Individual Prediction of Optimal Treatment Allocation Between Electroconvulsive Therapy or Ketamine using the Personalized Advantage Index

Abstract

Abstract Introduction: Electroconvulsive therapy (ECT) and ketamine are two effective treatments for depression with similar efficacy; however, individual patient outcomes may be improved by models that predict optimal treatment assignment. Here, we adapt the Personalized Advantage Index (PAI) algorithm using machine learning to predict optimal treatment assignment between ECT and ketamine using medical record data from a large, naturalistic patient cohort. We hypothesized that patients who received a treatment predicted to be optimal would have significantly better outcomes following treatment compared to those who received a non-optimal treatment. Methods:Data on 2526 ECT and 235 mixed IV ketamine and esketamine patients from McLean Hospital was aggregated. Depressive symptoms were measured using the Quick Inventory of Depressive Symptomatology (QIDS) before and during acute treatment. Patients were matched between treatments on pretreatment QIDS, age, inpatient status, and psychotic symptoms using a 1:1 ratio yielding a sample of 470 patients (n=235 per treatment). Random forest models were trained and predicted differential patientwise minimum QIDS scores achieved during acute treatment (min-QIDS) scores for ECT and ketamine using pretreatment patient measures. Analysis of Shapley Additive exPlanations (SHAP) values identified predictors of differential outcomes between treatments. Results: Twenty-seven percent of patients with the largest PAI scores who received a treatment predicted optimal had significantly lower min-QIDS scores compared to those who received a non-optimal treatment (mean difference=1.6, t=2.38, q<0.05, Cohen’s D=0.36). Analysis of SHAP values identified prescriptive pretreatment measures. Conclusions: Patients assigned to a treatment predicted to be optimal had significantly better treatment outcomes. Our model identified pretreatment patient factors captured in medical records that can provide interpretable and actionable guidelines treatment selection.