Clinical Predictors of Lithium Response in Patients with Bipolar Disorder: Potential Predictive Role of Chronotype, Rumination and Traumatic Events

INTRODUCTION: Bipolar Disorders (BD) are severe, recurrent, and well-characterized psychiatric conditions with lithium as the first-line approved treatment for BD. This study aims to evaluate lithium response using the ALDA scale and to identify reliable predictors in a cohort of patients with BD. METHODS: In this cross-sectional observational study, one hundred and fourteen consecutively recruited patients with a primary diagnosis of BD type I or II were included between June 2022 and June 2025. Sociodemographic and clinical characteristics were collected through a semi-structured interview. Lithium response was retrospectively assessed using the ALDA scale. Psychometric instruments (CTQ, MEQ, MWQ, DDFS, RRS, BIS-11) were administered. Logistic regression analyses were performed to identify independent predictors of lithium response. RESULTS: Forty-one (36%) individuals were classified as lithium responders according to the ALDA Scale. Lithium responders were younger, engaged in physical activity more frequently, were more frequently diagnosed with BD type II, had a shorter illness duration, a Manic-Depressive-Interval (MDI) course, and showed fewer residual symptoms. Non-responders were associated with rapid cycling, psychotic symptoms, more hospitalizations, and illicit substance use. Childhood trauma, impulsivity, and rumination were more common among non-responders, while morning chronotype was more prevalent among responders. In the regression analysis, the MDI pattern, higher total scores for attentional impulsivity and rumination, and morning chronotype were all significantly associated with lithium responsiveness. On the other hand, the presence of psychotic symptoms, a history of ≥ 5 hospitalizations, comorbid substance use, and higher scores of emotional abuse were associated with a lower likelihood of response to lithium. DISCUSSION: Integrating the evaluation of trauma history, impulsive profiles, ruminative tendencies, and circadian features into clinical assessment may enhance the prediction of lithium response. CONCLUSION: Our findings support the development of personalized treatment strategies for BD.