Treatment response for acute depression is not associated with number of previous episodes: Lack of evidence for a clinical staging model for major depressive disorder
Open accessAbstract
Mental illness has been observed to follow a neuroprogressive course, commencing with prodrome, then onset, recurrence and finally chronic illness. In bipolar disorder and schizophrenia responsiveness to treatment mirrors these stages of illness progression, with greater response to treatment in the earlier stages of illness and greater treatment resistance in chronic late stage illness. Using data from 5627 participants in 15 controlled trials of duloxetine, comparator arm (paroxetine, venlafaxine, escitalopram) or placebo for the treatment of an acute depressive episode, the relationship between treatment response and number of previous depressive episodes was determined. Data was dichotomised for comparisons between participants who had >3 previous episodes (n=1697) or ≤3 previous episodes (n=3930), and additionally for no previous episodes (n=1381) or at least one previous episode (n=4246). Analyses were conducted by study arm for each clinical trial, and results were then pooled. There was no significant difference between treatment response and number of previous depressive episodes. This unexpected finding suggests that treatments to reduce symptoms of depression during acute illness do not lose efficacy for patients with a longer history of illness.
Integrity signals
Registry
Cites
Statistics
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?
There are concerns that the natural course of bipolar and depressive disorders does not follow a clinical staging model.
“There are also concerns that the natural course of bipolar 220 and depressive 221 disorders does not follow a clinical staging model.”
From Preventive psychiatry: a blueprint for improving the mental health of young people (2021) · cites this paper as [221]
Cites
Development of a Rating Scale for Primary Depressive Illness
Hamilton, M. (1967) · British Journal of Social and Clinical Psychology · doi:10.1111/j.2044-8260.1967.tb00530.x · Cited by 8,410 · see citing works
Yatham, L. N., & Malhi, G. S. (2011) · Oxford University Press eBooks · doi:10.1093/med/9780199562305.001.0001 · Cited by 3,515 · see citing works
Maes, M., Galecki, P., Chang, Y. S., & Berk, M. (2011) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2010.05.004 · Cited by 1,140 · see citing works
Self-citationMcGorry, P. D., Hickie, I. B., Yung, A. R., Pantelis, C., & Jackson, H. J. (2006) · Australian & New Zealand Journal of Psychiatry · doi:10.1080/j.1440-1614.2006.01860.x · Cited by 919 · see citing works
Keller, M. B. (1992) · Archives of General Psychiatry · doi:10.1001/archpsyc.1992.01820100053010 · Cited by 864 · see citing works
Multiple recurrences of major depressive disorder
Solomon, D. A., Keller, M. B., Leon, A. C., Mueller, T. I., Lavori, P. W., Shea, M. T., Coryell, W., Warshaw, M., Turvey, C., Maser, J. D., et al. (2000) · American Journal of Psychiatry · doi:10.1176/appi.ajp.157.2.229 · Cited by 835 · see citing works
Kendler, K. S., Thornton, L. M., & Gardner, C. O. (2000) · American Journal of Psychiatry · doi:10.1176/appi.ajp.157.8.1243 · Cited by 721 · see citing works
Population-based study of first onset and chronicity in major depressive disorder
Eaton, W. W., Shao, H., Nestadt, G., Lee, B. H., Bienvenu, O. J., & Zandi, P. (2008) · Archives of General Psychiatry · doi:10.1001/archpsyc.65.5.513 · Cited by 612 · see citing works
Psychosocial Disability During the Long-term Course of Unipolar Major Depressive Disorder
Judd, L. L., Akiskal, H. S., Zeller, P. J., Paulus, M., Leon, A. C., Maser, J. D., Endicott, J., Coryell, W., Kunovac, J. L., Mueller, T. I., et al. (2000) · Archives of General Psychiatry · doi:10.1001/archpsyc.57.4.375 · Cited by 593 · see citing works
Moylan, S., Maes, M., Wray, N. R., & Berk, M. (2013) · Molecular Psychiatry · doi:10.1038/mp.2012.33 · Cited by 529 · see citing works
Self-citationSacher, J., Neumann, J., Fünfstück, T., Soliman, A., Villringer, A., & Schroeter, M. L. (2011) · Journal of Affective Disorders · doi:10.1016/j.jad.2011.08.001 · Cited by 410 · see citing works
Detke, M. J., Lu, Y., Goldstein, D. J., Hayes, J. R., & Demitrack, M. A. (2002) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.v63n0407 · Cited by 384 · see citing works
Duloxetine in the Treatment of Major Depressive Disorder: A Double-Blind Clinical Trial
Goldstein, D. J., Mallinckrodt, C., Lu, Y., & Demitrack, M. A. (2002) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.v63n0309 · Cited by 334 · see citing works
Goldstein, D. J., Lu, Y., Detke, M. J., Wiltse, C., Mallinckrodt, C., & Demitrack, M. A. (2004) · Journal of Clinical Psychopharmacology · doi:10.1097/01.jcp.0000132448.65972.d9 · Cited by 314 · see citing works
Detke, M. J., Wiltse, C. G., Mallinckrodt, C. H., McNamara, R. K., Demitrack, M. A., & Bitter, I. (2004) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2004.01.002 · Cited by 283 · see citing works
Duloxetine 60 mg once daily dosing versus placebo in the acute treatment of major depression
Detke, M. J., Lu, Y., GOLDSTEIN, D. J., McNamara, R. K., & Demitrack, M. A. (2002) · Journal of Psychiatric Research · doi:10.1016/s0022-3956(02)00060-2 · Cited by 278 · see citing works
McGorry, P. D., Nelson, B., Goldstone, S. D., & Yung, A. R. (2010) · The Canadian Journal of Psychiatry · doi:10.1177/070674371005500803 · Cited by 275 · see citing works
Setting the stage: from prodrome to treatment resistance in bipolar disorder
Berk, M., Conus, P., Lucas, N., Hallam, K. T., Malhi, G. S., Dodd, S., Yatham, L. N., Yung, A. R., & McGorry, P. D. (2007) · Bipolar Disorders · doi:10.1111/j.1399-5618.2007.00484.x · Cited by 239 · see citing works
Self-citationStaging of Mental Disorders: Systematic Review
Cosci, F., & Fava, G. A. (2013) · Psychotherapy and Psychosomatics · doi:10.1159/000342243 · Cited by 235 · see citing works
Moving towards a population health approach to the primary prevention of common mental disorders
Jacka, F. N., Mykletun, A., & Berk, M. (2012) · BMC Medicine · doi:10.1186/1741-7015-10-149 · Cited by 235 · see citing works
Self-citationRECOVERY, CHRONICITY, AND LEVELS OF PSYCHOPATHOLOGY IN MAJOR DEPRESSION
Mueller, T. I., & Leon, A. C. (1996) · Psychiatric Clinics of North America · doi:10.1016/s0193-953x(05)70275-6 · Cited by 234 · see citing works
Berk, M., Brnabic, A. J. M., Dodd, S., Kelin, K., Tohen, M. F., Malhi, G. S., Berk, L., Conus, P., & McGorry, P. D. (2011) · Bipolar Disorders · doi:10.1111/j.1399-5618.2011.00889.x · Cited by 187 · see citing works
Self-citationBrannan, S. K., Mallinckrodt, C. H., Brown, E. B., Wohlreich, M. M., Watkin, J. G., & Schatzberg, A. F. (2004) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2004.04.011 · Cited by 179 · see citing works
Advances in Protein Chemistry and Structural Biology
(2021) · Advances in protein chemistry and structural biology · doi:10.1016/s1876-1623(21)00003-1 · Cited by 174 · see citing works
KENNEDY, N., ABBOTT, R., & PAYKEL, E. S. (2003) · Psychological Medicine · doi:10.1017/s003329170300744x · Cited by 165 · see citing works
Progressive Brain Changes in Children and Adolescents With First-Episode Psychosis
Arango, C. (2012) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2011.150 · Cited by 147 · see citing works
Longitudinal Course of Bipolar I Disorder
Solomon, D. A., Leon, A. C., Coryell, W. H., Endicott, J., Li, C., Fiedorowicz, J. G., Boyken, L., & Keller, M. B. (2010) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2010.15 · Cited by 145 · see citing works
Asami, T., Sylvain Bouix, A., Whitford, T. J., Shenton, M. E., Salisbury, D. F., & McCarley, R. W. (2011) · NeuroImage · doi:10.1016/j.neuroimage.2011.08.066 · Cited by 143 · see citing works
Fichter, M. M., Quadflieg, N., Fischer, U. C., & Kohlboeck, G. (2009) · Acta Psychiatrica Scandinavica · doi:10.1111/j.1600-0447.2009.01512.x · Cited by 136 · see citing works
Nierenberg, A. A., Greist, J. H., Mallinckrodt, C. H., Prakash, A., Sambunaris, A., Tollefson, G. D., & Wohlreich, M. M. (2007) · Current Medical Research and Opinion · doi:10.1185/030079906x167453 · Cited by 131 · see citing works
Duloxetine in the treatment of major depressive disorder: a placebo- and paroxetine-controlled trial
David, P., Wang, F., Mallinckrodt, C. H., Walker, D. J., & Detke, M. J. (2006) · European Psychiatry · doi:10.1016/j.eurpsy.2006.03.004 · Cited by 128 · see citing works
ABCB1 polymorphism predicts escitalopram dose needed for remission in major depression
Singh, A., Bousman, C., Ng, C. H., Byron, K., & Berk, M. (2012) · Translational Psychiatry · doi:10.1038/tp.2012.115 · Cited by 110 · see citing works
Self-citationEarly life adversity is associated with brain changes in subjects at family risk for depression
Carballedo, A., Lisiecka, D., Fagan, A., Saleh, K., Ferguson, Y., Connolly, G., Meaney, J., & Frodl, T. (2012) · The World Journal of Biological Psychiatry · doi:10.3109/15622975.2012.661079 · Cited by 107 · see citing works
Progressive neurostructural changes in adolescent and adult patients with bipolar disorder
Lisy, M. E., Jarvis, K., DelBello, M. P., Mills, N. P., Weber, W. A., Fleck, D. E., Strakowski, S. M., & Adler, C. M. (2011) · Bipolar Disorders · doi:10.1111/j.1399-5618.2011.00927.x · Cited by 103 · see citing works
Magalhães, P. V. D. S., Dodd, S., Nierenberg, A. A., & Berk, M. (2012) · Australian & New Zealand Journal of Psychiatry · doi:10.1177/0004867412460593 · Cited by 98 · see citing works
Self-citationFrom neuroprogression to neuroprotection: implications for clinical care.
Berk, M., Conus, P., Kapczinski, F. P., Andreazza, A. C., Yücel, M., Wood, S. J., Pantelis, C., Malhi, G. S., Dodd, S., Bechdolf, A., et al. (2010) · PubMed · Cited by 96 · see citing works
Self-citationBasic symptoms in early psychotic and depressive disorders
Schultze‐Lutter, F., Ruhrmann, S., Picker, H., von Reventlow, H. G., Brockhaus‐Dumke, A., & Klosterkötter, J. (2007) · The British Journal of Psychiatry · doi:10.1192/bjp.191.51.s31 · Cited by 86 · see citing works
Eker, M. C., & Gönül, A. S. (2009) · The World Journal of Biological Psychiatry · doi:10.1080/15622970902737998 · Cited by 76 · see citing works
David, P., Pritchett, Y., Kajdasz, D. K., Bauer, M., Jain, R., Russell, J. M., Walker, D. J., Spencer, K. A., Froud, D. M., Raskin, J., et al. (2007) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2007.01.008 · Cited by 74 · see citing works
Pharmacogenetics of antidepressant response
Keers, R., & Aitchison, K. J. (2010) · Expert Review of Neurotherapeutics · doi:10.1586/ern.10.186 · Cited by 66 · see citing works
Wise, T. N., Wiltse, C. G., Iosifescu, D. V., Sheridan, M., Xu, J. Y., & Raskin, J. (2007) · International Journal of Clinical Practice · doi:10.1111/j.1742-1241.2007.01476.x · Cited by 62 · see citing works
Eker, M. C., & Gönül, A. S. (2010) · The World Journal of Biological Psychiatry · doi:10.3109/15622970902737998 · Cited by 59 · see citing works
Raskin, J., Wiltse, C. G., Dinkel, J. J., Walker, D. J., Desaiah, D., & Katona, C. (2008) · Journal of Clinical Psychopharmacology · doi:10.1097/jcp.0b013e318160738e · Cited by 58 · see citing works
Inflammation-Related Disorders in the Tryptophan Catabolite Pathway in Depression and Somatization
Anderson, G., Maes, M. H. J., & Berk, M. (2012) · Advances in protein chemistry and structural biology · doi:10.1016/b978-0-12-398314-5.00002-7 · Cited by 54 · see citing works
Self-citationLee, P., Shu, L., Xu, X., Wang, C., Lee, M. S., LIU, C., Hong, J. P., Ruschel, S. I., Raskin, J., Colman, S. A., et al. (2007) · Psychiatry and Clinical Neurosciences · doi:10.1111/j.1440-1819.2007.01666.x · Cited by 50 · see citing works
Parental Bonding and Self-Esteem as Predictors of Severe Depressive Symptoms
Grotmol, K. S., Ekeberg, Ø., Finset, A., Gude, T., Moum, T., Vaglum, P., & Tyssen, R. (2010) · The Journal of Nervous and Mental Disease · doi:10.1097/nmd.0b013e3181c8189c · Cited by 41 · see citing works
Oakes, T. M. M., Myers, A. L., Marangell, L. B., AHL, J. S. B., Prakash, A., Thase, M. E., & Kornstein, S. G. (2012) · Human Psychopharmacology Clinical and Experimental · doi:10.1002/hup.1262 · Cited by 36 · see citing works
Predictors of antidepressant response: A selective review
Dodd, S., & Berk, M. (2004) · International Journal of Psychiatry in Clinical Practice · doi:10.1080/13651500410005423 · Cited by 32 · see citing works
Self-citationMartinez, J. M., Katon, W. J., Greist, J. H., Kroenke, K., Thase, M. E., Meyers, A. L., Edwards, S. E., Marangell, L. B., Shoemaker, S., & Swindle, R. W. (2011) · International Clinical Psychopharmacology · doi:10.1097/yic.0b013e32834ce11b · Cited by 30 · see citing works
Raskin, J., Xu, J., & Kajdasz, D. (2008) · International Psychogeriatrics · doi:10.1017/s1041610207005649 · Cited by 28 · see citing works
David, P., Kajdasz, D. K., Royer, M. G., Walker, D. J., & Raskin, J. (2006) · International Clinical Psychopharmacology · doi:10.1097/00004850-200609000-00007 · Cited by 16 · see citing works
Rønning, J. A., Haavisto, A., Nikolakaros, G., Helenius, H. Y. M., Tamminen, T., Moilanen, I. K., Kumpulainen, K., Piha, J., Almqvist, F., & Sourander, A. (2010) · Social Psychiatry and Psychiatric Epidemiology · doi:10.1007/s00127-010-0182-6 · Cited by 14 · see citing works
Flagged first, then by citations
1 of the 53 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Preventive psychiatry: a blueprint for improving the mental health of young people
Fusar‐Poli, P., Correll, C. U., Arango, C., Berk, M., Patel, V., & Ioannidis, J. P. A. (2021) · World Psychiatry · doi:10.1002/wps.20869 · Cited by 497 · see citing works
Self-citationAnderson, G., Berk, M., Dean, O. M., Moylan, S., & Maes, M. H. J. (2013) · CNS Drugs · doi:10.1007/s40263-013-0119-1 · Cited by 93 · see citing works
Self-citationBerk, M., Mohebbi, M., Dean, O. M., Cotton, S., Chanen, A. M., Dodd, S., Ratheesh, A., Amminger, G. P., Phelan, M., Weller, A., et al. (2020) · BMC Medicine · doi:10.1186/s12916-019-1475-6 · Cited by 72 · see citing works
Self-citationPrevalence of ADHD symptoms across clinical stages of major depressive disorder
Bron, T. I., Bijlenga, D., Verduijn, J., Penninx, B. W. J. H., Beekman, A. T. F., & Kooij, J. J. S. (2016) · Journal of Affective Disorders · doi:10.1016/j.jad.2016.02.053 · Cited by 68 · see citing works
Saccaro, L. F., Tassone, M., Tozzi, F., & Rutigliano, G. (2024) · Journal of Affective Disorders · doi:10.1016/j.jad.2024.03.150 · Cited by 42 · see citing works
Marshe, V. S., Islam, F., Maciukiewicz, M., Bousman, C., Eyre, H. A., Lavretsky, H., Mulsant, B. H., Reynolds, C. F., Lenze, E. J., & Müller, D. J. (2020) · American Journal of Geriatric Psychiatry · doi:10.1016/j.jagp.2020.01.007 · Cited by 39 · see citing works
Between wellness, relapse, and remission: Stages of illness in anorexia nervosa
Steinglass, J. E., Glasofer, D. R., Dalack, M., & Attia, E. (2020) · International Journal of Eating Disorders · doi:10.1002/eat.23237 · Cited by 28 · see citing works
Montgomery, S., Gommoll, C., Chen, C., & Greenberg, W. M. (2014) · CNS Spectrums · doi:10.1017/s1092852914000273 · Cited by 27 · see citing works
Clarke, S. L., Soons, N., Videler, A. C., van Alphen, S. P. J., Van, H. L., Dil, L., Pappijn, L., Corbeij, S., Broekhof, B., Chanen, A. M., et al. (2025) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2024.1473051 · Cited by 16 · see citing works
The clinical relevance of qualitatively distinct subtypes of depression
Kessing, L. V., & Bukh, J. D. (2017) · World Psychiatry · doi:10.1002/wps.20461 · Cited by 12 · see citing works
Altın, M., Harada, E., Schacht, A., Berggren, L., Walker, D. J., & Dueñas, H. (2014) · Open Journal of Depression · doi:10.4236/ojd.2014.33015 · Cited by 8 · see citing works
Self-citationStaging of depressive disorders: Relevance of resistance to treatment and residual symptoms
Reneses, B., Aguera-Ortiz, L., Sevilla-Llewellyn-Jones, J., Carrillo, A., Argudo, I., Regatero, M. J., López-Micó, C., Fuentes, M., & Palomo, T. (2020) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2020.07.022 · Cited by 7 · see citing works
Kornstein, S. G., Gommoll, C., Chen, C., & Kramer, K. L. (2015) · Journal of Affective Disorders · doi:10.1016/j.jad.2015.12.058 · Cited by 6 · see citing works
Schoemaker, J. H., Kilian, S., Emsley, R. A., & Vingerhoets, A. J. J. M. (2018) · Neurology Psychiatry and Brain Research · doi:10.1016/j.npbr.2018.04.002 · Cited by 3 · see citing works
Ossola, P., Gerra, M. L., Luviè, L., Piacente, A., Marchesi, C., Schoretsanitis, G., & Stewart, J. W. (2025) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2025.02.013 · Cited by 2 · see citing works
Barros, B. R., Schacht, A., Happich, M., Televantou, F., Berggren, L., Walker, D. J., & Dueñas, H. (2014) · The Primary Care Companion For CNS Disorders · doi:10.4088/pcc.14m01661 · Cited by 2 · see citing works
Self-citationClinical staging and profiling of affective disorders
Beekman, A. T. F., Kupka, R., & van Exel, E. R. (2026) · Neuropsychopharmacology · doi:10.1038/s41386-026-02325-1 · Cited by 1 · see citing works
Clinical staging in depression
de la Fuente-Tomás, L., & García‐Portilla, M. P. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-817933-8.00026-8
Clinical Staging of Psychiatric Disorders: Its Utility in Mental Health Prevention
Rutigliano, G., & Grande, C. D. (2022) · Springer eBooks · doi:10.1007/978-3-030-97906-5_2
- Authors
- Dodd, S., Berk, M., Kelin, K., Mancini, M., & Schacht, A.
- Affiliations
- Deakin University (AU)
- Mental Health Research Institute (AU)
- Eli Lilly (Australia) (AU)
- Eli Lilly (Italy) (IT)
- Eli Lilly (Germany) (DE)
- Corresponding author
- Dodd, Seetal
- Venue
- Journal of Affective Disorders
- Publisher
- Elsevier BV
- Published
- 2013-09
- Volume
- 150
- Issue
- 2
- Pages
- 344-349
- ISSN
- 0165-0327 (ISSN-L)
- OpenAlex
- W1986876872
- Cited by
- 20
- References
- 53
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1 · 2022: 1 · 2021: 2 · 2020: 4 · 2018: 2 · 2017: 1 · 2016: 1 · 2015: 1 · 2014: 3 · 2013: 1
- FWCI
- 1.46
- Type
- journal article
- Language
- en
- Open access
- green
- figshare.com
- Licence
- Locations
- Journal of Affective Disorders (publishedVersion)
- PubMed (publishedVersion)
- Figshare (submittedVersion, cc-by)
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Social Sciences › Psychology › Social Psychology › Mental Health Treatment and Access
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Keywords
- major depressive disorder, acute depression, treatment response, clinical staging model, neuroprogression, duloxetine, antidepressant efficacy, treatment resistance, chronic depression, disease history
- MeSH terms
- Duloxetine Hydrochloride, Venlafaxine Hydrochloride, Acute Disease, Adult, Antidepressive Agents, Cyclohexanols, Depression, Major Depressive Disorder, Female, Humans, Male, Middle Aged, Recurrence, Thiophenes, Time Factors, Citalopram, Treatment Outcome, Paroxetine
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