Abstract:

Background With the emergence of evidence-based treatments for treatment-resistant depression, strategies to identify individuals at greater risk for treatment resistance early in the course of illness could have clinical utility. We sought to develop and validate a model to predict treatment resistance in major depressive disorder using coded clinical data from the electronic health record. Methods We identified individuals from a large health system with a diagnosis of major depressive disorder receiving an index antidepressant prescription, and used a tree-based machine learning classifier to build a risk stratification model to identify those likely to experience treatment resistance. The resulting model was validated in a second health system. Results In the second health system, the extra trees model yielded an AUC of 0.652 (95% CI: 0.623–0.682); with sensitivity constrained at 0.80, specificity was 0.358 (95% CI: 0.300–0.413). Lift in the top quintile was 1.99 (95% CI: 1.76–2.22). Including additional data for the 4 weeks following treatment initiation did not meaningfully improve model performance. Limitations The extent to which these models generalize across additional health systems will require further investigation. Conclusion Electronic health records facilitated stratification of risk for treatment-resistant depression and demonstrated generalizability to a second health system. Efforts to improve upon such models using additional measures, and to understand their performance in real-world clinical settings, are warranted.

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