Ketamine for Adults With Substance Use Disorders

Key Messages

What Is the Issue

• Accumulating research has demonstrated that subanesthetic doses of ketamine have rapid and sustained antidepressant effects. In 2019, the US FDA approved the S-enantiomer of ketamine (esketamine) for the treatment of patients with treatment-resistant depression.
• Since then, there has been interest in the development of ketamine for the treatment of a broad range of mental health conditions beyond depression, including substance use disorders (SUDs).
• Decision-makers want to know if there is any evidence to support the use of ketamine for treating SUDs in adults.

What Did We Do?

• To inform decisions about using ketamine for treating SUDs, we sought to identify and summarize the literature comparing the clinical and cost-effectiveness of ketamine with placebo or no treatment, with alternative interventions, or among ketamine administered via different routes for SUDs. We also searched for evidence-based recommendations for the use of ketamine for SUDs.
• A research information specialist conducted a literature search of peer-reviewed and grey literature sources published between January 1, 2018, and November 28, 2023. One reviewer screened citations for inclusion based on predefined criteria, critically appraised the included studies, and narratively summarized the findings.

What Did We Find?

• We found 2 systematic reviews (SRs) and 1 randomized controlled trial (RCT) on the use of ketamine for the treatment of patients with alcohol use disorder (AUD), cocaine use disorder (CUD), and opioid use disorder (OUD).
• Evidence from 2 SR suggests that a combination of ketamine infusion and psychotherapy treatment may be effective in promoting abstinence and reduced consumption of alcohol and cocaine use. There were mixed results regarding the effect of ketamine on withdrawal and craving.
• The effects of ketamine on OUD were inconclusive as the results were derived from a single study with a small sample size. Similarly, the effects of ketamine on health care utilization (e.g., hospital readmission, emergency department visit) in patients with severe AUD reported in a RCT were also inconclusive due to the small sample size.
• Adverse events associated with ketamine treatment included the dissociative and psychotomimetic effects and nondissociative effects. The authors of the included SR reported that these events were mild and transient.
• We did not find any studies on the cost-effectiveness or evidence-based guidelines of ketamine for treating SUDs that met our criteria for this review.

What Does It Mean?

• The conclusions on the positive effects of ketamine for AUD and CUD should be interpreted with caution due to the high risk of bias of the studies included in the SRs.
• There is a need for more robust clinical trials with larger sample sizes, blinding, and low risk of bias to provide more accurate findings on clinical efficacy, dosing strategies, and safety profile of ketamine for the treatment of AUD, CUD, and OUD.
• Additional studies on other substances of abuse (e.g., nicotine, amphetamines, and cannabis) may provide important insights into the overall efficacy of ketamine in the treatment of SUDs.