Cross-trial prediction of depression remission using problem-solving therapy: A machine learning approach

Abstract

Background: Psychotherapy is a standard depression treatment; however, determining a patient's prognosis with therapy relies on clinical judgment that is subject to trial-and-error and provider variability.

Purpose: To develop machine learning (ML) algorithms to predict depression remission for patients undergoing 6 months of problem-solving therapy (PST).

Method: Using data from the treatment arm of 2 randomized trials, ML models were trained and validated on ENGAGE-2 (ClinicalTrials.gov, #NCT03841682) and tested on RAINBOW (ClinicalTrials.gov, #NCT02246413) for predictions at baseline and at 2-months. Primary outcome was depression remission using the Depression Symptom Checklist (SCL-20) score < 0.5 at 6 months. Predictor variables included baseline characteristics (sociodemographic, behavioral, clinical, psychosocial) and intervention engagement through 2-months.

Results: Of the 26 candidate variables, 8 for baseline and 11 for 2-months were predictive of depression remission, and used to train the models. The best-performing model predicted remission with an accuracy significantly greater than chance in internal validation using the ENGAGE-2 cohort, at baseline [72.6% (SD = 3.6%), p < 0.0001] and at 2-months [72.3% (5.1%), p < 0.0001], and in external validation with the RAINBOW cohort at baseline [58.3% (0%), p < 0.0001] and at 2-months [62.3% (0%), p < 0.0001]. Model-agnostic explanations highlighted key predictors of depression remission at the cohort and patient levels, including female sex, lower self-reported sleep disturbance, lower sleep-related impairment, and lower negative problem orientation.

Conclusions: ML models using clinical and patient-reported data can predict depression remission for patients undergoing PST, affording opportunities for prospective identification of likely responders, and for developing personalized early treatment optimization along the patient care trajectory.

Keywords: Clinical trials; Machine learning; Precision medicine; Prediction models; Problem-solving therapy.