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Lancet Psychiatry. 2016 Mar;3(3):243-50. doi: 10.1016/S2215-0366(15)00471-X. Epub 2016 Jan 21.

Cross-trial prediction of treatment outcome in depression: a machine learning approach.

Author information

1
Department of Psychology, Yale University, New Haven, CT, USA; Centre for Outcomes Research and Evaluation, Yale-New Haven Hospital, New Haven, CT, USA. Electronic address: adam.chekroud@yale.edu.
2
Capital One, McLean, VA, USA.
3
Department of Psychology, Yale University, New Haven, CT, USA.
4
Department of Biostatistics, Yale University, New Haven, CT, USA.
5
Department of Psychiatry, UT Southwestern, Dallas, TX, USA.
6
Department of Psychology, Yale University, New Haven, CT, USA; Department of Psychiatry, Yale University, New Haven, CT, USA.
7
Department of Psychiatry, Yale University, New Haven, CT, USA.

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.

PMID:
26803397
DOI:
10.1016/S2215-0366(15)00471-X
[Indexed for MEDLINE]

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