Hypothalamic-pituitary-adrenal (HPA) axis functioning as predictor of antidepressant response - meta-analysis
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Objective Although antidepressants are effective, around 50% of depressed patients are non-responsive. At the same time, some patients show alterations in the hypothalamic-pituitary-adrenal (HPA) axis. Due to interactions with central monoaminergic systems, these may profit less from antidepressants.Method To determine whether non-responders and responders differed in pre-treatment HPA axis functioning, the Cochrane Library, EMBASE, MEDLINE, and PsycINFO were searched. Studies using patients with depression being treated with antidepressants, and including both a pre-treatment HPA and a post-treatment response measure were included. Standardised mean differences were calculated for meta-analysis.Results Thirty-nine studies were included. Non-responders and responders did not differ in pre-treatment corticotropin-releasing hormone or adrenocorticotropic hormone. Meta-regression showed non-responders had comparably higher pre-treatment cortisol in studies measuring cortisol non-invasively, not reporting sample storage, failing to control for age, and excluding patients with comorbidities.Conclusions Only studies with a specific methodological profile seem to be able to show that the more marked depressed patients' alterations in the HPA axis, the less likely they are to profit from antidepressants.
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Pharmacological treatment can modulate cortisol levels independently of promoting remission of depressive symptoms.
“Previous studies have shown that pharmacological treatment can modulate cortisol levels independently of promoting remission of depressive symptoms. [8][9]][10]”
From Can physical exercise modulate cortisol level in subjects with depression? A systematic review and meta-analysis (2018) · cites this paper as [10]
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Kwok, W. Y., Wagner-Schuman, M. L., Eisenlohr-Moul, T. A., & Hage, B. (2025) · Journal of Personalized Medicine · doi:10.3390/jpm15120607 · Cited by 1 · see citing works
Depressive Störungen in der Adoleszenz: Aktuelle Studienlage zur Mikrobiota-Darm-Hirn-Achse
Kandsperger, S., Brunner, R. M., Rupprecht, R., & Baghai, T. C. (2023) · Zeitschrift für Kinder- und Jugendpsychiatrie und Psychotherapie · doi:10.1024/1422-4917/a000917 · Cited by 1 · see citing works
Depressive and Anxiety Disorders
Tonini, E., Hickie, I. B., & Crouse, J. J. (2024) · Elsevier eBooks · doi:10.1016/b978-0-323-99967-0.00189-7 · Cited by 1 · see citing works
Kavita, K., Tiwari, R. K., Joshi, U., & Sahu, M. K. (2021) · International Journal of Current Research and Review · doi:10.31782/ijcrr.2021.132017
High rates of mood disorders in patients with chronic idiopathic eosinopenia
Magen, E., Geishin, A., Weizman, A., Merzon, E., Green, I., Magen, I., Yakov, A., Manor, I., Ashkenazi, S., Vinker, S., et al. (2024) · Brain Behavior & Immunity - Health · doi:10.1016/j.bbih.2024.100847
Interplay Between Serotonin Transporter and Glucocorticoid Receptor on Anxiety and Depression
Padovan, C. M., Tirapelli, C. R., Campos‐Cardoso, R., & Souza, C. D. D. M. (2024) · Springer eBooks · doi:10.1007/978-3-031-32035-4_19-1
More, H. H., Singh, A. D., & Ghildiyal, A. (2025) · International Journal of Research in Medical Sciences · doi:10.18203/2320-6012.ijrms20250685
Überblick über psychosoziale Kerndomänen bei der Behandlung und Erforschung von Post-COVID
Salzmann, S., Rief, W., & EURONET-SOMA-Gruppe (2025) · Verhaltenstherapie · doi:10.1159/000547743
Interplay Between Serotonin Transporter and Glucocorticoid Receptor on Anxiety and Depression
Padovan, C. M., Tirapelli, C. R., Campos‐Cardoso, R., & Souza, C. D. D. M. (2025) · Springer eBooks · doi:10.1007/978-3-031-73368-0_19
Jonassen, R., Øverli, Ø., Hilland, E., Nilsen, H. L., Esbensen, Q. Y., Lirussi, L., Heiberg, H., Rønning, K. H., Gorissen, M. E. E., Kraft, B., et al. (2026) · Comprehensive Psychoneuroendocrinology · doi:10.1016/j.cpnec.2026.100363
- Authors
- Fischer, S., Macare, C., & Cleare, A. J.
- Affiliations
- King's College London (GB)
- Corresponding author
- Fischer, Susanne
- Venue
- Neuroscience & Biobehavioral Reviews
- Publisher
- Elsevier BV
- Published
- 2017-12
- Volume
- 83
- Pages
- 200-211
- ISSN
- 0149-7634 (ISSN-L)
- OpenAlex
- W2763620392
- Cited by
- 70
- References
- 36
- Citations by year
- 2026: 1 · 2025: 8 · 2024: 8 · 2023: 9 · 2022: 8 · 2021: 8 · 2020: 8 · 2019: 12 · 2018: 8
- FWCI
- 0.67
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (am, 324 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Neuroscience & Biobehavioral Reviews (acceptedVersion)
- PubMed (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion)
- Research Portal (King's College London) (submittedVersion, cc-by-nc-nd)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion)
- Zurich Open Repository and Archive (University of Zurich)
- Funders
- National Institutes of Health Research
- Medical Research Council
- Wellcome Trust
- Royal Society
- Swiss National Science Foundation
- National Institute for Health Research
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Keywords
- hypothalamic-pituitary-adrenal axis, antidepressant response, depression, treatment-resistant depression, cortisol, corticotropin-releasing factor, ACTH, pretreatment biomarkers, monoaminergic systems, methodological quality
- MeSH terms
- Animals, Antidepressive Agents, Humans, Hypothalamo-Hypophyseal System, Pituitary-Adrenal System
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