The Pharmacological Management of Ketamine Use Disorder: A Systematic Review

Background: Over the past decade there has been a substantial expansion in research investigating the therapeutic use of ketamine for psychiatric disorders. However, comparatively less focus has been placed on treatments for 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.   

Methods: We searched Medline, Embase, PsychINFO and CENTRAL from database inception to 14th November 2023 for studies of any design that reported use of any pharmacological intervention in the management of ketamine use disorder. We extracted any reported measure of efficacy or tolerability and planned to assess outcome quality using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. We planned to combine outcomes using a random-effects meta-analysis and where this was not possible results were reported narratively. 

Results: Twelve studies met the inclusion criteria reporting on 368 participants. These comprised one controlled trial, two retrospective case series and nine case reports. Two studies reported on pharmacological treatments for ketamine intoxication, six for withdrawal and four for craving or relapse prevention with all studies reporting only descriptive outcomes. Both benzodiazepine regimens and haloperidol were reported to have utility in the management of intoxication and withdrawal. Whereas naltrexone, lamotrigine and a combination of paliperidone palmitate and bupropion were reported to have utility in the management of craving or relapse prevention. All available evidence was of very low quality.  

Conclusions: There is a paucity of research into the pharmacological management of ketamine use disorder. The limited very low quality evidence suggests benzodiazepine regimens appear to be the most salient treatment option for exploration in management of ketamine intoxication and withdrawal, whilst naltrexone, lamotrigine and paliperidone palmitate plus bupropion appear to merit further investigation with regards craving and relapse prevention.