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Cross-trial prediction of treatment outcome in depression: a machine learning approach
Abstract
Background Antidepressant treatment efficacy is low, but might be improved by matching patients to interventions. At present, clinicians have no empirically validated mechanisms to assess whether a patient with depression will respond to a specific antidepressant. We aimed to develop an algorithm to assess whether patients will achieve symptomatic remission from a 12-week course of citalopram.Methods We used patient-reported data from patients with depression (n=4041, with 1949 completers) from level 1 of the Sequenced Treatment Alternatives to Relieve Depression (STAR*D; ClinicalTrials.gov, number NCT00021528) to identify variables that were most predictive of treatment outcome, and used these variables to train a machine-learning model to predict clinical remission. We externally validated the model in the escitalopram treatment group (n=151) of an independent clinical trial (Combining Medications to Enhance Depression Outcomes [COMED]; ClinicalTrials.gov, number NCT00590863).Findings We identified 25 variables that were most predictive of treatment outcome from 164 patient-reportable variables, and used these to train the model. The model was internally cross-validated, and predicted outcomes in the STAR*D cohort with accuracy significantly above chance (64·6% [SD 3·2]; p<0·0001). The model was externally validated in the escitalopram treatment group (N=151) of COMED (accuracy 59·6%, p=0.043). The model also performed significantly above chance in a combined escitalopram-buproprion treatment group in COMED (n=134; accuracy 59·7%, p=0·023), but not in a combined venlafaxine-mirtazapine group (n=140; accuracy 51·4%, p=0·53), suggesting specificity of the model to underlying mechanisms.Interpretation Building statistical models by mining existing clinical trial data can enable prospective identification of patients who are likely to respond to a specific antidepressant.Funding Yale University.
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“Machine learning algorithms, based on both clinical information and biomarkers, are increasingly capable of predicting treatment outcome.58”
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Metadata
- Authors
- Chekroud, A. M., Zotti, R. J., Shehzad, Z., Gueorguieva, R., Johnson, M. K., Trivedi, M. H., Cannon, T. D., Krystal, J. H., & Corlett, P. R.
- Affiliations
- Yale New Haven Hospital (US)
- Capital One (United States) (US)
- Yale University (US)
- The University of Texas Southwestern Medical Center (US)
- Corresponding author
- Chekroud, Adam Mourad
- ORCID
- Venue
- The Lancet Psychiatry
- Publisher
- Elsevier BV
- Published
- 2016-03
- Volume
- 3
- Issue
- 3
- Pages
- 243-250
- ISSN
- 2215-0366 (ISSN-L)
- OpenAlex
- W2257438637
- Cited by
- 676
- References
- 49
- Citations by year
- 2026: 57 · 2025: 86 · 2024: 53 · 2023: 70 · 2022: 74 · 2021: 79 · 2020: 87 · 2019: 76 · 2018: 42 · 2017: 34 · 2016: 17
- FWCI
- 45.64
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Lancet Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Health Sciences › Health Professions › Health Information Management › Artificial Intelligence in Healthcare
- Keywords
- depression, antidepressant treatment response prediction, citalopram, escitalopram, clinical remission, STAR*D, venlafaxine, mirtazapine, patient-reported outcomes, treatment matching, machine learning prediction models, external validation
- MeSH terms
- Machine Learning, Adolescent, Adult, Aged, Algorithms, Antidepressive Agents, Major Depressive Disorder, Humans, Middle Aged, Models, Statistical, Citalopram, Treatment Outcome, Cross-Over Studies, Young Adult
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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