The DOI matches its Crossref record; 41 of the 42 references it cites were found in a registry or an index, and 1 are not checked yet.
Antidepressants and the Placebo Effect
Open accessAbstract
Antidepressants are supposed to work by fixing a chemical imbalance, specifically, a lack of serotonin in the brain. Indeed, their supposed effectiveness is the primary evidence for the chemical imbalance theory. But analyses of the published data and the unpublished data that were hidden by drug companies reveals that most (if not all) of the benefits are due to the placebo effect. Some antidepressants increase serotonin levels, some decrease it, and some have no effect at all on serotonin. Nevertheless, they all show the same therapeutic benefit. Even the small statistical difference between antidepressants and placebos may be an enhanced placebo effect, due to the fact that most patients and doctors in clinical trials successfully break blind. The serotonin theory is as close as any theory in the history of science to having been proved wrong. Instead of curing depression, popular antidepressants may induce a biological vulnerability making people more likely to become depressed in the future.
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“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 Kirsch, 2014
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“but, since an active placebo was not used, this could be related to the “breaking of the blind effect” (Kirsch, 2014).”
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 Kirsch, 2014
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Rush, A. J., Trivedi, M. H., Wisniewski, S. R., Nierenberg, A. A., Stewart, J. W., Warden, D., Niederehe, G., Thase, M. E., Lavori, P. W., Lebowitz, B. D., et al. (2006) · American Journal of Psychiatry · doi:10.1176/ajp.2006.163.11.1905 · Cited by 5,643
The American Journal of Psychiatry
(2011) · American Journal of Psychiatry · doi:10.1176/appi.ajp · Cited by 2,616
Kirsch, I., Deacon, B. J., Huedo-Medina, T. B., Scoboria, A., Moore, T. J., & Johnson, B. T. (2008) · PLoS Medicine · doi:10.1371/journal.pmed.0050045 · Cited by 2,442
Self-citationSelective publication of antidepressant trials and its influence on apparent efficacy
Turner, E. H., Matthews, A. M., Linardatos, E., Tell, R. A., & Rosenthal, R. (2008) · New England Journal of Medicine · doi:10.1056/nejmsa065779 · Cited by 2,435
Antidepressant Drug Effects and Depression Severity: A Patient-Level Meta-analysis
Fournier, J. C., DeRubeis, R. J., Hollon, S. D., Dimidjian, S., Amsterdam, J. D., Shelton, R. C., & Fawcett, J. (2010) · JAMA · doi:10.1001/jama.2009.1943 · Cited by 2,009
Exercise Treatment for Major Depression: Maintenance of Therapeutic Benefit at 10 Months
Babyak, M., Blumenthal, J. A., Herman, S., Khatri, P., Doraiswamy, M., Moore, K., Edward Craighead, W., Baldewicz, T. T., & Ranga Krishnan, K. (2000) · Psychosomatic Medicine · doi:10.1097/00006842-200009000-00006 · Cited by 1,063
Placebos without Deception: A Randomized Controlled Trial in Irritable Bowel Syndrome
Kaptchuk, T. J., Friedlander, E., Kelley, J. M., Sanchez, M. N., Kokkotou, E., Singer, J. P., Kowalczykowski, M., Miller, F. G., Kirsch, I., & Lembo, A. J. (2010) · PLoS ONE · doi:10.1371/journal.pone.0015591 · Cited by 900 · cited 2×
“My colleagues and I have tested and confirmed the hypothesis that placebos can be effective even when given openly, without deception, when given in the context of a warm therapeutic relationship and with an honest but convincing rationale as to why they should be effective (Kaptchuk et al., 2010).”
BackgroundResultSelf-citationPrevalence, burden, and treatment of insomnia in primary care
(1997) · American Journal of Psychiatry · doi:10.1176/ajp.154.10.1417 · Cited by 694 · cited 2×
“If that is the case, then the mere promise of an effective treatment should help to alleviate depression, by replacing hopelessness with hopefulness – the hope that one will recover after all.”
BackgroundMelander, H., Ahlqvist-Rastad, J., Meijer, G., & Beermann, B. (2003) · BMJ · doi:10.1136/bmj.326.7400.1171 · Cited by 634
Treatment-Emergent Sexual Dysfunction Related to Antidepressants: A Meta-Analysis
Serretti, A., & Chiesa, A. (2009) · Journal of Clinical Psychopharmacology · doi:10.1097/jcp.0b013e3181a5233f · Cited by 583
Research works printed but not linked: 6
- Beutler L. E., 1998, Prevention & Treatment, 1, 3c
- Fountoulakis K. N., 2011, International Journal of Neuro-Psychopharmacology, 14, 405
- Kirsch I., 1998, Prevention & Treatment, 1, 7r
- Klein D. F., 1998, Prevention & Treatment, 1, 6c
- Leber P., 1998, Memoradum to the Department of Health and Human Services, Public Health Service, Food and Drug Administration, Center for Drug Evaluation and Research
- NICE, 2004, Depression: Management of depression in primary and secondary care [Clinical practice guideline 23]
Cited by
Sorted by citations
More treatment but no less depression: The treatment-prevalence paradox
Ormel, J., Hollon, S. D., Kessler, R. C., Cuijpers, P., & Monroe, S. M. (2022) · Clinical Psychology Review · doi:10.1016/j.cpr.2021.102111 · Cited by 213
Kirmayer, L. J., Gómez-Carrillo, A., & Veissière, S. P. L. (2017) · Social Science & Medicine · doi:10.1016/j.socscimed.2017.04.034 · Cited by 156
Galvão-Coelho, N. L., Marx, W., Gonzalez, M., Sinclair, J., de Manincor, M., Perkins, D., & Sarris, J. (2021) · Psychopharmacology · doi:10.1007/s00213-020-05719-1 · Cited by 137
The role of lipid biomarkers in major depression
Parekh, A., Smeeth, D., Milner, Y., & Thuret, S. (2017) · Healthcare · doi:10.3390/healthcare5010005 · Cited by 120
Ormel (2019) · doi:10.1097/yco.0000000000000505 · Cited by 102
Metadata
- Authors
- Kirsch, I.
- Affiliations
- Beth Israel Deaconess Medical Center (US)
- Corresponding author
- Kirsch, Irving
- ORCID
- Kirsch, Irving
- Venue
- Zeitschrift für Psychologie
- Publisher
- Hogrefe Publishing Group
- Published
- 2014-01
- Volume
- 222
- Issue
- 3
- Pages
- 128-134
- ISSN
- 0044-3409 (ISSN-L)
- 2190-8370
- 2151-2604
- PMC
- PMC4172306
- OpenAlex
- W1974098282
- Cited by
- 164
- References
- 41
- Citations by year
- 2026: 4 · 2025: 12 · 2024: 13 · 2023: 16 · 2022: 18 · 2021: 20 · 2020: 11 · 2019: 16 · 2018: 16 · 2017: 21 · 2016: 10 · 2015: 5 · 2014: 2
- FWCI
- 7.07
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Zeitschrift für Psychologie (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Pain Management and Placebo Effect
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Social Sciences › Psychology › Clinical Psychology › Psychotherapy Techniques and Applications
- Keywords
- antidepressants, placebo effect, serotonin, chemical imbalance theory, depression, clinical trial data, publication bias, blinding, antidepressant efficacy, relapse
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