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.
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.
Safety and efficacy of maintenance ketamine treatment in patients with treatment-refractory generalised anxiety and social anxiety disorders
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.
Ketamine as a novel treatment for major depressive disorder and bipolar depression: a systematic review and quantitative meta-analysis.
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.
Antidepressant efficacy of ketamine in treatment-resistant major depression: a two-site randomized controlled trial
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.
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.
Rapid antidepressant effects of repeated doses of ketamine compared with electroconvulsive therapy in hospitalized patients with major depressive disorder.
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.
Antidepressant, mood stabilizing and procognitive effects of very low dose sublingual ketamine in refractory unipolar and bipolar 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.
Double-blind, placebo-controlled, dose-ranging trial of intravenous ketamine as adjunctive therapy in treatment-resistant depression (TRD)
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.
A Double-Blind, Randomized, Placebo-Controlled, Dose-Frequency Study of Intravenous Ketamine 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. 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.
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.
Randomized Controlled Crossover Trial of Ketamine in Obsessive-Compulsive Disorder: Proof-of-Concept
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.
Substance 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.
A Single Ketamine Infusion Combined With Motivational Enhancement Therapy for Alcohol Use Disorder: A Randomized Midazolam-Controlled Pilot Trial
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.
Ketamine psychedelic therapy (KPT): a review of the results of ten years of research
The Effect of a Single Dose of Intravenous Ketamine on Suicidal Ideation: A Systematic Review and Individual Participant Data Meta-Analysis
Suicide is a public health crisis with limited treatment options. The authors conducted a systematic review and individual participant data meta-analysis examining the effects of a single dose of ketamine on suicidal ideation and concluded that ketamine rapidly reduced suicidal thoughts, within 1 day and for up to 1 week in depressed patients with suicidal ideation.