Machine Learning in Healthcare Open access Peer reviewed

Phenotyping antidepressant treatment response with deep learning in electronic health records

Yi-han Sheu, Colin Magdamo, Matthew Miller, Sudeshna Das and 2 more

Translational Psychiatry | Jul 10, 2026 | 5 citations

Abstract

Abstract

ABSTRACT Efficient, accurate phenotyping for antidepressant treatment response in electronic health records (EHRs) could facilitate precision psychiatry applications but remains a challenge. Increasingly, artificial intelligence methods using “deep learning” applied to clinical data have shown promise in complex classification problems. Here, we systematically evaluate the performance of eight deep-learning-based natural language processing models in classifying response to antidepressants in a large real-world healthcare setting. We obtained data spanning 1990-2018 for adults with depression and a co-occurring antidepressant prescription from the EHR data warehouse of the Mass General Brigham healthcare system (n=111,572). Clinical notes were collected for the following time windows after antidepressant initiation: (1) 2 days to 4 weeks, (2) 4–12 weeks, and (3) 12–26 weeks. A stratified random sample of these note sets (total 4,299 across time periods) were manually reviewed to classify response status as “improved” or “no evidence of improvement” in depression symptoms. All models performed well, with areas under the receiver operator curve (AUROC) of at least 0.80. Positive predictive values (PPVs) ranged from 0.72 – 0.91. In general, models incorporating more information-dense and longer text sequences performed better than others. The best performing model (Longformer-large with sliding window) had an AUROC = 0.88 and PPV = 0.84 at a specificity of 0.88. Our results indicate that deep learning methods applied to EHR data can accurately classify antidepressant response in a real-world healthcare setting. Automated treatment response classification may facilitate a range of research and clinical decision support applications.

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Authors

Researchers on this paper

Yi-han Sheu

first | Broad Institute | ORCID 0000-0002-2767-0851

Colin Magdamo

middle | Harvard University | ORCID 0000-0001-8965-4630

Matthew Miller

middle | Northeastern University | ORCID 0000-0002-5251-7939

Sudeshna Das

middle | Harvard University | ORCID 0000-0002-9486-6811

Deborah Blacker

middle | Harvard University | ORCID 0000-0001-6107-7376

Jordan W. Smoller

last | Broad Institute | ORCID 0000-0002-0381-6334

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Citation

BibTeX

@article{Sheu2026Phenotyping,
  title = {Phenotyping antidepressant treatment response with deep learning in electronic health records},
  author = {Yi-han Sheu and Colin Magdamo and Matthew Miller and Sudeshna Das and Deborah Blacker and Jordan W. Smoller},
  journal = {Translational Psychiatry},
  year = {2026},
  doi = {10.1038/s41398-026-04266-1},
  url = {https://doi.org/10.1038/s41398-026-04266-1}
}

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