Real-World Outcomes of Lurasidone Augmentation for Treatment-Resistant Bipolar Depression: A Retrospective Observational Analysis

Background: Treatment-resistant bipolar depression (TRBD) is a major challenge in psychiatric practice, leading to marked impairment in functioning and quality of life, and increased healthcare utilization. Despite its clinical relevance, consensus on diagnostic criteria and evidence-based therapeutic strategies remains limited. Within the framework of personalized medicine, identifying effective and well-tolerated options for this heterogeneous population is important. Objective: This study evaluates the short-term effectiveness and tolerability of lurasidone as an adjunctive treatment in TRBD, with attention to its potential role in tailoring interventions to individual clinical profiles. Methods: This four-week, retrospective, multicentre observational study included patients with TRBD receiving lurasidone in augmentation to ongoing pharmacological treatment. Dosages were adjusted according to clinical judgement. Symptom severity was assessed with the Hamilton Depression Rating Scale (HAM-D), Young Mania Rating Scale (YMRS), Hamilton Anxiety Rating Scale (HAM-A), and Brief Psychiatric Rating Scale (BPRS). Changes from baseline to endpoint were analysed with repeated measures ANOVA; missing data were managed with the Last Observation Carried Forward (LOCF) method. Results: Sixty patients were enrolled, of whom one discontinued treatment due to adverse effects. The mean lurasidone dose was 39.8 mg/day. Significant improvements were observed across all scales, with consistent reductions in depressive and anxiety symptoms. Clinical response was achieved in 33.3% of participants, while remission occurred in 3.3%. Adverse events were reported by 68.3% of completers, all mild to moderate. Conclusions: Lurasidone appears to be an effective and generally well-tolerated adjunctive option for TRBD. However, remission rates remained low, underscoring the need for further research. In this perspective, lurasidone may contribute to more individualized treatment strategies for difficult-to-treat patients, although confirmatory studies are required to better define its role within precision psychiatry.