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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 But analyses of the published data and the unpublished data that were hidden by drug companies reveals that most (if not all) of the benefits are due to the placebo effect.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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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
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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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