title: 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).
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Building statistical models by mining existing clinical trial data can enable prospective identification of patients who are likely to respond to a specific antidepressant.
  
  
  BACKGROUND
  Yale University.
authors.affiliation: 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.
authors.forename: Adam Mourad
authors.initials: AM
authors.lastname: Chekroud
authors.affiliation: Capital One, McLean, VA, USA.
authors.forename: Ryan Joseph
authors.initials: RJ
authors.lastname: Zotti
authors.affiliation: Department of Psychology, Yale University, New Haven, CT, USA.
authors.forename: Zarrar
authors.initials: Z
authors.lastname: Shehzad
authors.affiliation: Department of Biostatistics, Yale University, New Haven, CT, USA.
authors.forename: Ralitza
authors.initials: R
authors.lastname: Gueorguieva
authors.affiliation: Department of Psychology, Yale University, New Haven, CT, USA.
authors.forename: Marcia K
authors.initials: MK
authors.lastname: Johnson
authors.affiliation: Department of Psychiatry, UT Southwestern, Dallas, TX, USA.
authors.forename: Madhukar H
authors.initials: MH
authors.lastname: Trivedi
authors.affiliation: Department of Psychology, Yale University, New Haven, CT, USA; Department of Psychiatry, Yale University, New Haven, CT, USA.
authors.forename: Tyrone D
authors.initials: TD
authors.lastname: Cannon
authors.affiliation: Department of Psychiatry, Yale University, New Haven, CT, USA.
authors.forename: John Harrison
authors.initials: JH
authors.lastname: Krystal
authors.affiliation: Department of Psychiatry, Yale University, New Haven, CT, USA.
authors.forename: Philip Robert
authors.initials: PR
authors.lastname: Corlett
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000465:Algorithms; D000928:Antidepressive Agents / Q000627:therapeutic use*; D015283:Citalopram / Q000627:therapeutic use*; D018592:Cross-Over Studies; D003865:Major Depressive Disorder / Q000188:drug therapy*; D006801:Humans; D000069550:Machine Learning; D008875:Middle Aged; D015233:Models, Statistical; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000928:Antidepressive Agents; D015283:Citalopram