Effect of Lumateperone (ITI-007) on Quality of Life and Functional Disability in the Treatment of Bipolar Depression

Abstract

Introduction. In patients with bipolar disorder, depression symptoms are associated with greater reduction in function and quality of life than hypomania/mania symptoms. Lumateperone (LUMA), is an FDA‐approved antipsychotic to treat schizophrenia and depressive episodes associated with bipolar I or bipolar II disorder. In a recent phase 3 clinical trial (Study 404, NCT03249376) in people with bipolar depression, LUMA 42 mg monotherapy significantly improved symptoms of depression compared with placebo (PBO). This analysis of Study 404 investigated the effects of LUMA on functional disability and quality of life as measured using the secondary outcome measure, the Quality of Life Enjoyment and Satisfaction Questionnaire‐Short Form (Q‐LES‐Q‐SF). Methods. Patients (18‐75 years) with bipolar I or bipolar II disorder experiencing a major depressive episode (MontgomeryÅsberg Depression Rating Scale [MADRS] Total score ≥20 and Clinical Global Impression Scale‐Bipolar Version‐Severity [CGIBP‐ S] score ≥4) were randomized to LUMA 42 mg or PBO orally, once daily in the evening for 6 weeks. The primary endpoint was the change from baseline to Day 43 in MADRS Total score, analyzed using a mixed‐effects model for repeated measures (MMRM) approach in the intent‐to‐treat population (ITT). This post hoc analysis evaluated the mean change from baseline to Day 43 in the Q‐LES‐Q‐SF individual item scores using an analysis of covariance with last observation carried forward (ANCOVALOCF) in the ITT. Categorical shifts in individual items were also analyzed. Results. The ITT comprised 376 patients (LUMA 42 mg, 188; PBO, 188). Patients in the LUMA 42 mg group had significantly greater improvement on MADRS Total score change from baseline to Day 43 compared with PBO (least squares mean difference vs PBO [LSMD], ‐4.585; 95% CI, ‐6.344 to‐2.826; effect size vs PBO [ES], ‐0.56; P <0.05). Overall life satisfaction also significantly improved withLUMAtreatment (P=.0016). The largest improvements with LUMA 42 mg compared with PBO (ES>0.3,) were seen for the ability to function in daily life, family relationships, household activities, leisure time activities, and mood (all LSMD=0.3; all P