Ketamine, major depressive disorder, treatment resistant

BACKGROUND: The N-methyl-D-aspartate antagonist ketamine has rapid onset antidepressant activity in treatment-resistant depression (TRD). AIMS: To evaluate mood rating, safety and tolerability data from patients with TRD treated with ketamine and the psychoactive control fentanyl, as part of a larger study to explore EEG biomarkers associated with mood response. METHODS: We evaluated the efficacy and safety of intramuscular racemic ketamine in 25 patients with TRD, using a double-blind active-controlled randomized crossover design...

Over the past six decades, the use of ketamine has evolved from an anesthetic and recreational drug to the first non-monoaminergic antidepressant approved for treatment-resistant major depressive disorder (MDD). Subanesthetic doses of ketamine and its enantiomer (S)-ketamine (esketamine) directly bind to several neurotransmitter receptors [including N-methyl-d-aspartic acid receptor (NMDAR), κ and μ opioid receptor (KOR and MOR)] widely distributed in the brain and across different cell types, implicating several potential molecular mechanisms underlying the action of ketamine as an antidepressant...

BACKGROUND: Sleep disturbances are highly prevalent in depressive episodes and are linked to higher mood severity and suicidal behaviors. Slow wave sleep (SWS) and REM sleep are compromised in depression. Current evidence suggests that rapid antidepressant effects of intravenous (IV) ketamine in patients with treatment-resistant depression (TRD) is mediated by its effects on SWS and REM sleep. Sleep phenotypes may help predict ketamine response. METHOD: In this observational study, we investigated differences in rates of response among sleep phenotypes defined by QIDS-SR in a cohort of patients with TRD (n = 52) treated with IV ketamine or intranasal (IN) esketamine...

OBJECTIVE: Converging evidence supports the role of the glutamate, an excitatory amino acid neurotransmitter, in the pathophysiology of obsessive-compulsive disorder (OCD). Ketamine and esketamine, both noncompetitive N-methyl-d-aspartate antagonists, have emerged as a promising medication for this psychiatric disorder, given its possible efficacy with faster onset and good tolerability. The purpose of this retrospective chart review is to evaluate whether unbiased clinical documentation supports formal clinical trials of esketamine for an OCD indication...

Objective: Ketamine has proved effective as a rapid-acting antidepressant agent, but treatment is not effective for everyone (approximately a quarter to a half of patients). Some adult studies have begun to investigate predictors of ketamine's antidepressant response, but no studies have examined this in adolescents with depression. Methods: We conducted a secondary data analysis of adolescents who participated in a randomized, single-dose, midazolam-controlled crossover trial of ketamine for adolescents with treatment-resistant depression...

Ketamine and its enantiomers represent an innovative glutamatergic agent as a treatment for individuals with treatment-resistant depression (TRD) and major depressive disorder (MDD) with suicidal ideation and behavior. Intranasal (IN) formulations could allow for quick onset of action on depressive symptoms as well as a reduction in side effects by bypassing the blood-brain barrier compared with administration via the intravenous route. The aim of this review was to provide an up-to-date analysis of the data on the efficacy and safety of IN ketamine and IN esketamine for the treatment of MDD...

BACKGROUND: Prior trials suggest that intravenous racemic ketamine is a highly effective for treatment-resistant depression (TRD), but phase 3 trials of racemic ketamine are needed. AIMS: To assess the acute efficacy and safety of a 4-week course of subcutaneous racemic ketamine in participants with TRD. Trial registration: ACTRN12616001096448 at www.anzctr.org.au. METHOD: This phase 3, double-blind, randomised, active-controlled multicentre trial was conducted at seven mood disorders centres in Australia and New Zealand...

Ketamine, a non-competitive antagonist of the N-methyl-D-aspartate-glutamate receptor (R-NMDA), has a rapid (from 24 h post-dose) and prolonged (up to one week) antidepressant effect in treatment resistant depression and in rodent models of anxiety/depression. Arguments regarding its cellular and molecular mechanisms underlying its antidepressant activity mainly come from animal studies. However, debates still persist on the structural remodeling of frontocortical/hippocampal neurons and the role of excitatory/inhibitory neurotransmitters involved in its behavioral effect...

Treatment-resistant depression (TRD) is a term used to describe a particular type of major depressive disorder (MDD). There is no consensus about what defines TRD, with various studies describing between 1 and 4 failures of antidepressant therapies, with or without electroconvulsive therapy (ECT). That is why TRD is such a growing concern among clinicians and researchers, and it explains the necessity for investigating novel therapeutic targets beyond conventional monoamine pathways. An imbalance between two primary central nervous system (CNS) neurotransmitters, L -glutamate and γ-aminobutyric acid (GABA), has emerged as having a key role in the pathophysiology of TRD...

Ketamine recently approved for therapy of treatment-resistant depression shows a complex and not fully understood mechanism of action. Apart from its classical glutamatergic N-methyl-D-aspartate receptor antagonistic action, it is thought that anti-inflammatory properties of the drug are of clinical relevance due to the contribution of activated inflammatory mediators to the pathophysiology of depression and non-responsiveness of a group of patients to current antidepressant therapies. In a search of the mechanism underlying anti-inflammatory effects of ketamine, the nuclear factor kappa B transcription factor (NF-κB) has been proposed as a target for ketamine...

Major Depressive Disorder (MDD) is a leading cause of disability worldwide. Conventional antidepressant treatment is characterised by a significant time to onset of therapeutic action (approximately 2 weeks) and fails to achieve a stable remission of symptoms in one-third of subjects with MDD. In the last 20 years the discovery of antidepressant effects of the N-methyl-d-aspartate (NMDA) receptor antagonist ketamine as a rapid acting (within hours) and sustained (up to 7 days) antidepressant has represented a major paradigm shift in the field...

Treatment-resistant depression (TRD) is a subgroup of major depressive disorder in which the use of classical antidepressant treatments fails to achieve satisfactory treatment results. Although there are various definitions and grading models for TRD, common criteria for assessing TRD have still not been established. However, a common feature of any TRD model is the lack of response to at least two attempts at antidepressant pharmacotherapy. The causes of TRD are not known; nevertheless, it is estimated that even 60% of TRD patients are so-called pseudo-TRD patients, in which multiple biological factors, e...

There has recently been a resurgence of interest in psychedelic compounds based on studies demonstrating their potential therapeutic applications in treating post-traumatic stress disorder, substance abuse disorders, and treatment-resistant depression. Despite promising efficacy observed in some clinical trials, the full range of biological effects and mechanism(s) of action of these compounds have yet to be fully established. Indeed, most studies to date have focused on assessing the psychological mechanisms of psychedelics, often neglecting the non-psychological modes of action...

BACKGROUND: The evidence base for racemic ketamine treatment for treatment-resistant major depressive disorder (TRD) continues to expand, but there are major challenges translating this evidence base into routine clinical care. AIM: To prepare guidelines for ketamine treatment of TRD that are suitable for routine use by publicly funded specialist mental health services. METHOD: We consulted with senior leadership, clinical pharmacy, psychiatrists, nursing, service users and Māori mental health workers on issues relating to ketamine treatment...

Migraine and major depressive disorders (MDD) or treatment resistant depression (TRD) represent a significant global burden and are often comorbid, further complicating diagnosis and treatment. Epidemiological studies have demonstrated a bidirectional relationship between migraine and MDD/TRD, with patients suffering from one disorder exhibiting a heightened risk of developing the other. This association is believed to result from shared genetic factors, neurotransmitter dysregulation, inflammation, hormonal alteration, and other conditions comorbid with both disorders...

Major depressive disorder (MDD) in children and adolescents is a significant health problem, causing profound impairments in social, academic, and family functioning and substantial morbidity and mortality. Up to 15% of children and adolescents suffer from MDD, and a proportion, around 30 to 40% of them, failed to respond to initial selective serotonin reuptake inhibitor (SSRI) treatment. The only evidence-based recommendation is medication switching to another SSRI and augmentation with cognitive behavioral therapy...

Major Depressive Disorder (MDD) is a highly debilitating disorder characterized by a persistent feeling of sadness and anhedonia. Traditional antidepressants have a delayed onset of action and lack of efficacy in up to one third of patients, leading to treatment resistant depression (TRD). Recent years have witnessed a revolutionary treatment of TRD with the introduction of the fast-acting antidepressant ketamine. However, ketamine's mechanisms of action are still poorly understood. Here, we used the chronic mild stress animal model of depression on male rats to investigate the involvement of neurotrophic signaling pathways in stress vulnerability/resilience and fast antidepressant response/non-response to acute subanesthetic ketamine...

Mental health disorders are among the most common health conditions in the United States. Traditional clinical treatments rely on psychiatric counseling and, in many cases, prescription medications. We propose an innovative model, Interventional Mental Health, which employs a combination of modalities through a multifaceted approach to treat conditions that have exhibited limited responsiveness to traditional methods and individuals afflicted with multiple comorbidities simultaneously. We hypothesize that creating a unique treatment algorithm combining current therapeutic modalities such as Stellate Ganglion Blocks (SGB), Transcranial Magnetic Stimulation (TMS) therapy, and ketamine therapy, within a consolidated timeframe, will yield synergistic outcomes among patients presenting with comorbid post-traumatic stress disorder (PTSD), depression, and/or anxiety...

BACKGROUND: Approximately one third of individuals with major depressive disorder have treatment-resistant depression (TRD). Glutamatergic modulators such as the N -methyl- d -aspartate receptor antagonist ketamine have rapid and robust antidepressant effects, but their use has been limited by accessibility and route of administration. This open-label pilot study assessed the adjunctive antidepressant efficacy of dextromethorphan/quinidine (DM/Q) in TRD. METHODS: Inpatients with TRD (n = 17, 40...

Concurrent with recent insights into the neuroprogressive nature of depression, ketamine shows promise in interfering with several neuroprogressive factors, and has been suggested to reverse neuropathological patterns seen in depression. These insights come at a time of great need for novel approaches, as prevalence is rising and current treatment options remain inadequate for a large number of people. The rapidly growing literature on ketamine's antidepressant potential has yielded multiple proposed mechanisms of action, many of which have implications for recently elucidated aspects of depressive pathology...