Lumateperone as Adjunctive Therapy in Patients With Major Depressive Disorder

作者：Suresh Durgam, Willie Earley, Susan G Kozauer, Changzheng Chen, Hassan Lakkis, Roger S. McIntyre, Stephen M. Stahl · 发表于：The Journal of Clinical Psychiatry · 年份：2025 · DOI：10.4088/jcp.25m15848 · 被引用次数：8 · 研究领域：Treatment of Major Depression、Tryptophan and brain disorders、Stress Responses and Cortisol

Lumateperone, a mechanistically novel antipsychotic, simultaneously modulates serotonin, dopamine, and glutamate neurotransmission. This phase 3, randomized, double-blind, placebo-controlled trial investigated efficacy and safety of adjunctive lumateperone 42 mg in patients with major depressive disorder (MDD) with inadequate antidepressant therapy (ADT) response. -defined MDD with inadequate response to 1 or 2 ADTs in the current depressive episode and Montgomery-Åsberg Depression Rating Scale (MADRS) Total score ≥24, Clinical Global Impression Scale-Severity (CGI-S) score ≥4, and Quick Inventory of Depressive Symptomatology-Self Report-16 item (QIDS-SR-16) score ≥14. Patients were randomized to 6-week oral adjunctive placebo (n=243) or adjunctive lumateperone 42 mg (n=242). Primary and key secondary end points were change from baseline to day 43 in MADRS Total and CGI-S scores. Safety was assessed. < .0001). Lumateperone + ADT was generally well tolerated. Treatment-emergent adverse events (≥5%, twice placebo) were dry mouth (placebo + ADT, 2.1%; lumateperone + ADT, 10.8%), fatigue (2.1%; 9.5%), and tremor (0.4%; 5.0%), with minimal risk for weight gain or cardiometabolic abnormalities. Emergence of suicidal ideation was low (placebo + ADT, 3.5%; lumateperone + ADT, 1.4%). Lumateperone 42 mg adjunctive to ADT significantly improved depression symptoms and disease severity vs adjunctive placebo and was generally well tolerated in patients with MDD with inadequate ADT respons...