Lumateperone 42 mg plus ADT improves MADRS scores in MDD with anxious distressLumateperone May Help Depression and Anxiety in Specific Patients

Anxious distress is associated with poor outcomes in the treatment of major depressive disorder (MDD). This exploratory post hoc analysis utilized data from a phase 3 study to investigate adjunctive lumateperone 42 mg efficacy in patients with MDD with inadequate antidepressant therapy (ADT) response and anxious distress. Outpatients (18-65 y) had -defined MDD with inadequate response to 1-2 ADTs in the current depressive episode, Montgomery-Åsberg Depression Rating Scale (MADRS) Total score ≥24, and Clinical Global Impression-Severity (CGI-S) score ≥4 (July 2021-February 2024). Patients were randomized to 6-week oral lumateperone 42 mg+ADT (n=239) or placebo+ADT (n=242). Efficacy was assessed in patients with or without -defined anxious distress. Of 481 patients, 43% met criteria for anxious distress. Lumateperone+ADT significantly improved MADRS Total score from baseline to Day 43 versus placebo+ADT in patients with anxious distress (least squares mean difference vs placebo [LSMD]= -6.8; 95% CI=-9.00 to -4.51; effect size [ES]=0.85; <.0001) or without (LSMD=-3.5; 95% CI=-5.47 to -1.58; ES=0.44; <.001). MADRS response and remission rates at Day 43 were significantly greater with lumateperone+ADT in both subgroups (<.05). At Day 43, lumateperone+ADT significantly improved CGI-S score (<.0001), MADRS inner tension item (<.001), and Quick Inventory of Depressive Symptomatology-Self Report-16 item Total score (<.05) in both subgroups. Generalized Anxiety Disorder-7 item Total score significantly improved at Day 43 with lumateperone+ADT in patients with anxious distress ( <.0001) but did not reach statistical significance in those without anxious distress (=.379). Adjunctive lumateperone 42 mg significantly improved depression and anxiety symptoms in patients with MDD with inadequate ADT response and anxious distress. ClinicalTrials.gov identifier: NCT04985942.