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, Marco Pappagallo
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引用次数: 0
Abstract
Background: Esmethadone is a novel N-methyl-D-aspartate receptor (NMDAR) uncompetitive antagonist in development as adjunctive treatment for major depressive disorder (MDD).
Methods: This 12-month, open-label study evaluated the safety and efficacy of esmethadone in patients with MDD meeting DSM-5 criteria who completed 1 of 3 double-blind studies (rollover) and in patients with MDD and no prior participation in esmethadone studies (de novo). 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.
Results: Safety population included 624 patients; FAS included 586 patients (384 rollover 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.
Conclusions: Long-term treatment with esmethadone was safe and well tolerated. The antidepressant efficacy of esmethadone was sustained over 12 months.
期刊介绍：
For over 75 years, The Journal of Clinical Psychiatry has been a leading source of peer-reviewed articles offering the latest information on mental health topics to psychiatrists and other medical professionals.The Journal of Clinical Psychiatry is the leading psychiatric resource for clinical information and covers disorders including depression, bipolar disorder, schizophrenia, anxiety, addiction, posttraumatic stress disorder, and attention-deficit/hyperactivity disorder while exploring the newest advances in diagnosis and treatment.
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