Key considerations for the use of ketamine and esketamine for the treatment of depression: focusing on administration, safety, and tolerability
M. Kritzer, C. Pae, P. Masand
Expert Opinion on Drug Safety April 27, 2022 DOI: 10.1080/14740338.2022.2069749 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Narrative review Randomized Placebo-controlled Double-blind Peer reviewed |
|---|---|
| Interventions | Ketamine Esketamine R-ketamine |
| Topics | Depression Esketamine Ketamine |
| Key findings | The authors conclude that intravenous ketamine and intranasal esketamine are validated rapid-acting treatments for depression and suicidal ideation, but that repeated dosing generally provides only about two to three weeks of relief. They recommend further investigation into optimal dosing and frequency, strategies to prolong therapeutic effects, co-administration with somatic and neuromodulation treatments, R-ketamine as a possible future antidepressant, and long-term monitoring for adverse effects. |
Abstract
ABSTRACT Introduction Racemic ketamine, a derivative of phencyclidine, has been used as a dissociative anesthetic since 1970. In 2000, the first randomized controlled trial showed a rapid relief of depressive symptoms. Since then, intravenous ketamine and intranasal S-ketamine have been validated for the treatment of depression and suicidal ideation following dose-response and double-blind placebo-controlled clinical trials. In clinical practice, after dose titration and with repeated treatments, patients may experience approximately 2–3 weeks of symptomatic relief from depression. Areas covered Areas covered in this narrative review include mechanism of action, dosing, safety, and tolerability. Some attention is paid to the possibility of R-ketamine as a future antidepressant. Expert opinion We recommend further investigation into treatment dosing and frequency strategies as well as approaches that prolong the therapeutic effects. The current fixed dosing of esketamine for obese individuals may be insufficient. Additional investigation into co-administration with somatic and neuromodulation treatments needs investigation. Finally, continuing to monitor research subjects and patients long-term for the emergence of adverse effects on cognition or other organ systems is critical.
Comparable studies
Other narrative reviews on esketamine 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 | |
| Long-term safety of ketamine and esketamine in treatment of depression | 2022 | Review | |
| Ketamine, Esketamine, and Arketamine: Their Mechanisms of Action and Applications in the Treatment of Depression and Alleviation of Depressive Symptoms. | 2024 | Review | |
| Variations in BDNF and Their Role in the Neurotrophic Antidepressant Mechanisms of Ketamine and Esketamine: A Review. Patients with depression | 2024 | Narrative review | |
| The Possible Application of Ketamine in the Treatment of Depression in Alzheimer’s Disease | 2022 | Review |
Citations in the library
Cited by 6
- Safety and tolerability of NN-dimethyltryptamine (DMT) in healthy volunteers and Major Depressive Disorder (MDD) patients: A systematic review of early-phase clinical trials. Progress in Neuro-Psychopharmacology and Biological Psychiatry June 7, 2025
- TOLERANCE AND ACCEPTABILITY OF INTRAVENOUS KETAMINE THERAPY FOR TREATMENT RESISTANT DEPRESSION: A MIXED METHODS ASSESSMENT Journal of Pakistan Psychiatric Society March 3, 2023
- Ketamine for Depression in Serious Illness: Evidence, Safety, and Practical Approaches. Journal of Pain and Symptom Management August 1, 2026
- Continuous ketamine infusion for surgical patients in the intensive care unit: a systematic review and meta-analysis of randomized controlled trials with GRADE assessment. Critical Care January 23, 2026
- Pharmacokinetics, Safety, and Tolerability of (R)-Ketamine Hydrochloride Injection, a Novel Rapid-Acting Antidepressant, in Healthy Chinese Subjects. Pharmaceuticals July 21, 2025
and 1 more in the library
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- Quality of Acute Psychedelic Experience Predicts Therapeutic Efficacy of Psilocybin for Treatment-Resistant Depression Frontiers in Pharmacology January 17, 2018
- Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation American Journal of Psychiatry March 17, 2021
- Efficacy and Safety of Intranasal Esketamine for the Rapid Reduction of Symptoms of Depression and Suicidality in Patients at Imminent Risk for Suicide: Results of a Double-Blind, Randomized, Placebo-Controlled Study American Journal of Psychiatry April 16, 2018
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