Original Research J Clin Psychiatry September 2026

Lumateperone as Adjunctive Therapy in Patients With Major Depressive Disorder and Anxious Distress: Post Hoc Analysis of a Phase 3, Randomized, Double-Blind Trial

JCP 2026;87(3):10.4088/JCP.26m16409

Full Article Read the complete peer-reviewed article in J Clin Psychiatry. Clinical Summary Patients with major depressive disorder and anxious distress often have poorer outcomes and are less likely to respond to antidepressants, yet clinicians have limited evidence to guide augmentation choices. This analysis addresses whether adjunctive lumateperone improves both depressive and anxiety symptoms in this difficult-to-treat subgroup after inadequate antidepressant therapy response. FAQ Did adjunctive lumateperone help patients with major depressive disorder and anxious distress after an inadequate antidepressant response?

Key Takeaways Patients meeting DSM-5 anxious distress criteria appeared to derive a larger antidepressant effect than those without anxious distress, with Day 43 MADRS effect sizes of 0.85 versus 0.44 and CGI-S effect sizes of 0.91 versus 0.50. Clinical Guide How should clinicians identify patients with major depressive disorder and anxious distress who may be appropriate for adjunctive lumateperone after inadequate antidepressant response?