Ketamine and Electroconvulsive Therapy for Depression.
Journal of neurosurgical anesthesiology October 1, 2018 DOI: 10.1097/ana.0000000000000524 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Interventions | Ketamine Esketamine |
| Dose | 0.5 mg/kg over 40 minutes; lower doses 0.2 to 0.5 mg/kg; higher doses up to 0.8 mg/kg |
| Duration | Benefits last about 7 to 12 days; repeated sessions twice to 3 times a week for up to 2 weeks or longer |
| Topics | Depression Esketamine Ketamine |
| Key findings | Ketamine given intravenously at 0.5 mg/kg over 40 minutes markedly reduces depression severity within 1 hour to 1 day, with about a third of patients remitting and over half showing at least 50% reduction in depression ratings. Benefits last only about 7 to 12 days, with earlier relapse in bipolar than unipolar depression. The authors state that ketamine's antidepressant mechanism remains unresolved. |
Abstract
K anesthesia was introduced about half a century ago. In recent decades, this drug, in subanesthetic doses, has also demonstrated efficacy for off-label indications including treating acute and chronic pain, treating agitation, treating depression, and inducing sedation. Thus, there are studies of subanesthetic dosing with ketamine for treating pain in emergency medicine settings, treating postsurgical pain, treating medication-refractory headache, reducing agitation and violence in prehospital and emergency settings, and sedating children in dental and radiological settings.1 The last decade has also seen a spurt of research on subanesthetic dosing with ketamine in patients with depression.1 Before the advent of ketamine, the treatment of depression was based on variations on a theme of neuromodulation of serotonin, norepinephrine, and dopamine using drugs that had a wide range of actions on these neurotransmitter systems. Ketamine does not increase or decrease the reuptake of these neurotransmitters, does not affect their synthesis or metabolism, and does not act on the receptors on which they act. Although the antidepressant mechanism of ketamine remains unresolved, it appears that ketamine is not the only drug with psychotomimetic properties that has efficacy against depression and other psychiatric disorders; psilocybin, ayahuasca, methylenedioxymethamphetamine, and lysergic acid diethylamide also benefit patients, including those with difficult-to-treat and medication-refractory disorders.2–4 With regard to ketamine and depression, here is a summary of the field as it currently stands. Ketamine, most commonly administered intravenously in a dose of 0.5 mg/kg over 40 minutes, markedly attenuates the severity of depression within 1 hour to 1 day of administration in patients with major depression. Most of the evidence comes from studies on patients with severe, chronic, medication-refractory major depressive disorder. Astonishingly, as many as a third of patients experience remission of illness within a day of ketamine treatment, while over half show at least 50% attenuation of depression ratings.1 However, the benefits last for only about 7 to 12 days, with depression relapsing earlier in patients with bipolar relative to those with unipolar depression. Lower doses of ketamine (0.2 to 0.5 mg/kg) may also be effective, but probably less so, and higher doses (up to 0.8 mg/kg) may benefit patients who do not respond to standard doses. Repeated ketamine sessions, twice to 3 times a week, for up to 2 weeks or longer, can extend treatment gains. Ketamine can be administered intravenously, intramuscularly, subcutaneously, orally, intranasally, and in other ways, but dosing must be adjusted to compensate for variable rate and quantum of absorption.5 It is suggested, but not confirmed, that the S-enantiomer of the drug, esketamine, is as effective as, and better tolerated than, racemic ketamine.6 Industry-driven research is currently examining possibilities for acute and continuation treatment of depression with intranasal esketamine.7 Although ketamine has also been studied for refractory anxiety disorders, its principal (off-label) indication in psychiatry appears to be the treatment of major
Comparable studies
Other narrative reviews on ketamine for depression, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation Adults with treatment-resistant depression | 2021 | Review | |
| Ketamine: a paradigm shift for depression research and treatment | 2019 | Review | |
| Rapid‐acting antidepressant ketamine, its metabolites and other candidates: A historical overview and future perspective | 2019 | Review | |
| Ketamine: A tale of two enantiomers | 2020 | Review | |
| Molecular mechanisms underlying the antidepressant actions of arketamine: beyond the NMDA receptor | 2021 | Review |
Citations in the library
Cites 9
- Psilocybin with psychological support for treatment-resistant depression: six-month follow-up. Psychopharmacology November 8, 2017
- Efficacy and Safety of Intranasal Esketamine Adjunctive to Oral Antidepressant Therapy in Treatment-Resistant Depression JAMA Psychiatry December 27, 2017
- 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for post-traumatic stress disorder in military veterans, firefighters, and police officers: a randomised, double-blind, dose-response, phase 2 clinical trial. The Lancet Psychiatry May 1, 2018
- Antidepressive, anxiolytic, and antiaddictive effects of ayahuasca, psilocybin and lysergic acid diethylamide (LSD): a systematic review of clinical trials published in the last 25 years Therapeutic Advances in Psychopharmacology March 18, 2016
- Ketamine for Depression, 4: In What Dose, at What Rate, by What Route, for How Long, and at What Frequency? The Journal of Clinical Psychiatry July 20, 2017
and 4 more in the library