Biological markers evaluated in randomized trials of psychological treatments for depression: a systematic review and meta-analysis
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Abstract
Though it is widely believed that psychotherapy changes biology, this contention is largely based on observational data, subject to confounding. We report the first systematic review and meta-analysis of biological variables assessed, as outcomes or predictors of response, in randomized controlled trials of psychotherapy for adult depression. Fifty-one trials (5123 participants) and a pooled analysis were included. Biological markers were outcomes in 43 studies and predictors of treatment response in 9. At post-treatment, psychotherapy could not be distinguished from control conditions for glycaemic control (Hb1AC), 7 trials, Hedges' g= -.01, 95% CI -0.30 to 0.29, I 2 = 65% and cortisol concentration after-wake, 5 trials, Hedges' g= -.19, 95% CI -0.45 to 0.06, I 2 = 0%. Follow-up results were similar. For the other biological domains (immunological, neurobiological, inflammatory, weight, blood pressure), overall findings were mixed and often inconsistent. Few trials investigated prediction of response, with only neuroimaging markers showing promise. Across domains, we found limited evidence that benefits of psychological treatments for depression translate to biological outcomes.
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Reviews have found no evidence to support dose escalation but some evidence for the other strategies (switching, augmentation).
“Reviews have found no evidence to support dose escalation but some evidence for the other strategies.”
From Time for united action on depression: a Lancet–World Psychiatric Association Commission (2022) · cites this paper as [534]
Recent systematic reviews of pharmacotherapy studies identified seven trials for dose escalation, four for switching of antidepressants, 48 for various augmentation agents, or 25 studies for augmentation of pharmacotherapy with psychotherapies.
“Recent systematic reviews of pharmacotherapy studies identified seven trials for dose escalation, 534 four for switching of antidepressants, 535 48 for various augmentation agents, or 25 studies for augmentation of pharmacotherapy with psychotherapies. 536”
From Time for united action on depression: a Lancet–World Psychiatric Association Commission (2022) · cites this paper as [534]
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- Authors
- Cristea, I. A., Karyotaki, E., Hollon, S. D., Cuijpers, P., & Gentili, C.
- Affiliations
- Babeș-Bolyai University (RO)
- Amsterdam Public Health (NL)
- Vanderbilt University (US)
- University of Padua (IT)
- Corresponding author
- Gentili, Claudio
- Venue
- Neuroscience & Biobehavioral Reviews
- Publisher
- Elsevier BV
- Published
- 2019-06
- Volume
- 101
- Pages
- 32-44
- ISSN
- 0149-7634 (ISSN-L)
- OpenAlex
- W2930641302
- Cited by
- 34
- References
- 95
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 3 · 2023: 6 · 2022: 5 · 2021: 6 · 2020: 10
- FWCI
- 0.83
- Type
- journal article
- Language
- en
- Update notices
- erratum (2019-09-01)
- Open access
- bronze
- doi.org
- Locations
- Neuroscience & Biobehavioral Reviews (publishedVersion)
- PubMed (publishedVersion)
- VU Research Portal (acceptedVersion, other-oa)
- OSF Preprints (OSF Preprints) (submittedVersion)
- OSF Preprints (OSF Preprints) (submittedVersion, cc-by)
- Padua Research Archive (University of Padova) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Funders
- Romanian Ministery of Research and Innovation, CNCS – UEFISCDI (PN-III-P1-1.1-TE-2016-1054)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Psychotherapy Techniques and Applications
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Keywords
- depression, psychotherapy, biomarkers, treatment response prediction, glycemic control, HbA1c, cortisol, neuroimaging, immunological markers, inflammatory markers, blood pressure, weight
- MeSH terms
- Brain, Depression, Depressive Disorder, Glycated Hemoglobin, Humans, Hydrocortisone, Psychotherapy, Biomarkers, Randomized Controlled Trials as Topic, Treatment Outcome, Neuroimaging
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.
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