Real-world outcomes of lurasidone augmentation for treatment-resistant bipolar depression: a retrospective observational analysis

Giorgia Porceddu; Enrico Pessina; Carlo Ignazio Cattaneo; Vassilis Martiadis; Carolina Bianca; Giuseppe Maina; Gianluca Rosso

doi:10.3389/fpsyt.2026.1744056

Real-world outcomes of lurasidone augmentation for treatment-resistant bipolar depression: a retrospective observational analysis

Front Psychiatry. 2026 Feb 19:17:1744056. doi: 10.3389/fpsyt.2026.1744056. eCollection 2026.

Authors

Giorgia Porceddu¹, Enrico Pessina², Carlo Ignazio Cattaneo³, Vassilis Martiadis⁴, Carolina Bianca⁵, Giuseppe Maina⁵, Gianluca Rosso⁵

Affiliations

¹ Department of Neurosciences, San Luigi Gonzaga University Hospital, Turin, Italy.
² Department of Mental Health, Community Mental Health Center, Local Health Unit of Cuneo 2, Cuneo, Italy.
³ Department of Mental Health, Local Health Unit of Biella, Biella, Italy.
⁴ Department of Mental Health, Local Health Unit of Napoli 1 Centro, Napoli, Italy.
⁵ Department of Neurosciences, University of Turin, Turin, Italy.

Abstract

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.

Keywords: TRBD; bipolar depression; bipolar disorder; hamilton depression rating scale; lurasidone; treatment-resistance.