Explainable Counterfactual Reasoning in Depression Medication Selection at Multi-Levels (Personalized and Population)
Xinyu Qin, Mark H. Chignell, Alexandria Greifenberger, Sachinthya Lokuge, Elssa Toumeh, Tia Sternat, Martin Katzman, Lu Wang

TL;DR
This paper uses explainable counterfactual reasoning to identify key depressive symptoms influencing antidepressant choice, improving interpretability of AI decision support in depression treatment.
Contribution
It introduces a novel application of counterfactual explanations to understand symptom-driven medication decisions in depression.
Findings
Random Forest classifier achieved high accuracy (~0.85).
Counterfactuals reveal symptom importance in medication choice.
Method enhances interpretability of AI in clinical settings.
Abstract
Background: This study investigates how variations in Major Depressive Disorder (MDD) symptoms, quantified by the Hamilton Rating Scale for Depression (HAM-D), causally influence the prescription of SSRIs versus SNRIs. Methods: We applied explainable counterfactual reasoning with counterfactual explanations (CFs) to assess the impact of specific symptom changes on antidepressant choice. Results: Among 17 binary classifiers, Random Forest achieved highest performance (accuracy, F1, precision, recall, ROC-AUC near 0.85). Sample-based CFs revealed both local and global feature importance of individual symptoms in medication selection. Conclusions: Counterfactual reasoning elucidates which MDD symptoms most strongly drive SSRI versus SNRI selection, enhancing interpretability of AI-based clinical decision support systems. Future work should validate these findings on more diverse cohorts…
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