Can mind-altering prescription medicines be safe? Lessons from ketamine and esketamine.
Clinical Toxicology August 1, 2024 DOI: 10.1080/15563650.2024.2380773 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Esketamine Ketamine |
| Keywords | Opioids Post-marketing surveillance Real world data Psychedelics hallucinogens Entheogens Psychoactive drugs Drug safety pharmacovigilance Drug monitoring Controlled substances Drug control |
| Citations | 9 |
| Key findings | Ketamine misuse is increasing, while esketamine misuse is not, suggesting that regulatory restrictions rather than pharmacological differences limit misuse. |
Abstract
Recent decades have witnessed an extraordinary global crisis of drug misuse. Although opioid analgesics receive the most attention, numerous other drugs have increased rates of misuse. Ketamine and esketamine offer a unique natural experiment to explore two medications that are similar pharmacologically but differ in their availability to users and in their regulation by government agencies. Multisystem "mosaic" surveillance of many drugs using real-world data has emerged in recent years. Ketamine and esketamine have been monitored concurrently. Ketamine is much more widely available than esketamine and shows clear signs of increasing misuse and abuse. In contrast, esketamine is difficult to detect in postmarket surveillance even though availability is increasing. Ketamine and esketamine offer insights regarding the safety of prescription medications with the potential for misuse. Since the pharmacology of ketamine and esketamine are similar, the regulatory apparatus may be the primary difference that limits misuse. Ketamine has few restrictions and can be prescribed or administered by many healthcare providers, and is available as an illicit drug. In contrast, the product labeling for esketamine has rigorous restrictions on its use. Many important issues remain to be addressed. We need a more rigorous evaluation of the natural experiment of ketamine and esketamine. How does this experience relate to the introduction of new psychedelics? Ketamine misuse use and misuse are increasing while esketamine use in increasing, but misuse is not increasing. It is reasonable to reevaluate the regulatory controls on ketamine to reduce its misuse and abuse.
Comparable studies
Other narrative reviews on esketamine, 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 | |
| The potential of ketamine for posttraumatic stress disorder: a review of clinical evidence. | 2023 | Review | |
| Variations in BDNF and Their Role in the Neurotrophic Antidepressant Mechanisms of Ketamine and Esketamine: A Review. Patients with depression | 2024 | Narrative review |
Citations in the library
Cited by 7
- Safety and efficacy with esketamine in treatment-resistant depression: long-term extension study. The International Journal of Neuropsychopharmacology June 6, 2025
- Lessons learned from the regulatory alignment in ketamine, esketamine and arketamine clinical trials: A cross-sectional analysis of protocols from ClinicalTrials.gov. Psychiatry Research August 1, 2025
- Increased recreational ketamine use and subsequent outbreak of urological complications in The Netherlands. Clinical Toxicology June 17, 2025
- A cross-national comparison of nonmedical and medical use of psychedelic drugs in the international cannabis policy study. International Journal of Drug Policy August 1, 2026
- Evaluating the abuse liability of ketamine in the treatment of mood disorders: A systematic review. Journal of Psychopharmacology June 24, 2026
and 2 more in the library
Cites 5
- R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Translational Psychiatry September 1, 2015
- Ketamine treatment for depression: opportunities for clinical innovation and ethical foresight. The Lancet Psychiatry April 5, 2017
- Ketamine and the neurobiology of depression: Toward next-generation rapid-acting antidepressant treatments Proceedings of the National Academy of Sciences November 27, 2023
- Characteristics of poisonings involving ketamine in the United States, 2019-2021. Journal of Psychopharmacology August 2023
- A survey of the clinical, off-label use of ketamine as a treatment for psychiatric disorders American Journal of Psychiatry July 1, 2017