Original Research J Clin Psychiatry June 2024

Efficacy and Safety of Esmethadone (REL-1017) in Patients With Major Depressive Disorder and Inadequate Response to Standard Antidepressants: A Phase 3 Randomized Controlled Trial

JCP 2024;85(3):10.4088/JCP.24m15265

Full Article Read the complete peer-reviewed article in J Clin Psychiatry. Clinical Summary Many patients with major depressive disorder remain symptomatic despite an adequate antidepressant trial, yet current adjunctive options often carry meaningful tolerability burdens. This trial tests whether adjunctive oral esmethadone can improve outcomes in patients with major depressive disorder and inadequate response to standard antidepressants without adding signals for withdrawal, abuse, or major cardiometabolic adverse effects. FAQ Did esmethadone improve depressive symptoms in adults with major depressive disorder who had not responded adequately to standard antidepressants?

Key Takeaways In the intent-to-treat population, adjunctive esmethadone did not separate significantly from placebo on the primary endpoint despite numerically greater improvement on MADRS: mean (SD) change from baseline to day 28 was 15.1 (11.3) versus 12.9 (10.4) (MD: 2.3 (10.9); P =.154; ES=0.21). Clinical Guide How can clinicians identify adults with major depressive disorder who matched this esmethadone trial and apply the study's dosing and monitoring approach?