Prediction of lithium response using clinical data

Objective: Promptly establishing maintenance therapy could reduce morbidity and mortality in patients with bipolar disorder. Using a machine learning approach, we sought to evaluate whether lithium responsiveness (LR) is predictable using clinical markers. Method: Our data are the largest existing sample of direct interview-based clinical data from lithium-treated patients (n = 1266, 34.7% responders), collected across seven sites, internationally. We trained a random forest model to classify LR—as defined by the previously validated Alda scale—against 180 clinical predictors. Results: Under appropriate cross-validation procedures, LR was predictable in the pooled sample with an area under the receiver operating characteristic curve of 0.80 (95% CI 0.78–0.82) and a Cohen kappa of 0.46 (0.4–0.51). The model demonstrated a particularly low false-positive rate (specificity 0.91 [0.88–0.92]). Features related to clinical course and the absence of rapid cycling appeared consistently informative. Conclusion: Clinical data can inform out-of-sample LR prediction to a potentially clinically relevant degree. Despite the relevance of clinical course and the absence of rapid cycling, there was substantial between-site heterogeneity with respect to feature importance. Future work must focus on improving classification of true positives, better characterizing between- and within-site heterogeneity, and further testing such models on new external datasets.