > How good are antidepressants?
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds. It may state two separate claims as one.
In the paper
“Industry-sponsored studies showed more often benefits, relative risk (RR) 1.27 (95% CI 1.17 to 1.37), and more often favourable conclusions, RR 1.34 (95% CI 1.19 to 1.51).”
§ Should antidepressants be used for major depressive disorder? > Industry involvement in research and the possible implications
What the sources say
- Not checked yetcites [39] Lundh A , Lexchin J , Mintzes B , et al . Industry sponsorship and research outcome. Cochrane Database Syst Rev 2017;2.doi:10.1002/14651858.MR000033.pub3 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Despite biases inflating beneficial effects of review results, they still show only negligible differences between antidepressants and placebo on depressive symptoms, and the ‘true’ effect of antidepressants might not even be statistically significant.”
§ Should antidepressants be used for major depressive disorder? > Limitations of current evidence for antidepressants
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“so there is a great risk that the results of the review overestimate the beneficial effects and underestimate the harmful effects of antidepressants.”
§ Should antidepressants be used for major depressive disorder? > How good are antidepressants?
What the sources say
boostedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Nevertheless, if the effect estimates from the previous reviews are related to, for example, the NICE criteria (see ‘How much difference should antidepressants make?’ section), then the previous reviews confirm that antidepressants generally have minimal beneficial effects on depressive symptoms.”
§ Should antidepressants be used for major depressive disorder? > How good are antidepressants?
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Such an effect size is presumably without any clinical relevance.”
§ Should antidepressants be used for major depressive disorder? > How good are antidepressants?
What the sources say
- Not checked yetcites [24] Moncrieff, 2015, Empirically derived criteria cast doubt on the clinical significance of antidepressant-placebo differences, Cont Clin Trials source
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These data indicate that, in a clinical setting, the benefit of antidepressants is low and that the exclusion criteria typically used in randomised clinical trials lead to inflated effect estimates.”
§ Should antidepressants be used for major depressive disorder? > Limitations of current evidence for antidepressants
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“A non-systematic review showed that adding antidepressants to psychotherapy seemed to have a statistically significant effect, but again the effect was minimal and below the NICE criteria (SMD 0.35; 95% CI 0.24 to 0.45; p<0.001).10”
§ Should antidepressants be used for major depressive disorder? > Combination of antidepressants and psychotherapy
What the sources say
- Not checked yetcites [10] source
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The effects of adding antidepressants to psychotherapy seem negligible just as the effects of antidepressants when used as the only therapy.”
§ Should antidepressants be used for major depressive disorder? > Combination of antidepressants and psychotherapy
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Even though the increased relative risk of a serious adverse event is quite large, the absolute risk of a serious adverse event is still small, while SSRI adverse events not considered severe are more common.”
§ Should antidepressants be used for major depressive disorder? > What are the harms?
What the sources say
- Not checked yetcites [28] Jakobsen, 2017, Selective serotonin reuptake inhibitors versus placebo in patients with major depressive disorder. A systematic review with meta-analysis and trial sequential analysis, BMC Psychiatr source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“A non-systematic review showed that adding antidepressants to psychotherapy seemed to have a statistically significant effect, but again the effect was minimal and below the NICE criteria (SMD 0.35; 95% CI 0.24 to 0.45; p<0.001).10”
§ Should antidepressants be used for major depressive disorder? > Combination of antidepressants and psychotherapy
What the sources say
- Not checked yetcites [10] source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
In the paper
“It has been shown that SSRIs, the most commonly used antidepressants, increase the risk of both serious and non-serious adverse events.28”
§ Should antidepressants be used for major depressive disorder? > What are the harms?
What the sources say
- Not checked yetcites [28] Jakobsen, 2017, Selective serotonin reuptake inhibitors versus placebo in patients with major depressive disorder. A systematic review with meta-analysis and trial sequential analysis, BMC Psychiatr source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Withdrawal symptoms might also explain why some studies have alleged to show that the risk of relapse seems to be reduced if antidepressants are continued instead of not continued.54 55”
- Also stated in: § Withdrawal symptoms · hedged
“Withdrawal symptoms might be the reason why patients who do not continue antidepressants might do worse compared with patients who continue antidepressants.”
§ Should antidepressants be used for major depressive disorder? > Withdrawal symptoms
What the sources say
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Also stated in: § Withdrawal symptoms · hedged
In the paper
“Withdrawal symptoms after SSRIs typically occur within a few days from drug discontinuation and last a few weeks, also with gradual tapering”
§ Should antidepressants be used for major depressive disorder? > Withdrawal symptoms
What the sources say
- Not checked yetcites [52] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Non-randomised studies have, for example, shown that TCAs can cause seizures as well as death due to the slowing of intraventricular conduction, leading to complete heart block or ventricular arrhythmias.49”
§ Should antidepressants be used for major depressive disorder? > What are the harms?
What the sources say
- Not checked yetcites [49] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Antidepressants in combination with psychotherapy are recommended for major depressive disorder by both NICE and the American Psychiatric Association, as well as other guidelines.5 13 14 16 56 57”
§ Should antidepressants be used for major depressive disorder? > Combination of antidepressants and psychotherapy
What the sources say
- Not checked yetcites [5] American Psychiatric Association . Practice guideline for the treatment of patients with major depressive disorder. 3rd edn, 2010.
- Not checked yetcites [13] source
- Not checked yetcites [14] Gelenberg AJ , Freeman MP , Markowitz JC , et al . Practice guideline for the treatment of patients with major depressive disorder. 3rd edn. American Psychiatric Association, 2010.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“International guidelines, as a first step, recommend sleep hygiene institution and implementing lifestyle changes, such as adopting regular exercise,14 16 smoking cessation and a healthy diet,14 16 tapering of drugs that can lower mood, and addressing substance use if relevant16”
§ Should antidepressants be used for major depressive disorder? > Other treatment options?
What the sources say
- Not checked yetcites [14] Gelenberg AJ , Freeman MP , Markowitz JC , et al . Practice guideline for the treatment of patients with major depressive disorder. 3rd edn. American Psychiatric Association, 2010.
- Not checked yetcites [16] source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
The paper relies on this without support.
The DSM-5 and ICD-10 diagnostic criteria for major depressive disorder are largely comparable.
“These two sets of diagnostic criteria are largely comparable.”
The paper relies on this without support.
There are no objective tests or laboratory tests for depression or for validating the diagnosis.
“There are no objective tests and no laboratory test (eg, blood tests, MRI scans) for depression or for validating the diagnosis.”
The paper relies on this without support.
The HDRS is the most commonly used depression rating scale and is recommended by psychiatrists worldwide.
“The HDRS is the most commonly used depression rating scale and is the recommended scale by psychiatrists worldwide.”
The paper relies on this without support.
Theoretically and in clinical practice, some patients might benefit significantly from antidepressants.
“theoretically and in clinical practice some patients might benefit significantly from antidepressants.”
The paper relies on this without support.
Adverse effects of other types of antidepressant than SSRIs are not thoroughly assessed in systematic reviews.
“Adverse effects of other types of antidepressant than SSRIs (eg, serotonin-norepinephrine reuptake inhibitors and tricyclic antidepressants (TCAs)) are not thoroughly assessed in systematic reviews”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Thus, the benefits of antidepressants in non-severe depression have been argued to be minimal.8 11”
Citations
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“61 While such determinants”
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Metadata
- Authors
- Jakobsen, J. C., Gluud, C., & Kirsch, I.
- Affiliations
- University of Southern Denmark (DK)
- Copenhagen University Hospital (DK)
- Harvard University (US)
- Corresponding author
- Jakobsen, Janus Christian
- Venue
- BMJ Evidence-Based Medicine
- Publisher
- BMJ
- Published
- 2019-09-25
- Volume
- 25
- Issue
- 4
- Pages
- 130-130
- ISSN
- 1356-5524 (ISSN-L)
- 2515-446X
- 2515-4478
- PMC
- PMC7418603
- OpenAlex
- W2976089272
- Semantic Scholar
- c4a6ec1e247c44823d725a842af2cf3753519d60
- Cited by
- 162
- References
- 67
- Citations by year
- 2026: 13 · 2025: 28 · 2024: 21 · 2023: 38 · 2022: 22 · 2021: 24 · 2020: 14 · 2019: 2
- FWCI
- 1.99
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- BMJ Evidence-Based Medicine (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- University of Southern Denmark Research Portal (University of Southern Denmark) (submittedVersion, cc-by-nc)
- 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 › Clinical Psychology › Psychological Treatments and Disorders
- Keywords
- antidepressants, major depressive disorder, depression, antidepressant efficacy, antidepressant side effects, placebo comparison, risk-benefit assessment, treatment decision-making
- MeSH terms
- Antidepressive Agents, Depressive Disorder, Major, Major Depressive Disorder, Humans, Treatment Outcome
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-09, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-09 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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