Poster
15
(#15) Lumateperone as Adjunctive Therapy in Patients With Major Depressive Disorder and Anxious Distress
Psych Congress 2025
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-5-diagnosed 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-5-diagnosed 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; P.0001) and CGI-S score (LSMD=−0.9; ES=−0.91; P.0001) from baseline to Day 43 vs placebo+ADT in patients with anxious distress. Lumateperone+ADT significantly improved self-reported depression (QIDS-SR-16 Total score; LSMD=−3.7; ES=−0.80; P.0001) at Day 43 vs placebo+ADT in patients with anxious distress. Patient-reported anxiety (GAD-7 Total score) improved at Day 43 vs placebo+ADT in the ITT (baseline mean: lumateperone+ADT, 9.9; placebo+ADT, 9.6; LSMD=−1.6; ES=−0.43; P.0001) and subgroup with anxious distress (LSMD=−3.24; ES=−0.88; P.0001).
Conclusions: Lumateperone 42mg+ADT improved symptoms of depression and anxiety vs placebo+ADT, indicating lumateperone as a promising adjunctive therapy in patients with MDD with anxious distress.
Short Description: This analysis of a positive, Phase 3, randomized, double-blind, placebo-controlled trial (NCT04985942) investigated efficacy of lumateperone 42mg + antidepressant therapy (ADT) in patients with major depressive disorder (MDD) with inadequate ADT response who also met DSM-5 anxious distress criteria. Lumateperone+ADT significantly improved clinician-rated and/or patient-reported measures of depression and anxiety from baseline to Day 43 vs placebo+ADT. These results indicate lumateperone 42mg as a promising adjunctive therapy in patients with MDD with anxious distress.
Name of Sponsoring Organization(s): Intra-Cellular Therapies, a Johnson & Johnson Company
Methods: Adults with DSM-5-diagnosed 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-5-diagnosed 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; P.0001) and CGI-S score (LSMD=−0.9; ES=−0.91; P.0001) from baseline to Day 43 vs placebo+ADT in patients with anxious distress. Lumateperone+ADT significantly improved self-reported depression (QIDS-SR-16 Total score; LSMD=−3.7; ES=−0.80; P.0001) at Day 43 vs placebo+ADT in patients with anxious distress. Patient-reported anxiety (GAD-7 Total score) improved at Day 43 vs placebo+ADT in the ITT (baseline mean: lumateperone+ADT, 9.9; placebo+ADT, 9.6; LSMD=−1.6; ES=−0.43; P.0001) and subgroup with anxious distress (LSMD=−3.24; ES=−0.88; P.0001).
Conclusions: Lumateperone 42mg+ADT improved symptoms of depression and anxiety vs placebo+ADT, indicating lumateperone as a promising adjunctive therapy in patients with MDD with anxious distress.
Short Description: This analysis of a positive, Phase 3, randomized, double-blind, placebo-controlled trial (NCT04985942) investigated efficacy of lumateperone 42mg + antidepressant therapy (ADT) in patients with major depressive disorder (MDD) with inadequate ADT response who also met DSM-5 anxious distress criteria. Lumateperone+ADT significantly improved clinician-rated and/or patient-reported measures of depression and anxiety from baseline to Day 43 vs placebo+ADT. These results indicate lumateperone 42mg as a promising adjunctive therapy in patients with MDD with anxious distress.
Name of Sponsoring Organization(s): Intra-Cellular Therapies, a Johnson & Johnson Company
