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 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 Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial

2018 ◽  
Vol 49 (4) ◽  
pp. 655-663 ◽  
Author(s):  
Fernanda Palhano-Fontes ◽  
Dayanna Barreto ◽  
Heloisa Onias ◽  
Katia C. Andrade ◽  
Morgana M. Novaes ◽  
...  
Keyword(s):  
Rating Scale ◽  
Remission Rate ◽  
Controlled Trial ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Open Label ◽  
Double Blind ◽  
Therapeutic Value ◽  
Antidepressant Effects ◽  
Resistant Depression

AbstractBackgroundRecent open-label trials show that psychedelics, such as ayahuasca, hold promise as fast-onset antidepressants in treatment-resistant depression.MethodsTo test the antidepressant effects of ayahuasca, we conducted a parallel-arm, double-blind randomized placebo-controlled trial in 29 patients with treatment-resistant depression. Patients received a single dose of either ayahuasca or placebo. We assessed changes in depression severity with the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Hamilton Depression Rating scale at baseline, and at 1 (D1), 2 (D2), and 7 (D7) days after dosing.ResultsWe observed significant antidepressant effects of ayahuasca when compared with placebo at all-time points. MADRS scores were significantly lower in the ayahuasca group compared with placebo at D1 and D2 (p= 0.04), and at D7 (p< 0.0001). Between-group effect sizes increased from D1 to D7 (D1: Cohen'sd= 0.84; D2: Cohen'sd= 0.84; D7: Cohen'sd= 1.49). Response rates were high for both groups at D1 and D2, and significantly higher in the ayahuasca group at D7 (64%v.27%;p= 0.04). Remission rate showed a trend toward significance at D7 (36%v.7%,p= 0.054).ConclusionsTo our knowledge, this is the first controlled trial to test a psychedelic substance in treatment-resistant depression. Overall, this study brings new evidence supporting the safety and therapeutic value of ayahuasca, dosed within an appropriate setting, to help treat depression. This study is registered athttp://clinicaltrials.gov(NCT02914769).

scholarly journals Sevoflurane augmentation in treatment-resistant depression: a clinical case study

2020 ◽  
Vol 10 ◽  
pp. 204512532095712
Author(s):  
Shikai Wang ◽  
Shanfei Cheng ◽  
Min Feng ◽  
Ping Guo ◽  
Mincai Qian ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Clinical Case ◽  
Efficacy And Safety ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Clinical Case Study ◽  
Antidepressant Effects ◽  
Mucous Membranes ◽  
Resistant Depression

Compared with other inhaled anaesthetics, sevoflurane has a faster onset and offset, causes less irritation to the mucous membranes, and has a better safety profile. These characteristics warrant investigating the effect of sevoflurane in depression. In this Case Report, we describe that sevoflurane treatment was feasible and well tolerated by a patient with treatment-resistant depression (TRD). Sevoflurane had rapid and durable antidepressant effects, with few adverse effects. Moreover, the patient showed significant improvements in neurocognitive measurements. Our preliminary results suggest that further clinical trials are needed to determine the independent efficacy and safety of sevoflurane in patients with TRD.

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.

S160. Antidepressant Effects of Single and Repeated Ketamine Infusions in Treatment-Resistant Depression

2018 ◽  
Vol 83 (9) ◽  
pp. S410 ◽  
Author(s):  
Jennifer Phillips ◽  
Sandhaya Norris ◽  
Jeanne Talbot ◽  
Abigail Ortiz ◽  
Meagan Birmingham ◽  
...  
Keyword(s):  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Antidepressant Effects ◽  
Resistant Depression

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 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 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.

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