Ketamine Research

Efficacy for Depression

Electroconvulsive therapy (ECT) and subanesthetic intravenous ketamine are both currently used for treatment-resistant major depression, but the comparative effectiveness of the two treatments remains uncertain.

The authors tested whether an automated, computer-based approach could efficiently leverage enhanced neuroplasticity to extend the durability of rapid clinical response with intravenous ketamine.

A study was conducted to discover the pharmacodynamic actions of ketamine in depressed patients using EEG measures. The goal was to assess changes in symptoms and see whether repeated infusions could predict treatment response.

Electroconvulsive therapy (ECT) and subanesthetic intravenous ketamine are both currently used for treatment-resistant major depression, but the comparative effectiveness of the two treatments remains uncertain.

Intravenous (IV) ketamine is an effective therapy for treatment-resistant depression. A large data base is confirmatory and steadily expanding. Qualitative studies can inform best practices and suggest new research directions. As part of a clinical trial designed to identify biomarkers of ketamine response, a qualitative study was conducted to characterize experiences with: receiving infusions; recovering or not recovering from depression; and beliefs about why ketamine worked or did not work.

June 25, 2021

The use of ketamine for depression has increased rapidly in the past decades. Ketamine is often prescribed as an add-on to other drugs used in psychiatric patients, but clear information on drug-drug interactions is lacking. With this review, we aim to provide an overview of the pharmacodynamic interactions between ketamine and mood stabilizers, benzodiazepines, monoamine oxidase-inhibitors, antipsychotics, and psychostimulants.

November 30, 2021

Bipolar disorder (BD) is a recurrent condition with fluctuating mood swings from energetic mania/hypomania to severe depression, leading to significant disability and a high risk of mortality. Patients with BD spend most of their time in depressive episodes compared with manic or hypomanic episodes.

September 12, 2022

Few studies have been published to date exploring the effectiveness of ketamine for treatment-resistant depression (TRD) in large clinical samples. We report on the clinical outcomes of a large cohort treated with ketamine as part of clinical practice.

November, 2022

Ketamine has rapid yet often transient antidepressant effects in patients with treatment-resistant depression. Different strategies have been proposed to prolong these effects. Maintenance ketamine treatment appears promising, but little is known about its efficacy, safety, and tolerability in depression.

December 20, 2021

We are posting this article because it supports our observation that some patients who struggle with treatment-resistant depression and seek alternative treatments such as TMS and ketamine may have a bipolar-spectrum illness rather than major depression. It is a reminder that every patient who presents to TMS and ketamine providers with treatment-resistant depression should be properly screened for bipolar disorder. If a careful history reveals that a diagnosis of bipolar disorder is appropriate, then treatment recommendations such as the addition of mood stabilizers and second-generation antipsychotics, and discontinuation of traditional antidepressants should be considered.

January 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.

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.

July 13, 2020

Anorexia nervosa (AN) is a severe, biological brain disorder with significant medical risks and a tenacious development over time. Unfortunately, few treatments show efficacy in people with AN although numerous therapies including pharmacological have been explored.

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.

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.

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).

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 depressionresearch in the past half-century.

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.

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.

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,, and Scopus for relevant literature and bibliographies that included terms such as major depressive disorder, depression, bipolar disorder, remission.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

As a Maintenance Treatment

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.


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.

Ketamine for Depression in Adolescents

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.

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.”

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.

Efficacy of Ketamine for PTSD

April 20, 2022

Repeated ketamine infusions over 2 weeks were associated with large-magnitude improvement in post-traumatic stress disorder (PTSD) symptoms compared with a psychoactive placebo in individuals with chronic PTSD. Researchers published their findings in The American Journal of Psychiatry.

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.

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.

Ketamine for OCD

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.

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.

Ketamine with TMS

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.

Efficacy of Ketamine for Suicide Prevention

February 2, 2022

Objective: To confirm the rapid onset anti-suicidal benefits of ketamine in the short term and at six weeks, overall and according to diagnostic group.

Design: Prospective, double blind, superiority, randomised placebo controlled trial.

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.

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.


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

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.

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.

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.

Ketamine for Substance Abuse

January 26, 2022

Three weekly infusions of the dissociative anesthetic ketamine coupled with mindfulness-based relapse prevention therapy may help adults with alcohol use disorder (AUD) maintain abstinence, new research suggests.

January 11, 2022

Early evidence suggests that ketamine may be an effective treatment to sustain abstinence from alcohol. The authors investigated the safety and efficacy of ketamine compared with placebo in increasing abstinence in patients with alcohol use disorder. An additional aim was to pilot ketamine combined with mindfulness-based relapse prevention therapy compared with ketamine and alcohol education as a therapy control.

June 24, 2019

contentResearch 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.

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.

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.

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).

Ketamine for Anxiety

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.

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.

Neurogenerative Effects of Ketamine

April 11, 2019

NIH-supported study sheds light on the neural mechanisms underlying remission of depression

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.

Ketamine for Chronic Pain

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.

Ketamine Drug Properties and Mechanisms

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.

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.

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.

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.

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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