Adjunctive Ketamine With Relapse Prevention-Based Psychological Therapy in the Treatment of Alcohol Use Disorder
This double-blind placebo-controlled trial (n=96) assessed the effectiveness of 1) three weekly ketamine infusions (56mg/70kg 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, in people with alcohol use disorder (AUD). Participants in the ketamine groups abstained from alcohol for a significantly longer number of days at 6-month follow-up, while the greatest abstinence was in the ketamine plus therapy group. Relapse times did not differ across the four groups.
Authors
- Valerie Curran
- Celia Morgan
- Will Lawn
Published
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.
Research Summary of 'Adjunctive Ketamine With Relapse Prevention-Based Psychological Therapy in the Treatment of Alcohol Use Disorder'
Introduction
Harmful alcohol use accounts for a substantial global disease burden, and a large proportion of people with alcohol use disorder (AUD) relapse despite existing pharmacological and behavioural treatments. Ketamine, an N-methyl-D-aspartate receptor antagonist, is of interest for AUD for several reasons: subanesthetic ketamine has established antidepressant effects (potentially relevant because depressive symptoms increase relapse risk), preclinical data indicate ketamine can promote synaptogenesis and neurogenesis (potentially enhancing responsiveness to psychological therapies), and a small number of clinical studies have reported reduced alcohol use when ketamine is given alongside psychotherapeutic interventions or other behavioural manipulations. The subjective, dissociative experiences produced by ketamine may also facilitate engagement with therapies such as mindfulness-based approaches. Bloomfield and colleagues designed a proof-of-concept Phase II trial to test whether three weekly subanesthetic intravenous ketamine infusions, given after initial abstinence, would increase abstinence compared with saline, and to pilot whether combining ketamine with manualised mindfulness-based relapse prevention (therapy) would enhance outcomes compared with ketamine plus an alcohol-education control. The trial therefore compared four arms (ketamine+therapy, ketamine+education, saline+therapy, saline+education) with the co-primary outcomes of percentage days abstinent and confirmed alcohol relapse at 6 months. The authors hypothesised ketamine+therapy would be most effective and saline+education least effective in sustaining abstinence.
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Study Details
- Study Typeindividual
- Journal
- Compound
- Topics
- Authors
- APA Citation
Grabski, M., McAndrew, A., Lawn, W., Marsh, B., Raymen, L., Stevens, T., Hardy, L., Warren, F., Bloomfield, M., Borissova, A., Maschauer, E., Broomby, R., Price, R., Coathup, R., Gilhooly, D., Palmer, E., Gordon-Williams, R., Hill, R., Harris, J., . . . Morgan, C. J. (2022). Adjunctive Ketamine With Relapse Prevention-Based Psychological Therapy in the Treatment of Alcohol Use Disorder. American Journal of Psychiatry, 179(2), 152-162. https://doi.org/10.1176/appi.ajp.2021.21030277
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Papers cited by this study that are also in Blossom
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Wilkinson, S. T., Taeho, G., Rhee et al. · Psychotherapy and Psychosomatics (2021)
Dakwar, E., Levin, F. R., Hart, C. L. et al. · American Journal of Psychiatry (2020)
Krupitsky, E. M., Grinenko, A. Y. · Journal of Psychoactive Drugs (1997)
Dakwar, E., Nunes, E. V., Hart, C. L. et al. · American Journal of Psychiatry (2019)
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Marsden, J., Kelleher, M., Dunbar, F. et al. · Addiction (2025)
Thurgur, H., Sessa, B., Higbed, L. et al. · Alcohol and Alcoholism (2025)
Aepfelbacher, J., Panny, B., Price, R. · Biological Psychiatry (2024)
Gent, E. M., Bryan, J. W., Cleary, M. A. et al. · Journal of Psychopharmacology (2024)
Heinzerling, K. G., Sergi, K., Linton, M. et al. · Frontiers in Psychiatry (2023)
Zafar, R., Siegel, M., Harding, R. et al. · Frontiers in Psychiatry (2023)
Jones, J. L. · Frontiers in Psychiatry (2023)
van der Meer, P. B., Fuentes, J. J., Kaptein, A. A. et al. · Frontiers in Psychiatry (2023)
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