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Adjunctive Ketamine With Relapse Prevention–Based Psychological Therapy in the Treatment of Alcohol Use Disorder

Meryem Grabski, Amy Mcandrew, Will Lawn, Beth Marsh, Laura Raymen, Tobias Stevens, Lorna Hardy, Fiona C Warren, Michael Bloomfield, Anna Borissova, Emily L. Maschauer, Rupert Broomby, Robert L. Price, Rachel Coathup, David Gilhooly, Edward Palmer, Richard Gordon-Williams, Robert D. Hill, J. A. Harris, Özden Merve Mollaahmetoğlu, Helen Valerie Curran, Brigitta Brandner, Anne Lingford‐hughes, Celia J. A. Morgan

American Journal of Psychiatry January 11, 2022 DOI: 10.1176/appi.ajp.2021.21030277 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Randomized controlled trial Placebo-controlled Double-blind Peer reviewed
Sample size 96
Population Patients with severe alcohol use disorder
Interventions Ketamine infusion Saline infusion Mindfulness-based relapse prevention therapy Alcohol education
Dose 0.8 mg/kg i.v. over 40 minutes
Duration Three weekly infusions, 6-month follow-up
Topics Addiction Ketamine Esketamine
Keywords Placebo Relapse prevention Abstinence Adverse effect Alcohol dependence Anesthesia Randomized controlled trial
Citations 169
Key findings Ketamine infusions led to significantly more days abstinent from alcohol at six months compared with placebo, though relapse rates did not differ significantly.

Abstract

Objective: Early evidence suggests that ketamine may be an effective treatment to sustain abstinence from alcohol. The authors investigated the safety and efficacy of ketamine compared with placebo in increasing abstinence in patients with alcohol use disorder. An additional aim was to pilot ketamine combined with mindfulness-based relapse prevention therapy compared with ketamine and alcohol education as a therapy control.

Methods: In a double-blind placebo-controlled phase 2 clinical trial, 96 patients with severe alcohol use disorder were randomly assigned to one of four conditions: 1) three weekly ketamine infusions (0.8 mg/kg i.v. over 40 minutes) plus psychological therapy, 2) three saline infusions plus psychological therapy, 3) three ketamine infusions plus alcohol education, or 4) three saline infusions plus alcohol education. The primary outcomes were self-reported percentage of days abstinent and confirmed alcohol relapse at 6-month follow-up.

Results: Ninety-six participants (35 women; mean age, 44.07 years [SD=10.59]) were included in the intention-to-treat analysis. The treatment was well tolerated, and no serious adverse events were associated with the study drug. Although confidence intervals were wide, consistent with a proof-of-concept study, there were a significantly greater number of days abstinent from alcohol in the ketamine group compared with the placebo group at 6-month follow-up (mean difference=10.1%, 95% CI=1.1, 19.0), with the greatest reduction in the ketamine plus therapy group compared with the saline plus education group (15.9%, 95% CI=3.8, 28.1). There was no significant difference in relapse rate between the ketamine and placebo groups.

Conclusions: This study demonstrated that treatment with three infusions of ketamine was well tolerated in patients with alcohol use disorder and was associated with more days of abstinence from alcohol at 6-month follow-up. The findings suggest a possible beneficial effect of adding psychological therapy alongside ketamine treatment.

In the evidence

This study is part of the evidence base for a synthesis in the library. Here is how each one recorded it.

  • Ketamine infusions led to significantly more days abstinent at six months compared with placebo, but relapse rates did not differ significantly between groups.

    Synthesized

Comparable studies

Other randomized controlled trials on ketamine for addiction, most cited first.

Study Year Design Participants
Ketamine psychotherapy for heroin addiction: immediate effects and two-year follow-up. Detoxified heroin-addicted patients 2002 Randomized controlled trial n = 70
A Single Ketamine Infusion Combined With Motivational Enhancement Therapy for Alcohol Use Disorder: A Randomized Midazolam-Controlled Pilot Trial. Adults with alcohol dependence engaged in motivational enhancement therapy 2019 Randomized controlled trial n = 40
A Single Ketamine Infusion Combined With Mindfulness-Based Behavioral Modification to Treat Cocaine Dependence: A Randomized Clinical Trial. Cocaine-dependent adults 2019 Randomized controlled trial n = 55
Single Versus Repeated Sessions of Ketamine-Assisted Psychotherapy for People with Heroin Dependence Detoxified inpatients with heroin dependence 2007 Randomized controlled trial n = 59
Association of Combined Naltrexone and Ketamine With Depressive Symptoms in a Case series of Patients With Depression and Alcohol Use Disorder 2019 Randomized controlled trial

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