A retrospective chart review of an open-label trial of low-dose ketamine administered to front-line Healthcare workers who were identified as experiencing acute stress disorder due to the COVID-19 Pandemic.

We will conduct a crossover trial in which as many as 36 adolescents (18 with MDD and 18 with anxiety disorders) will be given a single infusion of ketamine (study drug) or midazolam (active control). MDD symptoms and anxiety symptoms will be monitored over a two-week period. If applicable, comorbid school refusal symptoms will also be monitored over a two-week period for both cohorts. A 2-week washout period will be required between infusion doses. Our primary outcomes will be 1) improvement in MDD symptoms (measured by Montgomery-Asberg Depression Rating Scale, revised (MADRS) score) 1 day after infusion, for the cohort of subjects enrolled in the MDD arm of this trial and 2) improvement in the anxiety symptoms (measured by the Multimodal Anxiety Scale for Children (MASC) acute physical symptoms subscale) for the cohort of subjects enrolled in the anxiety disorders arm of the trial.

Ketamine is the only clinician-prescribed psychedelic medicine available to mental health providers for the treatment of emotional suffering, and psychedelic experience is an inherent, valued, and well-tolerated part of the authors’ methodology. In this study, 235 patients across three practices received ketamine sublingually (both in-office and at home), intramuscularly, or both, along with psychotherapy. The data support the efficacy of ketamine-assisted psychotherapy for a wide variety of psychiatric diagnoses and human difficulties, significantly diminishing depression, anxiety, and PTSD and increasing well-being.

This study sought to evaluate the effect of weekly ketamine treatments for three months on anxiety ratings, safety and tolerability in patients with treatment-refractory generalised anxiety disorder (GAD) and/or social anxiety disorder (SAD), and subsequent assessment of remission post-treatment. Patients received one or two weekly ketamine doses of 1 mg/kg injected subcutaneously for 3 months. Patients reported marked improvements in functionality and in their personal lives. Maintenance ketamine may be a therapeutic alternative for patients with treatment refractory GAD/SAD.

Many patients with social anxiety disorder (SAD) experience inadequate symptom relief from available treatments. Ketamine is a potent N-methyl-d-aspartate receptor antagonist with a potentially novel mechanism of action for the treatment of anxiety disorders. This proof-of-concept trial provides initial evidence that ketamine may be effective in reducing anxiety.

The purpose of this study is to examine the effectiveness of a single infusion of ketamine (KET), to determine which dose is optimal 7 days after infusion using Bayesian Adaptive Randomization, and to learn about how ketamine works in the body and brain in persons with late-life treatment resistant depression.

NeuroRx is developing NRX-101, a fixed-dose combination oral capsule composed of d-cycloserine (DCS) and lurasidone for the maintenance of remission from Severe Bipolar Depression with Acute Suicidal Ideation (C-SSRS level 4 or 5) or Behavior (ASIB) in following initial stabilization. Patients with Severe Bipolar Depression and ASIB will be recruited in both inpatient and outpatient settings and, following informed consent, will be given an intravenous infusion of ketamine 0.5mg/kg over 40 minutes. Those who exhibit a satisfactory clinical response to ketamine will be randomly allocated to NRX-101 or to lurasidone alone (the comparator group). This study is conducted as a feasibility study for a pivotal phase 2b/3 clinical trial and the primary outcomes for this phase 2 study were blood levels of NRX-101, in order to confirm pharmaco-kinetics with remission from depression, as measured by BISS-derived MADRS and relapse as secondary outcomes.

Depression frequently emerges during adolescence and is associated with severe outcomes. Current interventions do not lead to remission for many adolescents. Treatment-resistant depression (TRD) in adolescence is an ominous prognostic indicator for a lifetime of suffering and increased risk for suicide. Efforts should be directed toward novel interventions that could alter this perilous course. Theoretically, restoration of healthy development during this critical window would substantially improve outcomes over the lifespan.

The primary goal of the project is to study the effect of Ketamine on cortical neurophysiological function in Treatment Resistant Depression(TRD) patients. There are three key preclinical findings regarding Ketamine antidepressant effects that motivate the current study: a) low dose Ketamine causes early increase in glutamate neurotransmission; b) Ketamine initiates synaptic plasticity; c) ketamine infusion leads to rapid improvement in depression symptoms. The proposal essentially employs robust and non-invasive neurophysiological techniques, Auditory Steady State Response(ASSR)-gamma oscillatory response and Transcranial Magnetic Stimulation(TMS) cortical excitability to investigate the above findings in patients with treatment resistant depression.

About one-third of depressed patients will not get better after multiple antidepressant treatments. This situation put a high burden on patients with depression due to worsening quality of life and increasing health care costs. Difficult-to-treat depression might be even worse among Veterans given that the frequency of depressive symptoms is 2 to 5 times higher than among the general US population. A breakthrough discovery happened in recent years when investigators found that one infusion from an old anesthetic named ketamine showed high efficacy and rapid antidepressant effect (sometimes within hours) but lasted only up to a week. The investigators propose to study if multiple infusions of ketamine can provide greater and longer antidepressant effects than one infusion. If that is the case, multiple infusions could be an alternative to relieve depressive symptoms that do not response to multiple antidepressant drugs.

Ketamine has been shown to decrease symptoms of anxious depression quickly. This decrease has been shown to last for up to one month. MRI technology will be used before and after ketamine for patients with depression to examine the extent to which certain brain areas predict ketamine's antidepressant effects.

This study aimed to assess the effectiveness of a broad range of subanesthetic IV ketamine doses in the acute (72 h) treatment of TRD patients, when added to stable antidepressant therapy. The results suggest that there is evidence for the antidepressant efficacy of the 0.5 mg/kg and 1.0 mg/kg subanesthetic doses of IV ketamine and no clear or consistent evidence for clinically meaningful efficacy of lower doses of IV ketamine.

Depressive disorders may be severe, chronic and often life-threatening illnesses. Impairment in physical and social functioning resulting from depression can be just as severe as other chronic medical illnesses. Recent preclinical and clinical studies suggest that the glutamatergic system is involved in the mechanism of action of antidepressants.

The purpose of this study is to test the antidepressant effect of ketamine when given repeatedly over a period of 1 week, as well as the use of Lithium as a relapse-prevention strategy for patients with treatment-resistant depression (TRD) who respond to an initial series of ketamine infusions. Ketamine is a Food and Drug Administration approved anesthetic (a drug used to produce loss of consciousness before and during surgery). Ketamine is not approved for the treatment of major depressive disorder and is considered experimental in this study. An additional purpose of this study is to research the effects of ketamine on brain function.

The primary objective is to investigate whether all doses (0.1 mg/kg, 0.2 mg/kg, 0.5 mg/kg, and 1.0 mg/kg) of ketamine are superior to active placebo (midazolam 0.045 mg/kg) therapy in the acute treatment of patients with treatment resistant depression within 72 hours (Day 3), when added to ongoing and stable antidepressant therapy.

This is a double-blind (patients and study personnel do not know the identity of the administered treatments), randomized (the drug is assigned by chance), placebo-controlled (placebo is a substance that appears identical to the treatment and has no active ingredients), parallel arm study (each group of patients will be treated at the same time). The study will consist of a screening phase of up to 4 weeks, a 4-week double-blind treatment phase (Day 1 to Day 29), and a 3-week post treatment (follow up) phase. In the double-blind phase, patients will receive over 4 weeks either intravenous (IV) infusions of placebo (2 or 3 times weekly) or IV infusions of ketamine (2 or 3 times weekly). The total study duration for each patient will be a maximum of 13 weeks.

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. 67 patients with treatment-resistant depression received intravenous ketamine (or placebo) either two or three times per week for up to four weeks. At day 15, MADRS (depression rating scale) scores were measured for both groups. The twice-weekly dosing groups saw a mean change of -18.4 (vs. -5.7 for placebo) and the thrice-weekly groups saw a mean change of -17.7 (vs. -3.1 for placebo), indicating similar antidepressant effects for both dose-frequencies.

This study is examining the safety and effectiveness of two medications, ketamine and riluzole, in treating patients with treatment resistant major depressive disorder. This study will also examine the effectiveness of an FDA approved drug called lamotrigine in decreasing the potential side effects associated with ketamine.

The relationship between depression and trauma is well established. Co-occuring depression and post-traumatic stress disorder (PTSD) are associated with more severe symptoms and lower levels of functioning. Veterans with both depression and PTSD have been shown to be at much higher risk of suicide than individuals with only one of these disorders. Ketamine has been shown to have rapid antidepressant effects and also therapeutic action over PTSD symptoms. The purpose of this study is to see whether ketamine, when given as repeated infusions, can produce quick and sustained improvement in depression and PTSD symptoms for individuals who have not had their symptoms effectively treated by current treatments.

Given the significant disability, morbidity and mortality associated with depression, the promising recent trials of ketamine highlight a novel intervention. A meta-analysis was conducted to assess the efficacy of ketamine in comparison with placebo for the reduction of depressive symptoms in patients who meet criteria for a major depressive episode. The large and statistically significant effect of ketamine on depressive symptoms supports a promising, new and effective pharmacotherapy with rapid onset, high efficacy and good tolerability.

Data from 108 treatment-resistant inpatients meeting criteria for major depressive disorder and bipolar disorder who received a single subanesthetic ketamine infusion were analyzed. Among the examined mediators of ketamine׳s antidepressant response, only dissociative side effects predicted a more robust and sustained antidepressant.

Accumulating evidence suggests that ketamine may exert rapid antidepressant effects in major depressive disorder patients. This study showed that ketamine is as effective as ECT in improving depressive symptoms in MDD patients and has more rapid antidepressant effects compared with the ECT.

Existing treatments for major depressive disorder (MDD) generally take weeks to months to exert their maximal benefit. There is an urgent need to develop rapid-acting treatments for MDD. Ketamine, a high-affinity N-methyl-D-aspartate (NMDA) glutamate receptor antagonist, has been used as a standard intravenous (IV) anesthetic agent for many years in both pediatric and adult patients. Beyond its well-established role in anesthesia and pain management, there is emerging evidence that ketamine may have rapid antidepressant properties for patients with severe mood disorders.

The authors evaluated the rapid antidepressant efficacy of ketamine in a large group of patients with treatment-resistant major depression. Ketamine demonstrated rapid antidepressant effects in an optimized study design, further supporting NMDA receptor modulation as a novel mechanism for accelerated improvement in severe and chronic forms of depression.

Very low dose sublingual ketamine (10 mg) was administered every 2-3 days or weekly to 26 out-patients with refractory unipolar or bipolar depression. Patients reported clear and sustained effects, improving mood level and stability, cognition, and sleep in 77% of patients, with only mild and transient light-headedness as a common side-effect. Remission remained in some patients after stopping ketamine.

As of May 21st, 2012, the purpose of this study is to test the antidepressant effect of ketamine when given repeatedly over a period of 1 week, as well as the use of Lithium as a relapse-prevention strategy for patients with treatment-resistant depression (TRD) who respond to an initial series of ketamine infusions. Ketamine is a Food and Drug Administration approved anesthetic (a drug used to produce loss of consciousness before and during surgery). Ketamine is not approved for the treatment of major depressive disorder and is considered experimental in this study.

Existing therapies for major depression have a lag of onset of action of several weeks, resulting in considerable morbidity. Pharmacological strategies that have rapid onset and sustained antidepressant effects would have an enormous impact on patient care. Converging lines of evidence suggest the role of the glutamatergic system in the pathophysiology and treatment of mood disorders. In this study, a single intravenous dose of ketamine resulted in robust and rapid antidepressant effects. Onset occurred within 2 hours postinfusion and continued to remain significant for 1 week.

This pilot study is proposed to determine the acceptability, feasibility and potential efficacy of ketamine, a medication that modulates glutamate in the brain, as a rapid treatment for obsessive-compulsive disorder (OCD) symptoms in adolescents and young adults with OCD. This study will recruit 6 youth (ages 14-22) who are diagnosed with clinically significant OCD and have failed at least one adequate trial of a Serotonin Reuptake Inhibitor (SRI) medication and a course of Cognitive-Behavioral Therapy (CBT) (unless unable to access or tolerate) for OCD in the past. Participants will receive a single infusion of intravenous ketamine and be assessed at regular intervals post-infusion for up to 14 days. At the end of the 14-day treatment phase, all participants will be offered three months of open treatment for OCD with medication and/or CBT.

This pilot study is proposed to determine the acceptability, feasibility and potential efficacy of ketamine, a medication that modulates glutamate in the brain, as a rapid treatment for obsessive-compulsive disorder (OCD) symptoms in adolescents and young adults with OCD. This study will recruit 6 youth (ages 14-22) who are diagnosed with clinically significant OCD and have failed at least one adequate trial of a Serotonin Reuptake Inhibitor (SRI) medication and a course of Cognitive-Behavioral Therapy (CBT) (unless unable to access or tolerate) for OCD in the past. Participants will receive a single infusion of intravenous ketamine and be assessed at regular intervals post-infusion for up to 14 days. At the end of the 14-day treatment phase, all participants will be offered three months of open treatment for OCD with medication and/or CBT.

Obsessive-compulsive disorder (OCD) is a common psychiatric illness that affects up to 2-3% of the population. People with OCD experience anxiety-provoking, intrusive thoughts, known as obsessions, and feel compelled to perform repetitive behaviors, or compulsions. The only medications proven effective for OCD are serotonin reuptake inhibitors (SRIs), but even with SRI treatment, most patients continue to experience significant OCD symptoms, impaired functioning, and diminished quality of life. Recent evidence suggest that a different neurotransmitter, glutamate, may contribute to the symptoms in OCD. Medications that target glutamate hold promise for ameliorating symptoms for those patients continuing to suffer from OCD. In this study the investigators are recruiting patients to receive the drug memantine, which is thought to modulate the neurotransmitter glutamate, added to whatever other OCD medications they are taking.

This study investigates if a single dose of IV Ketamine can rapidly improve Obsessive-Compulsive Disorder (OCD) symptoms and whether these effect can be maintained with a condensed course of a type of Cognitive Behavioral Therapy called Exposure and Response Prevention (EX/RP). You will be compensated for your time and travel. Participants must be between the ages of 18-55.

Obsessive-compulsive disorder (OCD) is a common psychiatric illness that affects up to 2-3% of the population. People with OCD experience anxiety-provoking, intrusive thoughts, known as obsessions, and feel compelled to perform repetitive behaviors, or compulsions. The only medications proven effective for OCD are serotonin reuptake inhibitors (SRIs), but even with SRI treatment, most patients continue to experience significant OCD symptoms, impaired functioning, and diminished quality of life. Recent evidence suggest that a different neurotransmitter, glutamate, may contribute to the symptoms in OCD. Medications that target glutamate hold promise for ameliorating symptoms for those patients continuing to suffer from OCD. In this study the investigators are recruiting patients to receive the drug ketamine, which is thought to modulate the neurotransmitter glutamate through the N-methyl-D-aspartate (NMDA), in a 2-week placebo controlled study.

Obsessive-Compulsive Disorder (OCD) is a chronic and disabling disorder that costs the economy over $2 billion annually and represents a significant public health problem. This study aims to build on our discovery that a potent NMDA receptor antagonist, ketamine, has rapid (in hours) and robust therapeutic effects in OCD. The proposed projects test the acute mechanism of action of ketamine at the level of molecules, circuits, and network synchrony to determine how NMDA receptor antagonism modifies the underlying pathology of OCD to relieve repetitive thoughts and behaviors.

Roughly one-third of patients with obsessive-compulsive disorder (OCD) do not experience significant clinical benefit from first-line interventions such as pharmacotherapy with selective serotonin reuptake inhibitors (SSRI) or cognitive behavioral therapy (CBT). Furthermore, OCD patients typically experience the full treatment benefits of first-line interventions only after a time-lag of two to three months. Inadequate symptom relief and delay of symptom relief from first-line treatments are sources of substantial morbidity and decreased quality of life in OCD patients. Converging lines of evidence from neuroimaging, genetic and pharmacological studies support the importance of glutamate abnormalities in the pathogenesis of OCD.

Rapid anti-OCD effects from a single intravenous dose of ketamine can persist for at least 1 week in some OCD patients with constant intrusive thoughts. This is the first randomized, controlled trial to demonstrate that a drug affecting glutamate neurotransmission can reduce OCD symptoms without the presence of an SRI and is consistent with a glutamatergic hypothesis of OCD.

This proposal will obtain preliminary data on the effect of a single sub-anesthetic dose of a sedative on cigarette craving and smoking behavior as well as measuring tolerability and acceptability.

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.

Alcohol use disorders remain a significant public health problem. The pharmacological facilitation of behavioral treatment represents a promising strategy for addressing disordered drinking. Alcohol use disorders are recognized to be associated with various vulnerabilities that complicate the course of treatment and that may be amenable to glutamate modulators. The purpose of this randomized, double-blind, controlled trial is to test various glutamate modulators in conjunction with motivational enhancement therapy (MET) for alcohol use disorders.

Cannabis use disorders remain a significant public health problem. The pharmacological facilitation of behavioral treatment represents a promising strategy for addressing disordered cannabis use. Cannabis use disorders are recognized to be associated with various vulnerabilities that complicate the course of treatment and that may be amenable to glutamate modulators. The purpose of this single blind open-label trial is to test the feasibility of administering glutamate modulators in conjunction with motivational enhancement therapy (MET) and mindfulness based relapse prevention (MBRP) for cannabis use disorders.

Pharmacotherapy and behavioral treatments for alcohol use disorder are limited in their effectiveness, and new treatments with innovative mechanisms would be valuable. In this study, a single ketamine infusion was found to improve measures of drinking in persons with alcohol dependence engaged in motivational enhancement therapy. These preliminary data suggest new directions in integrated pharmacotherapy-behavioral treatments for alcohol use disorder.

Maladaptive reward memories (MRMs) are involved in the development and maintenance of acquired overconsumption disorders, such as harmful alcohol and drug use. However, reliable means for pharmacologically weakening MRMs in humans remain elusive. This study demonstrates that ketamine is able to disrupt MRMs in hazardous drinkers when administered immediately after their retrieval.

This is an outpatient randomized within subject placebo-controlled human laboratory investigation of analgesia (as assessed with quantitative sensory testing; QST) from ketamine alone and in combination with hydromorphone in buprenorphine maintained participants. The goals of this project are to characterize the analgesic, subjective, and physiologic effects of ketamine combined with hydromorphone in patients on buprenorphine maintenance for opioid use disorder.

This study evaluates the feasibility of a treatment paradigm that involves naturalistic cocaine use opportunities in the context of psychotherapy aimed at utilizing these opportunities therapeutically.

Alcohol use disorders remain a significant public health problem. The pharmacological facilitation of behavioral treatment represents a promising strategy for addressing disordered drinking. Alcohol use disorders are recognized to be associated with various vulnerabilities that complicate the course of treatment and that may be amenable to glutamate modulators. The purpose of this randomized, double-blind, controlled trial is to test various glutamate modulators in conjunction with motivational enhancement therapy (MET) for alcohol use disorders.

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. The authors reviewed seven studies on the efficacy of ketamine in the treatment of SUDs. Both cocaine studies found improvements in craving, motivation, and decreased cocaine use rates. Studies of alcohol (2) and opioid use disorders (3) found improvement in abstinence rates in the ketamine group, with significant between-group effects noted for up to two years following a single infusion.

Opioid dependence is a substantial problem associated with significant morbidity and mortality. Extended-release naltrexone has been found effective at reducing opioid use and maintaining abstinence, but its use has been limited by the difficulties encountered with treatment initiation, which involves detoxification from opioids and oral naltrexone titration. Improving the likelihood of a successful transition to naltrexone is therefore an important public health goal. N-methyl-D-aspartate receptor (NMDA) antagonism has been found to alleviate the signs and symptoms of withdrawal from opioids, as well as to address adaptations associated with chronic opioid use, such as opioid-induced hyperalgesia (increased pain sensitivity). These benefits may persist for at least 72 hours after a single dose. NMDA antagonism may therefore facilitate a rapid transition to naltrexone by reducing discomfort, improving motivation, and ameliorating adaptations associated with drug dependence, such as craving and arousal. The purpose of this trial is to assess the feasibility of NMDA antagonist-assisted naltrexone initiation in opioid dependent individuals. After administration of extended-release naltrexone, participants will be followed for 4 weeks, and transitioned to appropriate care subsequently (oral naltrexone, extended-release naltrexone).

Cocaine dependence involves problematic neuroadaptations, such as heightened reactivity to cocaine cues, that may be responsive to pharmacological modulation of glutamatergic circuits. Despite promising preclinical findings with n-methyl-d-aspartate receptor (NMDAr) modulators, studies with human subjects have been unsuccessful to date. The purpose of this investigation is to examine the effects of the NMDAr antagonist ketamine, recently found to have potent therapeutic effects in humans, on cue-induced craving and impaired motivation for quitting cocaine in cocaine dependent participants, 24-hours post-infusion.

The primary objective of this study is to evaluate the abuse potential of intranasal esketamine (112 milligram and 84 mg) compared to racemic intravenous ketamine (0.5 mg/kg) in nondependent, recreational polydrug users of perception-altering drugs.

This study evaluates the feasibility of a treatment paradigm that involves naturalistic cocaine use opportunities in the context of psychotherapy aimed at utilizing these opportunities therapeutically.

The purpose of this study is to evaluate the efficacy of ketamine in reducing depressive symptoms in subjects with a comorbid major depressive episode and alcohol dependence. The investigators hypothesize the following for the present study: A single dose of ketamine will induce a rapid, robust and sustained reduction in depressive symptoms in subjects with a comorbid major depressive episode and alcohol dependence relative to placebo as defined by change in Hamilton Depression Rating Scale total scores at 72 hours post infusion. A single dose of ketamine can be delivered safely, with minimal adverse events or complications, in subjects with a comorbid major depressive episode and alcohol dependence.

Ketamine psychedelic therapy (KPT): a review of the results of ten years of research