A5103004624- Treatment of Major Depression
- Tryptophan and brain disorders
- Bipolar Disorder and Treatment
- Neuroscience and Neuropharmacology Research
- Stress Responses and Cortisol
- Genetics and Neurodevelopmental Disorders
- Pharmacological Effects and Toxicity Studies
- Neurotransmitter Receptor Influence on Behavior
- Electroconvulsive Therapy Studies
- Receptor Mechanisms and Signaling
- Ion channel regulation and function
- Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Schizophrenia research and treatment
- Neurogenesis and neuroplasticity mechanisms
- Metabolism and Genetic Disorders
- Mental Health Research Topics
- Diet and metabolism studies
- Attention Deficit Hyperactivity Disorder
- Neurological and metabolic disorders
- Memory and Neural Mechanisms
- Autism Spectrum Disorder Research
- Child and Adolescent Psychosocial and Emotional Development
- Functional Brain Connectivity Studies
- Electrolyte and hormonal disorders
- Nuclear Receptors and Signaling
University of Oxford
2023-2024
Yale University
2002-2024
Johnson & Johnson (United States)
2011-2022
Janssen (United States)
2012-2021
University of Pennsylvania
2002-2019
Janssen (Belgium)
2015-2019
The University of Texas Southwestern Medical Center
2016-2019
Janssen Scientific Affairs (United States)
2018
The Ohio State University Wexner Medical Center
2018
National Institute of Mental Health
2006-2016
<h3>Context</h3> Existing therapies for major depression have a lag of onset action several weeks, resulting in considerable morbidity. Exploring pharmacological strategies that rapid antidepressant effects within few days and are sustained would an enormous impact on patient care. Converging lines evidence suggest the role glutamatergic system pathophysiology treatment mood disorders. <h3>Objective</h3> To determine whether effect can be achieved with antagonist at...
Context: Existing therapies for bipolar depression have a considerable lag of onset action.Pharmacological strategies that produce rapid antidepressant effects-for instance, within few hours or days-would an enormous impact on patient care and public health.Objective: To determine whether N-methyl-Daspartate-receptor antagonist produces effects in subjects with depression.
About one-third of patients with depression fail to achieve remission despite treatment multiple antidepressants. This study compared the efficacy and safety switching treatment-resistant from an ineffective antidepressant flexibly dosed esketamine nasal spray plus a newly initiated or (active comparator) placebo spray.This was phase 3, double-blind, active-controlled, multicenter conducted at 39 outpatient referral centers. The enrolled adults moderate severe nonpsychotic history...
Controlled studies have shown short-term efficacy of esketamine for treatment-resistant depression (TRD), but long-term effects remain to be established.To assess the nasal spray plus an oral antidepressant compared with placebo in delaying relapse depressive symptoms patients TRD stable remission after induction and optimization course antidepressant.In this phase 3, multicenter, double-blind, randomized withdrawal study conducted from October 6, 2015, February 15, 2018, at outpatient...
Objective: The authors compared the efficacy of standard-of-care treatment plus intranasal esketamine or placebo for rapid reduction symptoms major depression, including suicidality, among individuals at imminent suicide risk. Method: In a double-blind, multicenter, proof-of-concept study, 68 participants were randomly assigned to receive (84 mg) twice weekly 4 weeks, in addition comprehensive treatment. primary endpoint was change score from baseline hours after initial dose on...
Approximately one-third of patients with major depressive disorder (MDD) do not respond to available antidepressants.
Abstract Background About one-third of patients with depression fail to achieve remission despite treatment multiple antidepressants and are considered have treatment-resistant depression. Methods This Phase 3, double-blind, multicenter study enrolled adults moderate-to-severe nonresponse ≥2 in the current episode. Eligible (N = 346) were randomized (1:1:1) twice-weekly nasal spray (esketamine [56 or 84 mg] placebo) plus a newly initiated, open-label, oral antidepressant taken daily for 4...
The neurobiological underpinnings of mood modulation, molecular pathophysiology manic-depressive illness, and therapeutic mechanism stabilizers are largely unknown. extracellular signal-regulated kinase (ERK) pathway is activated by neurotrophins other neuroactive chemicals to produce their effects on neuronal differentiation, survival, regeneration, structural functional plasticity. We found that lithium valproate, commonly used for the treatment stimulated ERK in rat hippocampus frontal...
Objective: Ketamine, an N-methyl-d-aspartate glutamate receptor antagonist, has demonstrated a rapid-onset antidepressant effect in patients with treatment-resistant depression. This study evaluated the efficacy of twice- and thrice-weekly intravenous administration ketamine sustaining initial effects Method: In multicenter, double-blind study, adults (ages 18–64 years) depression were randomized to receive either (0.5 mg/kg body weight) or placebo, administered over 40 minutes, two three...
Glucocorticoids play an important biphasic role in modulating neural plasticity; low doses enhance plasticity and spatial memory behavior, whereas chronic, higher produce inhibition. We found that 3 independent measures of mitochondrial function-mitochondrial oxidation, membrane potential, calcium holding capacity-were regulated by long-term corticosterone (CORT) treatment inverted "U"-shape. This regulation function CORT correlated with neuroprotection; is, had a neuroprotective effect,...
Elderly patients with major depression have a poorer prognosis, are less responsive to treatment, and show greater functional decline compared younger patients, highlighting the need for effective treatment.This phase 3 double-blind study randomized treatment-resistant (TRD) ≥65 years (1:1) flexibly dosed esketamine nasal spray new oral antidepressant (esketamine/antidepressant) or placebo (antidepressant/placebo). The primary endpoint was change in Montgomery-Åsberg Depression Rating Scale...
Manic-depressive illness has been conceptualized as a neurochemical illness. However, brain imaging and postmortem studies reveal gray-matter reductions, well neuronal glial atrophy loss in discrete regions of manic-depressive patients. The roles such cerebral morphological deficits the neuropathophysiology therapeutic mechanisms are unknown. Valproate (2-propylpentanoate) is commonly used mood stabilizer. ERK (extracellular signal-regulated kinase) pathway by neurotrophic factors to...
BackgroundThe purpose of this study was to assess the efficacy and safety explore dose response esketamine intravenous (IV) infusion in patients with treatment-resistant depression (TRD).MethodsThis multicenter, randomized, placebo-controlled trial conducted 30 TRD. Patients were randomly assigned 1:1:1 receive an IV .20 mg/kg or .40 placebo over 40 minutes on day 1. The primary end point change Montgomery–Åsberg Depression Rating Scale total score from 1 (baseline) 2. Nonresponders who...
OBJECTIVE: This study was designed to assess possible antidepressant effects of memantine, a selective N-methyl-D-aspartate (NMDA) receptor antagonist in humans. METHOD: In double-blind, placebo-controlled study, 32 subjects with major depression were randomly assigned receive memantine (5–20 mg/day) (N=16) or placebo for 8 weeks. Primary efficacy assessed by performance on the Montgomery-Åsberg Depression Rating Scale (MADRS). RESULTS: The linear mixed models total MADRS scores showed no...