Ketamine Research

Efficacy of Ketamine for Depression

Prolonged ketamine infusion modulates limbic connectivity and induces sustained remission of treatment-resistant depression

Jan 22, 2021
Ketamine produces a rapid antidepressant response in over 50% of adults with treatment-resistant depression. A long infusion of ketamine may provide durable remission of depressive symptoms, but the safety, efficacy, and neurobiological correlates are unknown. In this open-label, proof-of-principle study, adults with treatment-resistant depression (N = 23) underwent a 96-h infusion of intravenous ketamine (0.15 mg/kg/h titrated toward 0.6 mg/kg/h). Clonidine was co-administered to reduce psychotomimetic effects.

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Early symptomatic improvements as a predictor of response to repeated-dose intravenous ketamine: Results from the Canadian Rapid Treatment Center of Excellence

October 5, 2020
Early symptomatic improvement with monoamine-based antidepressants is predictive of treatment response. The objective of this study was to determine if early symptomatic improvements with intravenous (IV) ketamine predicted treatment response to an acute course of four infusions.

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Modulation of the antidepressant effects of ketamine by the mTORC1 inhibitor rapamycin

February 24, 2020
Twenty-four hours after administration, ketamine exerts rapid and robust antidepressant effects that are thought to be mediated by activation of the mechanistic target of rapamycin complex 1 (mTORC1). To test this hypothesis, depressed patients were pretreated with rapamycin, an mTORC1 inhibitor, prior to receiving ketamine.

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Antidepressant and neurocognitive effects of serial ketamine administration versus ECT in depressed patients

January 16, 2020
While electroconvulsive therapy (ECT) is considered the gold standard for acute treatment of patients with otherwise treatment-resistant depression, ketamine has recently emerged as a fast-acting treatment alternative for these patients. Efficacy and onset of action are currently among the main factors that influence clinical decision making, however, the effect of these treatments on cognitive functions should also be a crucial point, given that cognitive impairment in depression is strongly related to disease burden and functional recovery. ECT is known to induce transient cognitive impairment, while little is known about ketamine's impact on cognition. This study therefore aims to compare ECT and serial ketamine administration not only with regard to their antidepressant efficacy but also to acute neurocognitive effects.

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Double-blind, placebo-controlled, dose-ranging trial of intravenous ketamine as adjunctive therapy in treatment-resistant depression (TRD)

October 3, 2018
Numerous placebo-controlled studies have demonstrated the ability of ketamine, an NMDA receptor antagonist, to induce rapid (within hours), transient antidepressant effects when administered intravenously (IV) at subanesthetic doses (0.5 mg/kg over 40 min). However, the optimal antidepressant dose remains unknown. We aimed to compare to active placebo the rapid acting antidepressant properties of a broad range of subanesthetic doses of IV ketamine among outpatients with treatment-resistant depression (TRD).

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Ketamine A 'Lifesaving' Aid for Depression?

August 21, 2018
Ketamine, a widely used anesthetic that’s also an illicit party drug, has taken on a new role in recent years: treating severe depression in people who have not responded to standard treatment. Researchers have called it the most exciting breakthrough in the field of depression research in the past half-century.

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Low-Dose Ketamine Benefits Cognitive Function in Treatment-Resistant Depression

August 21, 2018
A low dose of ketamine infusion can provide a rapid and sustained antidepressant effect in patients with treatment-resistant depression, according to a study published in the Journal of Affective Disorders. In addition, a subanesthetic dose of ketamine was shown to improve functional impairment traditionally associated with treatment-resistant depression.

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Maintenance Ketamine Therapy for Treatment-Resistant Depression

August, 2018
Previous studies have demonstrated ketamine to have a rapid antidepressant effect in some patients with treatment-resistant depression (TRD), but the effect is unfortunately not sustained in the long term. In this study, we report on the clinical use of ongoing maintenance ketamine infusions in a group of patients with TRD, beyond an acute course of 6 to 8 ketamine infusions.

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Specific Features in Mood Disorders May Affect Outcome of Ketamine Treatment

May 12, 2018
Results of a recent study indicate that response to ketamine treatment in mood disorders may be better predicted based on existing baseline metabolic-inflammatory alterations, most notably cognitive impairment.

Researchers aimed to identify mood disorder subpopulations that were more, or less, likely to respond to treatment with ketamine. Current literature indicates that ketamine has a quick antidepressant effect on treatment-resistant depression symptoms in patients with both major depressive disorder (MDD) and bipolar disorder. The authors focused their study on predictive pretreatment elements in these disorders.

They searched PubMed/MEDLINE, ClinicalTrials.gov, and Scopus for relevant literature and bibliographies that included terms such as major depressive disorder, depression, bipolar disorder, remission.

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Features of Dissociation Differentially Predict Antidepressant Response to Ketamine in Treatment-Resistant Depression

February 17, 2018
Ketamine induces rapid and robust antidepressant effects, and many patients also describe dissociation, which is associated with antidepressant response. This follow-up study investigated whether antidepressant efficacy is uniquely related to dissociative symptom clusters.

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Ketamine and Depression: Is It Ready for Primetime?

February, 2018
Depression is common in the hospice and palliative care population,withprevalence estimates ranging from 17% in the palliative care population to up to 40% in hospice patients. Depressive disorders such as major depression frequently go unrecognized or undertreated, and are associated with significant disability, impaired quality of life, and increased healthcare utilization.

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Low-dose ketamine for treatment resistant depression in an academic clinical practice setting

January, 2017
Recent studies demonstrating a rapid, robust improvement in treatment resistant depression (TRD) following a single sub-anesthetic infusion of ketamine have generated much excitement. However, these studies are limited in their generalizability to the broader TRD population due to their subject exclusion criteria which typically limit psychiatric comorbidity, concurrent medication, and level of suicide risk. This paper describes the safety and efficacy of sub-anesthetic ketamine infusions in a naturalistic TRD patient sample participating in a real-world TRD treatment program within a major university health system.

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Ketamine for Depression: An Update

September 15, 2016
A decade has now passed since research into the antidepressant effects of ketamine began in earnest, after the clinical trial reported by Zarate et al. in 2006 (1). In that proof-of-concept study, 18 medication-free patients with treatment-resistant major depressive disorder (TRD) showed a large reduction in core depressive symptoms within hours of receiving a single low-dose 0.5 mg/kg intravenous infusion of ketamine as measured by the 21-item Hamilton Depression Rating Scale compared with saline placebo.

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Restoring Mood Balance in Depression: Ketamine Reverses Deficit in Dopamine-Dependent Synaptic Plasticity

April 2014
One of the most novel and exciting findings in major depressive disorder research over the last decade is the discovery of the fast-acting and long-lasting antidepressant effects of ketamine. Indeed, the therapeutic effects of classic antidepressants, such as selective serotonin reuptake inhibitors, require a month or longer to be expressed, with about a third of major depressive disorder patients resistant to treatment. Clinical studies have shown that a low dose of ketamine exhibits fast-acting relatively sustained antidepressant action, even in treatment-resistant patients. However, the mechanisms of ketamine action at a systems level remain unclear.

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A Double-Blind, Randomized, Placebo-Controlled, Dose-Frequency Study of Intravenous Ketamine in Patients With Treatment-Resistant Depression

April 2016
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 of ketamine in sustaining initial antidepressant effects in patients with treatment-resistant depression.

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Ketamine Safety and Tolerability in Clinical Trials for Treatment-Resistant Depression

March 2015
Ketamine has demonstrated rapid antidepressant effects in patients with treatment-resistant depression (TRD); however, the safety and tolerability of ketamine in this population have not been fully described. Herein we report the largest study to date of the safety, tolerability, and acceptability of ketamine in TRD.

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Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial

October 2013
Ketamine, a glutamate Nmethyl-D-aspartate (NMDA) receptor antagonist, has shown rapid antidepressant effects, but small study groups and inadequate control conditions in prior studies have precluded a definitive conclusion. The authors evaluated the rapid antidepressant efficacy of ketamine in a large group of patients with treatment-resistant major depression.

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Ketamine for Treatment-Resistant Depression: Ready or Not for Clinical Use?

October 2013
Treatment-resistant depression is a significant clinical problem with great morbidity and mortality (1). The report by Murrough et al. (2), published concurrently with this editorial, of their two-site randomized controlled clinical trial of ketamine in patients with treatment-resistant depression is an exciting and important step in evaluating a new and promising approach for these patients. Should our desire as clinicians to help these often desperate patients propel us to adopt ketamine now, or do we need to know more before proceeding? More studies, or change practice now? Let’s take a look.

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Rapid and Longer-Term Antidepressant Effects of Repeated Ketamine Infusions in Treatment-Resistant Major Depression

June 2012
Ketamine is reported to have rapid antidepressant effects; however, there is limited understanding of the time-course of ketamine effects beyond a single infusion. A previous report including 10 participants with treatment-resistant major depression (TRD) found that six ketamine infusions resulted in a sustained antidepressant effect. In the current report, we examined the pattern and durability of antidepressant effects of repeated ketamine infusions in a larger sample, inclusive of the original.

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Ketamine as a Maintenance Treatment

Maintenance Ketamine Treatment Produces Long-term Recovery from Depression

April 2010
Patients not responding to conventional treatment for depression are classified as having treatment-resistant depression (TRD). Electroconvulsive therapy is effective in ~50% of the patients diagnosed with TRD. Recent reports of rapid antidepressant effect with a single dose of ketamine suggest a potential benefit for TRD patients. However, there are no studies characterizing optimal dosing parameters (eg, frequency and inter-dose interval). The following case describes the effects of two ketamine administration regimens in a patient with a 15-year history of depression.

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Safety and Efficacy of Repeated-Dose Intravenous Ketamine for Treatment-Resistant Depression

2010
A single subanesthetic (intravenous) IV dose of ketamine might have rapid but transient antidepressant effects in patients with treatment-resistant depression (TRD). Here we tested the tolerability, safety, and efficacy of repeated-dose open-label IV ketamine (six infusions over 12 days) in 10 medication-free symptomatic patients with TRD who had previously shown a meaningful antidepressant response to a single dose.

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Ketamine for Depression in Adolescents

Ketamine shows potential in teens with treatment-resistant depression

August 14, 2018
Average scores on the Children's Depression Rating Scale dropped by 42.5% following low-dose IV ketamine infusions among 13 teenagers with treatment-resistant depression, findings published in Journal of Child and Adolescent Psychopharmacology showed.

“Adult [treatment-resistant depression] research has begun to explore repeated administrations of ketamine, which may have promise for greater effectiveness and longer remission periods than single doses,” Kathryn R. Cullen, MD, division of child and adolescent psychiatry, University of Minnesota Medical School, and colleagues wrote.

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Ketamine Eases Depression in Adolescents in Small Trial

August 8, 2018
Adolescents treated with intravenous ketamine for treatment-resistant depression showed a significant average decrease— 42.5%—in Children’s Depression Rating Scale scores, according to a small, open-label study published online in the Journal of Child and Adolescent Psychopharmacology.

“Novel interventions for treatment-resistant depression (TRD) in adolescents are urgently needed,” wrote researchers. “Ketamine has been studied in adults with TRD, but little information is available for adolescents.”

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Ketamine has potential therapeutic role in adolescents with treatment-resistant depression

August 1, 2018
A new study has shown a significant average decrease in the Children's Depression Rating Scale (42.5%) among adolescents with treatment-resistant depression (TRD) who were treated with intravenous ketamine. The study, which demonstrated the tolerability and potential role of ketamine as a treatment option for adolescents with TRD, is published in Journal of Child and Adolescent Psychopharmacology.

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Efficacy of Ketamine for PTSD

A Randomized Controlled Trial of Repeated Ketamine Administration for Chronic Posttraumatic Stress Disorder

Jan 5, 2021
Posttraumatic stress disorder (PTSD) is a chronic and disabling disorder, for which available pharmacotherapies have limited efficacy. The authors’ previous proof-of-concept randomized controlled trial of single-dose intravenous ketamine infusion in individuals with PTSD showed significant and rapid PTSD symptom reduction 24 hours postinfusion. The present study is the first randomized controlled trial to test the efficacy and safety of repeated intravenous ketamine infusions for the treatment of chronic PTSD.

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Efficacy of Intravenous Ketamine for Treatment of Chronic Posttraumatic Stress Disorder

April 2014
The primary outcome measure was change in PTSD symptom severity, measured using the Impact of Event Scale–Revised. Secondary outcome measures included the Montgomery-Asberg Depression Rating Scale, the Clinical Global Impression–Severity and –Improvement scales, and adverse effect measures, including the Clinician-Administered Dissociative States Scale, the Brief Psychiatric Rating Scale, and the Young Mania Rating Scale.

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Ketamine for OCD

Ketamine induces immediate and delayed alterations of OCD-like behavior.

January 11, 2020
Here, we aimed to provide a platform for investigating mechanisms underlying anti-OCD effects of ketamine treatment by assessing whether ketamine pretreatment could alleviate 5-HT1B receptor (5-HT1BR)-induced OCD-like behavior in mice.

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Randomized controlled crossover trial of ketamine in obsessive-compulsive disorder: proof-of-concept

November 2013
Serotonin reuptake inhibitors (SRIs), the first-line pharmacological treatment for obsessive-compulsive disorder (OCD), have two limitations: incomplete symptom relief and 2-3 months lag time before clinically meaningful improvement. New medications with faster onset are needed. As converging evidence suggests a role for the glutamate system in the pathophysiology of OCD, we tested whether a single dose of ketamine, a non-competitive N-methyl-D-aspartate (NMDA) glutamate receptor antagonist, could achieve rapid anti-obsessional effects.

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Ketamine with TMS

Combination therapy with transcranial magnetic stimulation and ketamine for treatment-resistant depression: A long-term retrospective review of clinical use

August 9, 2019
Both transcranial magnetic stimulation (TMS) and infused ketamine are recognized treatments for patients suffering from major depressive disorder (MDD). A novel therapy named combination TMS with ketamine (CTK) is introduced. This retrospective review examined the safety and clinical benefits of CTK in patients suffering from treatment-resistant depression (TRD) during the routine practice of psychiatry in a private clinic.

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Efficacy of Ketamine for Suicide Prevention

Ketamine for suicidal ideation in adults with psychiatric disorders: A systematic review and meta-analysis of treatment trials

November 15, 2019
Ketamine may reduce suicidal ideation in treatment-resistant depression. But it is not known how quickly this occurs and how long it persists. We undertook a systematic review and meta-analysis to determine the short- and long-term effectiveness of ketamine for suicidality.

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Ketamine Infusions Reduce Suicidal Ideation in Depression: Characterizing Different Responses

September 18, 2018
Ketamine infusions elicit different responses among 3 distinct subgroups of individuals dealing with depression and suicidal ideation. One group, remitters, had no suicidal ideation by day 2, and another group, responders, showed improvement independent of depressed mood, according to a study published in the Journal of Affective Disorders.

Researchers pooled data from 5 clinical trials involving treatment-resistant individuals with major depressive disorder or bipolar depression (N=128). All participants received a ketamine infusion and were evaluated at baseline and days 1 through 3. Evaluations included plasma markers to monitor neurotrophic factors, kynurenine pathway analytes, inflammatory cytokines, cortisol, and suicidal ideation composite scores to monitor depressed mood, hopelessness, sadness, and suicidal thoughts.

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Effects of Ketamine on Explicit and Implicit Suicidal Cognition: A Randomized Controlled Trial in Treatment-Resistant Depression

2014
Preliminary evidence suggests intravenous ketamine has rapid effects on suicidal cognition, making it an attractive candidate for depressed patients at imminent risk of suicide. In the first randomized controlled trial of ketamine using an anesthetic control condition, we tested ketamine’s acute effects on explicit suicidal cognition and a performance-based index of implicit suicidal cognition (Implicit Association Test; IAT) previously linked to suicidal behavior

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Ketamine for Bipolar Depression

A Systematic Review on the Efficacy of Intravenous Racemic Ketamine for Bipolar Depression

Jan/Feb, 2021
Ketamine, a glutamate N-methyl-d-aspartate receptor antagonist, has shown rapid antidepressant effects in treatment-resistant depression. We conducted a systematic review of studies evaluating the efficacy of intravenous ketamine augmentation in treatment-resistant depression patients with bipolar disorder.

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Safety and Tolerability of Ketamine Use in Treatment-Resistant Bipolar Depression Patients with Regard to Central Nervous System Symptomatology: Literature Review and Analysis

February 9, 2020
The current psychopharmacological treatment approaches for major depression focus on monoaminergic interventions, which are ineffective in a large proportion of patients. Globally, treatment-resistant bipolar depression (TRBD) affects up to 33% of depressive patients receiving treatment. Certain needs are still unmet and require new approaches.

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A Randomized Add-on Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Bipolar Depression

August 2010
—Existing therapies for bipolar depression have a considerable lag of onset of action. Pharmacological strategies that produce rapid antidepressant effects—for instance, within a few hours or days—would have an enormous impact on patient care and public health.

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Ketamine for Substance Abuse

A Single Ketamine Infusion Combined With Mindfulness-Based Behavioral Modification to Treat Cocaine Dependence: A Randomized Clinical Trial

June 24, 2019
Research has suggested that subanesthetic doses of ketamine may work to improve cocaine-related vulnerabilities and facilitate efforts at behavioral modification. The purpose of this trial was to test whether a single ketamine infusion improved treatment outcomes in cocaine-dependent adults engaged in mindfulness-based relapse prevention.

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Dual studies highlight ketamine’s potential to treat anxiety and addiction

January 10, 2019
Two new studies suggest the psychiatric benefits of ketamine treatment may extend beyond just the targeting of depression. The research demonstrates ketamine may be helpful in targeting both anxiety- and substance abuse-related depression.

Although ketamine is a relatively old drug, originally developed in the 1950s as an anesthetic, over the last decade a growing body of research has affirmed its unique, and rapid, antidepressant effects. The anecdotal effects of the drug on depression have raced ahead of scientific research so quickly that ketamine clinics have popped up all across the United States, where the drug can be administered for up to US$1,000 a dose.

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Efficacy of Ketamine in the Treatment of Substance Use Disorders: A Systematic Review

July 24, 2018
Despite advances in behavioral and pharmacotherapy interventions, substance use disorders (SUDs) are frequently refractory to treatment. Glutamatergic dysregulation has received increasing attention as one common neuropathology across multiple substances of abuse. Ketamine is a potent N-methyl-D-aspartate (NMDA) glutamatergic receptor antagonist which has been found to be effective in the treatment of severe depression.

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Ketamine psychotherapy for heroin addiction: immediate effects and two-year follow-up

May, 2002
Seventy detoxified heroin-addicted patients were randomly assigned to one of two groups receiving ketamine psychotherapy (KPT) involving two different doses of ketamine. The patients of the experimental group received existentially oriented psychotherapy in combination with a hallucinogenic (‘‘psychedelic’’) dose of ketamine (2.0 mg/kg im).

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Ketamine for Anxiety

Efficacy and safety of ketamine in the management of anxiety and anxiety spectrum disorders: a review of the literature

July 24, 2019
Anxiety disorders are among the most prevalent psychiatric conditions. Despite many proven pharmacological and non-pharmacological treatments available, high rates of partial response and low rates of long-term remission remain. Ketamine has been receiving increasing attention as an interventional treatment modality in psychiatry, especially among refractory conditions, including major depressive disorder.

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Dual studies highlight ketamine’s potential to treat anxiety and addiction

January 10, 2019
Two new studies suggest the psychiatric benefits of ketamine treatment may extend beyond just the targeting of depression. The research demonstrates ketamine may be helpful in targeting both anxiety- and substance abuse-related depression.

Although ketamine is a relatively old drug, originally developed in the 1950s as an anesthetic, over the last decade a growing body of research has affirmed its unique, and rapid, antidepressant effects. The anecdotal effects of the drug on depression have raced ahead of scientific research so quickly that ketamine clinics have popped up all across the United States, where the drug can be administered for up to US$1,000 a dose.

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Neurogenerative Effects of Ketamine

Ketamine Reverses Neural Changes Underlying Depression-Related Behaviors in Mice

April 11, 2019
NIH-supported study sheds light on the neural mechanisms underlying remission of depression

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Do antidepressants restore lost synapses?

April 12, 2019
Depression is a mental illness characterized by episodes of a sad, despondent mood and/or a loss of interest or pleasure (1). This pathology affects nearly 20% of the population in the United States (2), and treatments are limited. Indeed, in the 5 years following remission, 80% of patients will endure relapse and more than 30% of patients suffer from treatment-resistant depression. Recently, the U.S. Food and Drug Administration (FDA) approved the clinical use of esketamine nasal spray for depression that is resistant to other treatments (3). Esketamine is an enantiomer of ketamine, a drug with antidepressant properties, although its mechanism of action remains unclear. Brain imaging studies suggest that neuronal circuitry in the medial prefrontal cortex (mPFC) is involved in the physiopathology of this disorder (4). On page 147 of this issue, Moda-Sava et al. (5) report that ketamine induces plasticity of dendritic spines on mPFC neurons and restores microcircuit activity and behavior in animal models of depression. This may expand therapeutic strategies for treating major depression.

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Ketamine for Chronic Pain

Reduction of central neuropathic pain with ketamine infusion in a patient with Ehlers–Danlos syndrome: a case report

September 15, 2016
Ehlers–Danlos syndrome frequently causes acute and chronic pain because of joint subluxations and dislocations secondary to hypermobility. Current treatments for pain related to Ehlers–Danlos syndrome and central pain syndrome are inadequate. This case report discusses the therapeutic use of ketamine intravenous infusion as an alternative.

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Ketamine Drug Properties and Mechanism

Electrophysiological biomarkers of antidepressant response to ketamine in treatment-resistant depression: Gamma power and long-term potentiation.

January 17, 2020
Over the last two decades, the discovery of ketamine's antidepressant properties has galvanized research into the neurobiology of treatment-resistant depression. Nevertheless, the mechanism of action underlying antidepressant response to ketamine remains unclear. This study reviews electrophysiological studies of ketamine's effects in individuals with depression as well as healthy controls, with a focus on two putative markers of synaptic potentiation: gamma oscillations and long-term potentiation.

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Ketamine normalizes subgenual cingulate cortex hyper-activity in depression

January 2, 2020
Mounting evidence supports the rapid antidepressant efficacy of the N-methyl-D-aspartate receptor antagonist, ketamine, for treating major depressive disorder (MDD); however, its neural mechanism of action remains poorly understood.

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Leveraging Neuroplasticity to Enhance Adaptive Learning: The Potential for Synergistic Somatic-Behavioral Treatment Combinations to Improve Clinical Outcomes in Depression

March 15, 2019
Until recently, therapeutic development in psychiatry was targeted solely toward symptom reduction. While this is a worthwhile goal, it has yielded little progress in improved therapeutics in the last several decades in the field of mood disorders.

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Synaptic Dysfunction in Depression: Potential Therapeutic Targets

October 2012
Basic and clinical studies demonstrate that depression is associated with reduced size of brain regions that regulate mood and cognition, including the prefrontal cortex and the hippocampus, and decreased neuronal synapses in these areas. Antidepressants can block or reverse these neuronal deficits, although typical antidepressants have limited efficacy and delayed response times of weeks to months.

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NMDA Receptor Blockade at Rest Triggers Rapid Behavioural Antidepressant Responses

July 2011
Clinical studies consistently demonstrate that a single sub-psychomimetic dose of ketamine, an ionotropic glutamatergic NMDAR (N-methyl-D-aspartate receptor) antagonist, produces fast-acting antidepressant responses in patients suffering from major depressive disorder, although the underlying mechanism is unclear.

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