The Pharmacological Management of Ketamine Use Disorder: A Systematic Review.
Emmert Roberts, Elizabeth Sanderson, Irene Guerrini
Journal of Addiction Medicine DOI: 10.1097/ADM.0000000000001340 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review Case report Peer reviewed |
|---|---|
| Sample size | 368 |
| Population | People with ketamine use disorder |
| Interventions | Benzodiazepine regimens haloperidol naltrexone lamotrigine paliperidone palmitate plus bupropion |
| Topics | Esketamine Ketamine |
| Keywords | Ketamine addiction Substance abuse treatment Psychopharmacology Addiction medicine Drug dependence |
| Citations | 14 |
| Key findings | Only very low-quality evidence from 12 studies (mostly case reports) supports any pharmacological intervention for ketamine use disorder, with benzodiazepine regimens showing the most potential for intoxication and withdrawal, and naltrexone, lamotrigine, or paliperidone palmitate plus bupropion for craving or relapse prevention. |
Abstract
There has been limited evidence synthesis examining treatment of ketamine use disorder. We aimed to conduct a systematic review to assess the efficacy and tolerability of pharmacological interventions in the management of ketamine use disorder. We searched MEDLINE, EMBASE, PsychINFO, and CENTRAL (Cochrane Central Register of Controlled Trials) from database inception to November 14, 2023, for studies of any design that reported on any pharmacological intervention in the management of ketamine use disorder. We extracted any reported measure of efficacy or tolerability and assessed outcome quality using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) framework. We planned to combine outcomes using random-effects meta-analysis, where this was not possible results were reported narratively. Twelve studies met the inclusion criteria reporting on 368 participants. These comprised 1 controlled trial, 2 retrospective case series, and 9 case reports. Two studies reported on ketamine intoxication, 6 on withdrawal, and 4 on craving/relapse prevention. All studies reported only descriptive outcomes, and all evidence was of very low quality. Benzodiazepine regimens and haloperidol were reported to have potential utility in intoxication and withdrawal, whereas naltrexone, lamotrigine, and a combination of paliperidone palmitate and bupropion were reported to have potential utility in craving/relapse prevention. There is a paucity of research into pharmacological management of ketamine use disorder. The limited very low-quality evidence suggests benzodiazepine regimens may be most salient for future exploration in management of ketamine intoxication and withdrawal, whereas case reports suggest naltrexone, lamotrigine, and paliperidone palmitate plus bupropion may potentially merit further investigation with regard to craving/relapse prevention.
Comparable studies
Other systematic reviews and meta-analyses on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| The effect of a single dose of intravenous ketamine on suicidal ideation: a systematic review and individual participant data meta-analysis Depressed patients with suicidal ideation at baseline | 2017 | Systematic review and individual participant data meta-analysis | n = 167 |
| Ketamine use: a review Ketamine users | 2011 | Systematic review | |
| Ketamine and Other NMDA Antagonists: Early Clinical Trials and Possible Mechanisms in Depression Participants with major depression in placebo-controlled, double-blind, randomized... | 2015 | Systematic review and meta-analysis | |
| Ketamine and postoperative pain – a quantitative systematic review of randomised trials Surgical patients from 25 countries | 2004 | Systematic review | n = 2,839 |
| Side-effects associated with ketamine use in depression: a systematic review. Patients with depression | 2018 | Systematic review |
Citations in the library
Cited by 11
- The landscape of ketamine use disorder: Patient experiences and perspectives on current treatment options. Addiction April 28, 2025
- Neurobiological Mechanisms of Ketamine Use, its Addiction, and Withdrawal: A Mini Review. Current reviews in clinical and experimental pharmacology March 3, 2025
- Grayken lessons: a multidisciplinary approach to care for a patient with severe ketamine use disorder. Addiction Science & Clinical Practice February 4, 2026
- Naltrexone in the Treatment of Ketamine Use Disorders: A Case Report and Literature Review. Journal of Addiction Medicine October 2, 2025
- Hype or hope? The developing evidence base for psychedelic treatment of addiction disorders. The British Journal of Psychiatry March 21, 2025
and 6 more in the library
Cites 7
- Ketamine use: a review Addiction July 21, 2011
- Real-world effectiveness of ketamine in treatment-resistant depression: A systematic review & meta-analysis. Journal of Psychiatric Research May 1, 2022
- Adjunctive Ketamine With Relapse Prevention–Based Psychological Therapy in the Treatment of Alcohol Use Disorder American Journal of Psychiatry January 11, 2022
- Harm related to recreational ketamine use and its relevance for the clinical use of ketamine. A systematic review and comparison study Expert Opinion on Drug Safety June 26, 2021
- Increasing Prevalence of Ketamine in Drivers in New York City Including the Identification of 2-Fluoro-Deschloroketamine. Journal of Analytical Toxicology September 17, 2021
and 2 more in the library