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

Giorgia Porceddu¹Enrico Pessina²Carlo Ignazio Cattaneo³Vassilis Martiadis⁴Carolina Bianca⁵Giuseppe Maina⁵Gianluca Rosso^5*

• ¹Department of Neurosciences, San Luigi Gonzaga University Hospital, Orbassano, Turin, Italy
• ²Department of Mental Health, Community Mental Health Center, ASL Cuneo 2, Alba, Cuneo, Italy
• ³Department of Mental Health, ASL Biella, Biella, Italy
• ⁴Department of Mental Health, Asl Napoli 1 Centro, Napoli, Italy
• ⁵Department of Neurosciences, University of Turin, Turin, Italy

Introduction: 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. 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 17-item Hamilton Depression Rating Scale (HAM-D), Young Mania Rating Scale (YMRS), and Hamilton Anxiety Rating Scale (HAM-A). Changes from baseline to endpoint were analyzed with repeated measures ANOVA; missing data were managed with the Last Observation Carried Forward (LOCF) method. Results: Sixty patients were enrolled. The mean final lurasidone dose was 51.2 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.