Search

Objective: The purpose of this study was to examine the effects of REL-1017 (esmethadone), a novel N-methyl-d-aspartate receptor (NMDAR) channel blocker, in patients with major depressive disorder who failed to benefit from one to three standard antidepressant treatments in their current major depressive episode. Methods: A 7-day phase 2 multicenter randomized double-blind placebo-controlled trial, comprising three arms, was conducted to assess the safety, tolerability, pharmacokinetics, and efficacy of two dosages of REL-1017 (25 mg or 50 mg orally once a day). Patients were randomly assigned in a 1:1:1 ratio to placebo (N=22), REL-1017 25 mg/day (N=19), or REL-1017 50 mg/day (N=21). Safety scales included the 4-item Positive Symptom Rating Scale for psychotomimetic symptoms, the Clinician-Administered Dissociative States Scale for dissociative symptoms, the Clinical Opiate Withdrawal Scale for withdrawal signs and symptoms, and the Columbia-Suicide Severity Rating Scale for suicidality. The primary efficacy endpoint was the Montgomery-Åsberg Depression Scale (MADRS) score. All 62 randomly assigned patients were included in the full analysis set population analysis. Results: Patients experienced mild or moderate transient adverse events and no evidence of dissociative or psychotomimetic effects, opioid effects, or withdrawal signs and symptoms. The improvement in MADRS score shown on day 4 in both of the REL-1017 dosage groups was sustained through day 7 (last dose) and day 14 (7 days after the last dose), with effect sizes from 0.7 to 1.0. Conclusions: This trial showed favorable safety, tolerability, and pharmacokinetic profiles and suggests that REL-1017 may have rapid and sustained antidepressant effects compared with placebo in patients with inadequate responses to antidepressant treatments. These results will need confirmation in larger and longer trials. [ABSTRACT FROM AUTHOR]

We present the case of a 61-year-old retired catholic priest, who was adopted at a very young age, with psychiatric history of anxiety and depression presenting for evaluation of at least 4 year memory loss and word finding difficulties. Over the preceding couple of years his cognitive functions had rapidly declined. As a result, he became dependent on his elderly parents for most of his instrumental activities of daily living including administration of medication, financial management, and driving. He continues to be independent in his personal care. His presentation offered diagnostic challenges due to the interplay of anxiety and cognitive disorders involving both memory and language domains. In addition, he resisted to repeat formal neuropsychological evaluation. At the bedside, his poor effort on testing was often blamed on his severe anxiety confounding the clinical picture. Lack of knowledge of his family history and his childhood development, and unclear premorbid functioning complicated the diagnostic formulation. A differential diagnosis ranging from possible functional cognitive disorder to neurodevelopmental disorder and neurodegenerative disorders will be discussed. [ABSTRACT FROM AUTHOR]

Investigates the inactivation of protein kinase A by the amyloid Β-peptide treatment of cultured hippocampal neurons. Symptoms and diagnosis of Alzheimer's disease; Deficits in spatial memory; Inhibition of long-term potentation.