December 28, 2017V. Whizar-Lugo, Cesar Heredia-Mota, R. Camacho
Major depression (MD) is a very common chronic mental illness that causes substantial disability in millions of adolescents and adults throughout the world. In the United States of North America there is an annual risk of depression of 6.6%. Unfortunately, only 30-40% of patients will remit with the usual antidepressant drugs and there is a high risk of suicide attempts during the first month...
Importance: Approximately one-third of patients with major depressive disorder (MDD) do not respond to available antidepressants. Objective: To assess the efficacy, safety, and dose-response of intranasal esketamine hydrochloride in patients with treatment-resistant depression (TRD). Design, Setting, and Participants: This phase 2, double-blind, doubly randomized, delayed-start,...
Depression is a highly prevalent and severely disabling disease. The treatment effects, intensity and onset time of antidepressants have been highlighted in many studies. Recent studies on the rapid-onset of antidepressant response focused on the effect of a single low dose of intravenous ketamine. However, there are still some problems with treatment, including safety, efficacy, ethics, dose,...
Major depressive disorder (MDD) affects approximately 10% to 20% of the US population (Kessler et al. , 2005); thus, the economic burden of MDD is immense. Currently, selective serotonin reuptake inhibitors and serotonin- and noradrenaline-reuptake inhibitors are widely prescribed for patients with MDD as first-line treatments. However, these medications have several drawbacks; approximately...
Abstract Background We previously reported that serotonergic transmission plays an important role in antidepressant effects of ketamine. However, detailed mechanisms have not been elucidated. Among the serotonin receptor subtypes, the serotonin1A receptor in the medial prefrontal cortex has an important role in depression. Here, we investigated the role of the medial prefrontal cortex...
Objective To evaluate the antidepressant action of melatonin in stress model of depression and the effects of the melatonin on depressive-like behavior. Methods Forty male Wistar rats were randomly divided into four groups(n=10): controls group (CON), chronic unpredictable mild stress group(CUS), chronic unpredictable mild stress group + melatonin group(CUS+ MT) and chronic unpredictable mild...
Disrupted mental health affects up to one in three individuals globally and is an unmet medical challenge contributing to individual suffering as well as significant societal and economic burden [1...
Accumulating evidence suggests that the gut microbiota-brain axis plays a role in the pathogenesis of depression, thereby contributing to the antidepressant actions of certain compounds. (R)-ketamine has a greater potency and longer-lasting antidepressant effects than (S)-ketamine. Here, we investigated whether the gut microbiota plays a role in the antidepressant effects of these two ketamine...
Objective Pharmacotherapy to rapidly relieve suicidal ideation in depression may reduce suicide risk. Rapid reduction in suicidal thoughts after ketamine treatment has mostly been studied in patients with low levels of suicidal ideation. Method This randomized clinical trial tested the effect of adjunctive sub-anesthetic intravenous ketamine on clinically significant suicidal ideation in major...
December 1, 2017Tatiana M N Rezende, J. P. Maia-De-Oliveira, Ludmyla Kandratavicius et al.
Background: Recent evidence has shown improvements in schizophrenia symptoms after the infusion of sodium nitroprusside (SNP), a nitric oxide (NO) donor. In the rat model of schizophrenia using ketamine injection, pretreatment with SNP seems to prevent behavioral changes associated with positive symptoms for up to one week. Objective: We investigated whether SNP would have preventative effects...
Major depressive disorder (MDD) is one of the most prevalent psychiatric disorders. Until the recent discovery of the rapid onset antidepressant action of ketamine, pharmacological treatments for MDD were limited to conventional antidepressant drugs with delayed clinical efficacy. Using a judgement bias task, this study has investigated whether the temporal differences observed in patients...
The antidepressant effects of ketamine are thought to depend on brain-derived neurotrophic factor (BDNF) genotype and dose. The purpose of this study was to characterize the dose-related antidepressant effects of ketamine in patients with treatment-resistant depression drawn from a Chinese population predominately possessing lower activity BDNF genotypes (Val/Met, Met/Met). We conducted a...
Ketamine has been used as a pharmacological model for schizophrenia as subanesthetic infusions have been shown to produce temporary schizophrenia-like symptoms in healthy humans. More recently, ketamine has emerged as a potential treatment for multiple psychiatric disorders, including treatment-resistant depression and suicidal ideation. However, the mechanisms underlying both the...
There is a great unmet need for new medications with novel mechanisms of action that can effectively treat patients who do not benefit from standard antidepressant therapies. After a period in which it seemed as if the pharmaceutical pipeline for new antidepressants was going dry, the past decade has witnessed renewed interest, beginning with discovery of the antidepressant effects of ketamine....
Chronic ketamine use leads to cognitive and affective deficits including depression. Here, we examined sex differences and neural bases of depression in chronic ketamine users. Compared to non-drug using healthy controls (HC), ketamine-using females but not males showed increased depression score as assessed by the Center of Epidemiological Studies Depression Scale (CES-D). We evaluated resting...
Adult neurogenesis persists in the rodent dentate gyrus and is stimulated by chronic treatment with conventional antidepressants through BDNF/TrkB signaling. Ketamine in low doses produces both rapid and sustained antidepressant effects in patients. Previous studies have shed light on post-transcriptional synaptic NMDAR mediated mechanisms underlying the acute effect, but how ketamine acts at...
Low doses of ketamine trigger rapid and lasting antidepressant effects after one injection in treatment-resistant patients with major depressive disorder. Modulation of AMPA receptors (AMPARs) in the hippocampus and prefrontal cortex is suggested to mediate the antidepressant action of ketamine and of one of its metabolites (2R,6R)-hydroxynorketamine ((2R,6R)-HNK). We have examined whether...
Scientific ReportsNovember 17, 2017Katja Weckmann, Michael J Deery, Julie A Howard et al.
Fewer than 50% of all patients with major depressive disorder (MDD) treated with currently available antidepressants (ADs) show full remission. Moreover, about one third of the patients suffering from MDD does not respond to conventional ADs and develop treatment-resistant depression (TRD). Ketamine, a non-competitive, voltage-dependent N-Methyl-D-aspartate receptor (NMDAR) antagonist, has been...
The purpose of this paper is to provide a review of the use of ketamine as an antidepressant for treatment-resistant depression (TRD) in the geriatric population. Available treatment options for late-life treatment-resistant depression are limited and include electroconvulsive therapy and transcranial magnetic stimulation as well as possible pharmacologic augmentation. Ketamine has been shown...