scholarly journals Dextromethorphan/Bupropion: A Novel Oral NMDA (N-methyl-d-aspartate) Receptor Antagonist with Multimodal Activity

CNS Spectrums ◽  
2019 ◽  
Vol 24 (5) ◽  
pp. 461-466 ◽  
Author(s):  
Stephen M. Stahl
Keyword(s):  
Rapid Onset ◽  
Mechanisms Of Action ◽  
Second Line ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Major Depressive ◽  
Therapeutic Benefits ◽  
Aspartate Receptor ◽  
Adequate Response ◽  
Resistant Depression

Although currently available antidepressants increase monoamine levels soon after the start of treatment, therapeutic benefits are often delayed by several weeks and the majority of patients with major depressive disorder fail to achieve an adequate response to first- or second-line therapies targeting monoamines. The recent approval of the NMDA (N-methyl-d-aspartate) antagonist esketamine given intranasally for treatment-resistant depression has reinforced the need for agents with rapid onset with alternate mechanisms of action. Dextromethorphan/bupropion, an investigational medicine currently in development, is one such candidate.

scholarly journals Esketamine in Treatment Resistant Depression: The Way to Remission

2021 ◽  
pp. 35-39
Author(s):  
João Facucho-Oliveira ◽  
Daniel Esteves-Sousa ◽  
Bruno Prates ◽  
Rui Neves ◽  
Pedro Varandas
Keyword(s):  
Depressive Symptoms ◽  
Behavioral Therapy ◽  
Symptomatic Relief ◽  
European Medicines Agency ◽  
Caucasian Woman ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Major Depressive ◽  
Aspartate Receptor ◽  
Resistant Depression

Major depressive disorder affects an estimate of 5% of the population with nearly 1‑third of patients failing to achieve remission with conventional pharmacological treatment. Esketamine, a novel rapid‑acting antidepressant, with a noncompetitive antagonism on N‑methyl‑D‑Aspartate receptor, have been recently approved by Food and Drug Administration (FDA) and European Medicines Agency (EMA) for treatment‑resistant depression. Here, we report a clinical case of a 42‑year‑old Caucasian woman who endured many years with severe depressive symptoms and high functional impairment. Previous treatments included cognitive behavioral therapy, numerous pharmacological trials with antidepressants and augmentation agents, and neurostimulation approaches. Upon treatment with esketamine, the patient presented remarkable clinical recovery. Psychometric assessments determined an acute reduction on the MADRS score after 1 week and progressive recovery of the depressive symptoms on the following weeks. Likewise, PHQ‑9 scale assessments, evaluating the relative frequency of depressive symptoms. and the Sheehan scale, assessing functional recovery, also determined a pronounced symptomatic relief.

scholarly journals Ketamine for the treatment of major depressive disorder and bipolar depression: A review of the literature

2017 ◽  
Vol 7 (1) ◽  
pp. 16-23 ◽  
Author(s):  
Sarah E. Grady ◽  
Travis A. Marsh ◽  
Allison Tenhouse ◽  
Kelsey Klein
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Bipolar Depression ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Major Depressive ◽  
Randomized Controlled ◽  
The Past ◽  
Aspartate Receptor ◽  
Resistant Depression

Abstract Introduction: Over the past decade, ketamine has been studied for major depressive disorder and bipolar depression. Ketamine is believed to exert its antidepressant properties through N-methyl-D-aspartate receptor antagonism. Methods: Study authors completed a literature review of seven randomized controlled trials of ketamine usage in major depressive disorder and bipolar depression. Results: Ketamine demonstrated a statistically significant improvement over placebo or midazolam in major depressive disorder. Ketamine also exhibited a statistically significant improvement over placebo in bipolar depression. Discussion: Ketamine has shown promise in quickly reducing symptoms in patients with treatment resistant depression and bipolar depression. Using ketamine may be helpful for patients that have exhausted other therapeutic options.

The potential anti-depressant properties of dexmedetomidine infusion: a review of mechanistic, preclinical, and clinical evidence

2020 ◽  
Vol 31 (6) ◽  
pp. 649-658
Author(s):  
Mohammed Al-Alawi ◽  
Elisa Brietzke ◽  
Adriana Carvalhal ◽  
Claudio N. Soares
Keyword(s):  
Clinical Evidence ◽  
Rapid Onset ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Major Depressive ◽  
Onset Of Action ◽  
Antidepressant Agent ◽  
Antidepressant Effects ◽  
Resistant Depression ◽  
Dexmedetomidine Infusion

AbstractMajor depressive disorder (MDD) is a highly prevalent and disabling condition for which the currently available treatments are not fully effective. Existing unmet needs include rapid onset of action and optimal management of concurrent agitation. Dexmedetomidine (DEX) is a selective and potent α2-adrenergic receptor (α2-AR) agonist, with unique pharmacokinetic and pharmacodynamic properties. In this review, we discuss pre-clinical and clinical studies which focused on DEX in the context of its putative antidepressant effects for the management of MDD. Preliminary data support DEX as an antidepressant with fast onset of action, which would be especially helpful for patients experiencing treatment resistant depression, and agitation. We further explore the mechanistic and clinical implications of considering DEX as a putative antidepressant agent, and the next steps to explore the efficacy of low dose DEX infusion among patients with treatment resistant depression.

scholarly journals Using Oral and Intranasal Dosage Forms of Ketamine for Managing Treatment-Resistant Depression: A Review of the Literature

2016 ◽  
Vol 4 (2) ◽  
pp. 64-71 ◽  
Author(s):  
Patrick Arthur Twohig ◽  
Vaughn Huckfeldt
Keyword(s):  
Health Care ◽  
Side Effects ◽  
Care Setting ◽  
Dosage Forms ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Similar Reduction ◽  
Aspartate Receptor ◽  
Pubmed Database ◽  
Resistant Depression

A lack of effective treatment for patients with treatment-resistant depression (TRD) has led to the evaluation of ketamine, an N-methyl- D-aspartate receptor antagonist. Despite the demonstrated short-term benefits of using intravenous (IV) ketamine, side effects and the difficulty in administering ketamine outside the health-care setting has raised interest in alternative dosage forms. Research articles evaluating oral or intranasal (IN) ketamine were retrieved from the PubMed database. Patients who received oral or IN ketamine experienced a similar reduction in depressive symptoms within 24 hours of treatment and fewer side effects compared to patients who received IV ketamine. Novel administration forms of ketamine provide an opportunity for patients with TRD to achieve remission with fewer adverse side effects. Future studies should continue to evaluate these administration strategies in the hope of promoting ketamine’s use outside health-care settings and for longer time periods.

Depression

2018 ◽  
Author(s):  
Raymond W. Lam
Keyword(s):  
Depressive Disorders ◽  
Special Populations ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Major Depressive ◽  
Basic Principles ◽  
Medically Ill ◽  
Dsm 5 ◽  
Resistant Depression

Depression, Third Edition provides a succinct clinical guide for the recognition, diagnosis, management, and modalities of treatment of depressive disorders. This new edition includes the DSM-5 diagnostic criteria, updates the latest neurobiological and psychological findings, and summarizes the Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder. The initial chapters deal with the epidemiology, pathogenesis, clinical features, and diagnosis of depression. Basic principles of clinical management are provided, as well as individual chapters dealing with the spectrum of available treatments for depression, including pharmacological, psychological, somatic, and complementary medicine approaches. A final chapter focuses on treatment-resistant depression (TRD) and other special populations including peripartum, elderly and medically ill, and children and adolescents.

Deep brain stimulation for treatment-resistant depression: Efficacy, safety and mechanisms of action

2012 ◽  
Vol 36 (8) ◽  
pp. 1920-1933 ◽  
Author(s):  
Rodney J. Anderson ◽  
Mark A. Frye ◽  
Osama A. Abulseoud ◽  
Kendall H. Lee ◽  
Jane A. McGillivray ◽  
...  
Keyword(s):  
Deep Brain Stimulation ◽  
Brain Stimulation ◽  
Mechanisms Of Action ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Resistant Depression ◽  
Deep Brain

scholarly journals Treatment-Resistant Depression in a Real-World Setting: First Interim Analysis of Characteristics, Healthcare Resource Use, and Utility Values of the FondaMental Cohort

2020 ◽  
Vol 10 (12) ◽  
pp. 962
Author(s):  
Antoine Yrondi ◽  
Djamila Bennabi ◽  
Emmanuel Haffen ◽  
Delphine Quelard ◽  
Ludovic Samalin ◽  
...  
Keyword(s):  
Resource Use ◽  
Healthcare Resource ◽  
The Other ◽  
Health State ◽  
Treatment Resistant Depression ◽  
Healthcare Resource Use ◽  
Treatment Resistant ◽  
Utility Value ◽  
Major Depressive ◽  
Resistant Depression

Background: Major depressive disorder (MDD) is among the most common psychiatric disorders. One-third of patients are usually unresponsive to several lines of treatment. This study aimed to describe the FondaMental French cohort of patients with treatment-resistant depression (TRD) and to estimate utility and healthcare resource use outcomes. Methods: Patients with TRD were evaluated prospectively over four years (baseline, 6, 12, 18, 24, 36 and 48 months) in a real-world clinical setting. Interim analyses focused on the first two consecutive years. Four MDD-related states (major depressive episode (MDE), response, remission, recovery) were defined based on the MADRS (Montgomery–Åsberg depression rating scale) and other clinical events. Health status was assessed with the EuroQol 5 Dimensions 5 Level (EQ-5D-5L) questionnaire. Utility values were estimated as preference measures that the patients assigned to their overall health status. Results: This study was based on 252 patients with TRD. The mean utility value by health state was 0.41, 0.63, 0.80, and 0.90, for MDE, response, remission, and recovery, respectively. At baseline, 59% of patients had an MADRS score of at least 28. Their baseline average utility value was lower compared to the other patients (0.43 versus 0.58, p < 0.001). This significant difference persisted at the following visits. The rate of patients in MDEs having at least one hospitalisation for depression or other reasons than depression was generally higher than that in the other health states. Conclusion: This study documented patterns in healthcare resource consumption, quality of life, and other characteristics in patients with TRD, both globally and by health state and depression severity.

scholarly journals A Review of the Mechanism of Antagonism of N-methyl-D-aspartate Receptor by Ketamine in Treatment-resistant Depression

Cureus ◽  
2018 ◽  
Author(s):  
Yasar Sattar ◽  
John Wilson ◽  
Ali M Khan ◽  
Mahwish Adnan ◽  
Daniel Azzopardi Larios ◽  
...  
Keyword(s):  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Aspartate Receptor ◽  
Resistant Depression
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