Long-Term Safety and Efficacy of Esmethadone in Patients With Major Depressive Disorder

作者：Maurizio Fava, Luca Pani, Sara De Martin, Andrew J. Cutler, Charles W. Gorodetzky, Frank J. Vocci, Frank L. Sapienza, Thomas R. Kosten, Cornelia Kröger, Paggard Champasa, Clotilde Guidetti, Stefano Comai, Andrea Mattarei, Franco Folli, David Bushnell, Sergio Traversa, Charles E. Inturrisi, Paolo L. Manfredi, M. Pappagallo · 发表于：The Journal of Clinical Psychiatry · 年份：2025 · DOI：10.4088/jcp.24m15438 · 被引用次数：8 · 研究领域：Treatment of Major Depression、Neurotransmitter Receptor Influence on Behavior、Attention Deficit Hyperactivity Disorder

-methyl-D-aspartate receptor (NMDAR) uncompetitive antagonist in development as adjunctive treatment for major depressive disorder (MDD). ). Safety was assessed from adverse events, laboratory parameters, vital signs, electrocardiogram, and the Columbia-Suicide Severity Rating Scale. Efficacy assessments used measures of depression, anxiety, sleep, sexual function, cognitive function, and quality of life. The safety population comprised patients who received at least 1 dose of study drug, and the full analysis set (FAS) comprised patients who had at least 1 postbaseline efficacy assessment. and 202 de novo); mean age was 42.9 (13.6) years, and mean baseline Montgomery-Asberg Depression Rating Scale (MADRS10) was 34.5 (4.8). Most common treatment-related treatment emergent adverse events were headache (4.6%), nausea (4.2%), and dizziness (2.6%). There were no signals of meaningful neurological, cardiovascular, metabolic, or sexual adverse events and no case of suicide or suicidal attempt. For the FAS, mean (SD) change from baseline for MADRS10 at 3, 6, 9, and 12 months was -20.1 (10.7), -21.0 (10.8), -21.6 (10.7), and -21.6 (10.4). For the de novo population, mean (SD) was -19.9 (10.0), -19.9 (10.4), -20.1 (10.2), and -22.5 (9.7). Consistent improvements occurred with other tested efficacy measures. Long-term treatment with esmethadone was safe and well tolerated. The antidepressant efficacy of esmethadone was sustained over 12 months. ClinicalTrials.gov identifier: NCT0485576...