The DOI matches its Crossref record; 20 of the 21 references it cites were found in a registry or an index.
Severity of Depression and Response to Antidepressants and Placebo: An Analysis of the Food and Drug Administration Database
Abstract
Some studies suggest that more severely ill patients with depression respond well to antidepressants and poorly to placebo, whereas those who are mildly ill respond equally well to antidepressants and placebo. This notion has implications for the design of clinical trials. To further assess and substantiate these putative predictors of antidepressant and placebo response, we assessed the Food and Drug Administration database of 45 phase II and III antidepressant clinical trials. The frequency of statistically significant differences between antidepressants and placebo was higher in the trials that included patients with more severe depression. In the antidepressant-treated groups, the magnitude of symptom reduction was significantly related to mean initial Hamilton Rating Scale for Depression (HAM-D) score; the higher the mean initial HAM-D score, the larger the change. With placebo treatment, however, the higher the mean initial HAM-D score, the smaller the change. Early discontinuation was more frequent among patients whose mean initial HAM-D scores were higher. These data may help inform the design of future antidepressant clinical trials.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
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
“Individual-level meta-analyses have found a direct relationship between the magnitude of depressive symptoms and the effectiveness of antidepressants.8–10”
Citations
Cites
Hamilton, M. (1960) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp.23.1.56 · Cited by 32,817
Elkin, I. (1989) · Archives of General Psychiatry · doi:10.1001/archpsyc.1989.01810110013002 · Cited by 2,300
Khan, A., Warner, H. A., & Brown, W. A. (2000) · Archives of General Psychiatry · doi:10.1001/archpsyc.57.4.311 · Cited by 475
Self-citationPrediction of Tricyclic Antidepressant Response
Bielski, R. J. (1976) · Archives of General Psychiatry · doi:10.1001/archpsyc.1976.01770120083009 · Cited by 349
Predictors of Drug Response in Depression
Joyce, P. R. (1989) · Archives of General Psychiatry · doi:10.1001/archpsyc.1989.01810010091014 · Cited by 279
Clinical pharmacology of imipramine and related antidepressant compounds.
KLERMAN, G. L., & Jo, C. (1967) · PubMed · Cited by 273
Which depressions respond to placebo?
Fairchild, C., Rush, A. J., Vasavada, N., Giles, D. E., & Khatami, M. (1986) · Psychiatry Research · doi:10.1016/0165-1781(86)90109-5 · Cited by 106
Clinical features of depressed patients who do and do not improve with placebo
Brown, W. A., Johnson, M. F. K., & Chen, M.-G. (1992) · Psychiatry Research · doi:10.1016/0165-1781(92)90002-k · Cited by 102
Self-citationNeurophysiologic predictors of treatment response to fluoxetine in major depression
Cook, I. A., Leuchter, A. F., Witte, E. A., Abrams, M., Uijtdehaage, S. H. J., Stubbeman, W. F., Rosenberg-Thompson, S., & Anderson‐Hanley, C. (1999) · Psychiatry Research · doi:10.1016/s0165-1781(99)00010-4 · Cited by 70
Predictors of placebo response: a retrospective analysis.
Wilcox, C. S., Cohn, J. B., Rd, L., Heiser, J. F., Lucas, P. B., Morgan, D. L., & Defrancisco, D. F. (1992) · PubMed · Cited by 59
Research works printed but not linked: 6
- Klerman, 1965, Pharmacol Rev, 17, 101
- Morris, 1974, Arch Gen Psychiatry, 31, 33
- Brown, 1988, Psychopharmacol Bull, 24, 14
- Galinowski, 1991, Encephale, 17, 387
- Peselow, 1989, Br J Psychiatry, 155, 667
- Wilcox, 1992, Psychopharmacol Bull, 28, 157
Cited by
Sorted by citations
Items 401–456 of 456
Kokkoli, E. (2013) · Electronic Theses of LMU Munich (Ludwig-Maximilians-Universität München) · doi:10.5282/edoc.16664
St John's wort as treatment for depression.
Oppel, L. (2002) · PubMed Central
Ethical and Deontological Issues in Psychiatry
Chiriţă, A. L. (2014) · American Journal of Psychiatry and Neuroscience · doi:10.11648/j.ajpn.20140206.13
Thase, M. E., Larsen, K. G., & Kennedy, S. H. (2011)
Pharmacokinetics of Antidepressants and Lithium
Mathematisch-naturwissenschaftlichen Fakultät, I. (2003)
The “Ignored Common Factor”: The Role of Expectancy in the Treatment of Adolescent Depression
Murakami, J. L. (2011) · Scholars' Bank (University of Oregon)
O’Mullan, C. (2015) · eSpace (Curtin University)
Gyllenhaal, C. (2002) · Integrative Cancer Therapies · doi:10.1177/153473540200100416
Metaanalysen in der Therapieevaluation
Kösters, M. (2010) · OPen Access Repositorium der Universität Ulm (OPARU) (Ulm University) · doi:10.18725/oparu-2104
Karazsia, B. T., & Schultz, M. M. (2016) · Ecopsychology · doi:10.1089/eco.2015.0078
Psychopharmacology of mood disorders
Coryell, W. H., & Geddes, J. R. (2008) · Cambridge University Press eBooks · doi:10.1017/cbo9780511544392.029
Prinzipien der Methodik empirischer Forschung in der Psychiatrie
Möller, H., & Broich, K. (2017) · Springer eBooks · doi:10.1007/978-3-662-49295-6_18
Emotion and cognition in Parkinson’s disease
Moonen, A. J. H. (2016) · doi:10.26481/dis.20160324am
Pasterkiewicz, U. B. (2017) · UWSpace (University of Waterloo)
The Effectiveness of Antidepressants Today
Giraldi, T. (2017) · Springer eBooks · doi:10.1007/978-3-319-57657-2_8
Selection and measurement of control antidepressants in clinical tests for Chinese
Liu, H., Yang, Z., Geng, Y., Yang, H., De-heng, Z., Xiao, W.-D., & Wang, G. (2017) · Medicine · doi:10.1097/md.0000000000008327
The issue of indiscriminative efficacy trials and placebo effects in paediatric psychopharmacology
Siegfried, K. (2019) · Elsevier eBooks · doi:10.1016/b978-0-08-100616-0.00009-5
How do we determine whether antidepressants are useful or not? – Authors' reply
Hieronymus, F., Lisinski, A., Nilsson, S., & Eriksson, E. (2019) · The Lancet Psychiatry · doi:10.1016/s2215-0366(19)30383-9
Two steps forward, one step back
Krepel, N. (2021) · Research Publications (Maastricht University) · doi:10.26481/dis.20210618nk
From the Second Half of the Twentieth Century to the Early Twenty-First: The Psychopharmacologic Era
Fountoulakis, K. (2021) · Psychiatry · doi:10.1007/978-3-030-86541-2_11 · Cited by 1
Holbrook, A. M., Goldsmith, C. H., & Leung, M. (2005) · Encyclopedia of Biostatistics · doi:10.1002/0470011815.b2a04037
Laux, G. (2016) · Springer eBooks · doi:10.1007/978-3-642-45028-0_67-1
(2002) · Human Psychopharmacology Clinical and Experimental · doi:10.1002/hup.359
Laux, G. (2011) · Springer eBooks · doi:10.1007/978-3-642-03637-8_55
Blasini, M., Corsi, N., & Colloca, L. (2018) · Springer eBooks · doi:10.1007/978-3-319-95369-4_17
Miscellaneous conditions and substances
(2005) · CRC Press eBooks · doi:10.1201/b14455-9
Holbrook, A. M., Goldsmith, C. H., & Leung, M. (2008) · Wiley Encyclopedia of Clinical Trials · doi:10.1002/9780471462422.eoct984
Holbrook, A. M., Goldsmith, C. H., & Leung, M. (2014) · doi:10.1002/9781118596005.ch61
Buckley, P., Prewette, D., Bird, J., & Harrison, G. (2004) · CRC Press eBooks · doi:10.1201/b13311-22
Laux, G. (2008) · Springer eBooks · doi:10.1007/978-3-540-33129-2_55
Prinzipien der Methodik empirischer Forschung in der Psychiatrie
Möller, H., & Broich, K. (2015) · Springer eBooks · doi:10.1007/978-3-642-45028-0_18-1
Holtzheimer, P. E. (2012) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.717960225.793463302
Holbrook, A. M., Goldsmith, C. H., & Leung, M. (2005) · Encyclopedia of Statistical Sciences · doi:10.1002/0471667196.ess7191
The serotonin theory of depression: how the media got it all wrong
(2022) · Pharmaceutical journal/The pharmaceutical journal · doi:10.1211/pj.2022.1.153955
Oppel, L. (2003) · PubMed Central
Damm, J. (2023) · PsyArXiv (OSF Preprints) · doi:10.31234/osf.io/xya7r
Predicting non-response to ketamine for depression: a symptom-level analysis of real-world dataPreprint
Miller, E. A., Afshar, H. T., Mishra, J., & Ramanathan, D. (2023) · medRxiv · doi:10.1101/2023.07.03.23292094
Societal well-being is reflected in outcomes of antidepressant clinical trials.Preprint
Lebedev, A. V., Acar, K., Osika, W., Simonsson, O., Kringelbach, M. L., Deco, G., Ingvar, M., & Petrović, P. (2023) · Research Square · doi:10.21203/rs.3.rs-3408330/v1
Antidepressant Medication and Psychotherapy: Why It Matters
Chiesa, M. (2024) · British Journal of Psychotherapy · doi:10.1111/bjp.12938
Damm, J. (2025) · PsyArXiv (OSF Preprints) · doi:10.31234/osf.io/xya7r_v2
Damm, J. (2025) · Current Psychology · doi:10.1007/s12144-025-08842-4 · Cited by 1
Walter, K. H., Otis, N. P., Ray, T. N., Glassman, L. H., Beltran, J. L., Kobayashi Elliott, K. T., & Michalewicz-Kragh, B. (2024) · Figshare · doi:10.6084/m9.figshare.26569516
Seifert, J., Bleich, S., & Seifert, R. (2026) · Springer eBooks · doi:10.1007/978-3-662-72738-6_22
Piksa, M., Cieslik-Starkiewicz, A., & Ryguła, R. (2026) · Psychopharmacology · doi:10.1007/s00213-026-07060-5
Sunzeri, F. (2026) · Springer eBooks · doi:10.1007/978-3-032-14465-2_16
Siedel, J. A. (2005) · Revista de Psicoterapia · doi:10.33898/rdp.v16i61.942
(2014) · Europe PMC (PubMed Central) · Cited by 24
Metadata
- Authors
- Khan, A., Leventhal, R. M., Khan, S. R., & Brown, W. A.
- Affiliations
- Northwest Clinical Research Center (US)
- Tufts University (US)
- Corresponding author
- Khan, Arif
- Leventhal, Robyn M.
- Khan, Shirin R.
- Venue
- Journal of Clinical Psychopharmacology
- Published
- 2002-02
- Volume
- 22
- Issue
- 1
- Pages
- 40-45
- ISSN
- 0271-0749 (ISSN-L)
- OpenAlex
- W2094608167
- Cited by
- 456
- References
- 21
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 6 · 2023: 13 · 2022: 13 · 2021: 10 · 2020: 14 · 2019: 28 · 2018: 18 · 2017: 21 · 2016: 18 · 2015: 33 · 2014: 41 · 2013: 20 · 2012: 27
- FWCI
- 10.78
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Clinical Psychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Life Sciences › Neuroscience › Cognitive Neuroscience › Pain Management and Placebo Effect
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Keywords
- depression severity, antidepressant response, placebo response, antidepressant clinical trials, trial design, Hamilton Depression Rating Scale, treatment discontinuation, symptom relief
- MeSH terms
- Adolescent, Adult, Antidepressive Agents, Depressive Disorder, Double-Blind Method, Humans, Personality Inventory, United States, United States Food and Drug Administration, Placebo Effect, Randomized Controlled Trials as Topic, Databases, Factual, Treatment Outcome, Clinical Trials, Phase II as Topic, Clinical Trials, Phase III as Topic
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.
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 ›
Are you an author, or do you see a problem with this page? Request a review
