(#11) Lumateperone as Adjunctive Therapy in Patients With Major Depressive Disorder and Anxious Distress

Abstract: Background: Lumateperone is FDA-approved to treat schizophrenia and depressive episodes associated with bipolar I or II disorder. This analysis of a positive, Phase 3, randomized, double-blind, placebo-controlled trial (Study 501, NCT04985942) investigated adjunctive lumateperone 42mg efficacy in patients with major depressive disorder (MDD) with inadequate antidepressant therapy (ADT) response and anxious distress. Methods: Adults with DSM-5ñdiagnosed MDD with inadequate response to 1-2 ADT in the current depressive episode were randomized to 6-week oral lumateperone 42mg+ADT or placebo+ADT. Anxiety was assessed using Generalized Anxiety Disorder-7 (GAD-7) Total score. In patients with DSM-5ñdiagnosed anxious distress Montgomery-Asberg Depression Rating Scale (MADRS) Total, Clinical Global Impression Scale-Severity (CGI-S), and Quick Inventory of Depressive Symptomatology-Self Report-16 item (QIDS-SR-16) Total scores were evaluated. Results: Of 481 patients (modified intent-to-treat [mITT] population), 207 (43.0%) had anxious distress (lumateperone, 109; placebo, 98) at baseline. Lumateperone+ADT improved MADRS Total score (least squares mean difference vs placebo [LSMD]=?6.8; effect size [ES]=?0.85; PShort Description: In this analysis of a positive, Phase 3, randomized, double-blind, placebo-controlled trial (NCT04985942), lumateperone 42mg adjunctive to antidepressant therapy (ADT) significantly improved clinician-rated and patient-reported measures of depression and anxiety from baseline to Day 43 vs placebo+ADT in patients with major depressive disorder (MDD) with inadequate ADT response who also met DSM-5 anxious distress criteria. These results indicate lumateperone as a promising adjunctive therapy in patients with MDD with anxious distress.Name of Sponsoring Organization(s): Intra-Cellular Therapies, Inc.