Therapeutic Potentials of Ketamine and Esketamine in Obsessive–Compulsive Disorder (OCD), Substance Use Disorders (SUD) and Eating Disorders (ED): A Review of the Current Literature
Giovanni Martinotti, Stefania Chiappini, Mauro Pettorruso, Alessio Mosca, Andrea Miuli, Francesco di Carlo, Giacomo D’andrea, Roberta Collevecchio, Ilenia di Muzio, Stefano L. Sensi, Massimo Di Giannantonio
Brain Sciences June 27, 2021 DOI: 10.3390/brainsci11070856 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review Peer reviewed |
|---|---|
| Interventions | Ketamine Esketamine |
| Topics | Ketamine Addiction Esketamine |
| Keywords | Eating disorders Obsessive compulsive Substance use Clinical psychology Psychotherapist |
| Citations | 114 |
| Key findings | Ketamine and esketamine show promise for treating OCD, eating disorders, and substance use disorders, but solid evidence for benefits in the OCD spectrum and addiction is still lacking. |
Abstract
The obsessive-compulsive spectrum refers to disorders drawn from several diagnostic categories that share core features related to obsessive-compulsive disorder (OCD), such as obsessive thoughts, compulsive behaviors and anxiety. Disorders that include these features can be grouped according to the focus of the symptoms, e.g., bodily preoccupation (i.e., eating disorders, ED) or impulse control (i.e., substance use disorders, SUD), and they exhibit intriguing similarities in phenomenology, etiology, pathophysiology, patient characteristics and clinical outcomes. The non-competitive N-methyl-D-aspartate receptor (NMDAr) antagonist ketamine has been indicated to produce remarkable results in patients with treatment-resistant depression, post-traumatic stress disorder and OCD in dozens of small studies accrued over the past decade, and it appears to be promising in the treatment of SUD and ED. However, despite many small studies, solid evidence for the benefits of its use in the treatment of OCD spectrum and addiction is still lacking. Thus, the aim of this perspective article is to examine the potential for ketamine and esketamine in treating OCD, ED and SUD, which all involve recurring and intrusive thoughts and generate associated compulsive behavior. A comprehensive and updated overview of the literature regarding the pharmacological mechanisms of action of both ketamine and esketamine, as well as their therapeutic advantages over current treatments, are provided in this paper. An electronic search was performed, including all papers published up to April 2021, using the following keywords ("ketamine" or "esketamine") AND ("obsessive" OR "compulsive" OR "OCD" OR "SUD" OR "substance use disorder" OR "addiction" OR "craving" OR "eating" OR "anorexia") NOT review NOT animal NOT "in vitro", on the PubMed, Cochrane Library and Web of Science online databases. The review was conducted in accordance with preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. The use and efficacy of ketamine in SUD, ED and OCD is supported by glutamatergic neurotransmission dysregulation, which plays an important role in these conditions. Ketamine's use is increasing, and preliminary data are optimistic. Further studies are needed in order to better clarify the many unknowns related to the use of both ketamine and esketamine in SUD, ED and OCD, and to understand their long-term effectiveness.
In the evidence
This study is part of the evidence base for a synthesis in the library. Here is how each one recorded it.
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Ketamine and esketamine appear promising for substance use disorders, but solid evidence for benefit in addiction is still lacking.
Synthesized
Comparable studies
Other systematic reviews and meta-analyses on ketamine for addiction, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Ketamine use: a review Ketamine users | 2011 | Systematic review | |
| Ketamine for the treatment of mental health and substance use disorders: comprehensive systematic review | 2021 | Systematic review | |
| Efficacy of ketamine intervention to decrease alcohol use, cravings, and withdrawal symptoms in adults with problematic alcohol use or alcohol use disorder: A systematic review and comprehensive analysis of mechanism of actions. People with harmful alcohol use, alcohol craving, or alcohol withdrawal states,... | 2022 | Systematic review | n = 634 |
| Ketamine Treatment for Alcohol Use Disorder: A Systematic Review. Adult patients with alcohol use disorder, heavy drinkers, or those undergoing alcohol... | 2023 | Systematic review | n = 854 |
| Is there a risk of addiction to ketamine during the treatment of depression? A systematic review of available literature. Adult patients with depression | 2025 | Systematic review | n = 2,174 |
Citations in the library
Cited by 49
- "This Is Something That Changed My Life": A Qualitative Study of Patients' Experiences in a Clinical Trial of Ketamine Treatment for Alcohol Use Disorders. Frontiers in Psychiatry 2021
- Classic and non‐classic psychedelics for substance use disorder: A review of their historic, past and current research Addiction Neuroscience June 22, 2022
- Ketamine as a Treatment for Anorexia Nervosa: A Narrative Review Nutrients November 20, 2021
- Redefining Ketamine Pharmacology for Antidepressant Action: Synergistic NMDA and Opioid Receptor Interactions? American Journal of Psychiatry March 1, 2025
- Esketamine in treatment-resistant depression patients comorbid with substance-use disorder: A viewpoint on its safety and effectiveness in a subsample of patients from the REAL-ESK study European Neuropsychopharmacology May 4, 2023
and 44 more in the library
Cites 30
- Mechanisms of Ketamine Action as an Antidepressant Molecular Psychiatry March 13, 2018
- The effect of a single dose of intravenous ketamine on suicidal ideation: a systematic review and individual participant data meta-analysis American Journal of Psychiatry October 3, 2017
- Ketamine – More mechanisms of action than just NMDA blockade Trends in Anaesthesia and Critical Care March 22, 2014
- Ketamine Psychedelic Therapy (KPT): A Review of the Results of Ten Years of Research Journal of Psychoactive Drugs June 1, 1997
- Ketamine psychotherapy for heroin addiction: immediate effects and two-year follow-up. Journal of Substance Abuse Treatment December 1, 2002
and 25 more in the library