Evaluation of a Machine Learning Model Based on Pretreatment Symptoms and Electroencephalographic Features to Predict Outcomes of Antidepressant Treatment in Adults With Depression

Abstract

Despite the high prevalence and potential outcomes of major depressive disorder, whether and how patients will respond to antidepressant medications is not easily predicted. To identify the extent to which a machine learning approach, using gradient-boosted decision trees, can predict acute improvement for individual depressive symptoms with antidepressants based on pretreatment symptom scores and electroencephalographic (EEG) measures. This prognostic study analyzed data collected as part of the International Study to Predict Optimized Treatment in Depression, a randomized, prospective open-label trial to identify clinically useful predictors and moderators of response to commonly used first-line antidepressant medications. Data collection was conducted at 20 sites spanning 5 countries and including 518 adult outpatients (18-65 years of age) from primary care or specialty care practices who received a diagnosis of current major depressive disorder between December 1, 2008, and September 30, 2013. Patients were antidepressant medication naive or willing to undergo a 1-week washout period of any nonprotocol antidepressant medication. Statistical analysis was conducted from January 5 to June 30, 2019. Participants with major depressive disorder were randomized in a 1:1:1 ratio to undergo 8 weeks of treatment with escitalopram oxalate (n = 162), sertraline hydrochloride (n = 176), or extended-release venlafaxine hydrochloride (n = 180). The primary objective was to predict improvement in individual symptoms, defined as the difference in score for each of the symptoms on the 21-item Hamilton Rating Scale for Depression from baseline to week 8, evaluated using the C index. The resulting data set contained 518 patients (274 women; mean [SD] age, 39.0 [12.6] years; mean [SD] 21-item Hamilton Rating Scale for Depression score improvement, 13.0 [7.0]). With the use of 5-fold cross-validation for evaluation, the machine learning model achieved C index scores of 0.8 or higher on 12 of 21 clinician-rated symptoms, with the highest C index score of 0.963 (95% CI, 0.939-1.000) for loss of insight. The importance of any single EEG feature was higher than 5% for prediction of 7 symptoms, with the most important EEG features being the absolute delta band power at the occipital electrode sites (O1, 18.8%; Oz, 6.7%) for loss of insight. Over and above the use of baseline symptom scores alone, the use of both EEG and baseline symptom features was associated with a significant increase in the C index for improvement in 4 symptoms: loss of insight (C index increase, 0.012 [95% CI, 0.001-0.020]), energy loss (C index increase, 0.035 [95% CI, 0.011-0.059]), appetite changes (C index increase, 0.017 [95% CI, 0.003-0.030]), and psychomotor retardation (C index increase, 0.020 [95% CI, 0.008-0.032]). This study suggests that machine learning may be used to identify independent associations of symptoms and EEG features to predict antidepressant-associated improvements in specific symptoms of depression. The approach should next be prospectively validated in clinical trials and settings. ClinicalTrials.gov Identifier: NCT00693849.