Ketamine an 'Intriguing New Therapy' for Alcoholism

Megan Brooks

January 25, 2022

Three weekly infusions of the dissociative anesthetic ketamine coupled with mindfulness-based relapse prevention therapy may help adults with alcohol use disorder (AUD) maintain abstinence, new research suggests.

Preliminary results from a phase 2, double-blind, placebo-controlled trial show ketamine was well tolerated and, compared with placebo, associated with more days of abstinence from alcohol at 6 months.

The results suggest ketamine plus psychological therapy may be a "new, relatively brief treatment, that has long lasting effects in AUD," Celia Morgan, PhD, professor of psychopharmacology, University of Exeter, Exeter, United Kingdom, told Medscape Medical News.

The study was published online January 11 in the American Journal of Psychiatry.

Target Depression

Depressive symptoms are common in patients under treatment for AUD and increase relapse risk.

"Ketamine may support alcohol abstinence by temporarily alleviating depressive symptoms during the high-risk relapse period in the weeks after detoxification," the investigators note.

Ketamine may also provide a "temporary boost to synaptogenesis and neurogenesis, which may allow psychological therapies and new strategies for managing addiction to embed more readily," they add.  

To test these theories, the researchers recruited 96 adults (mean age, 44 years, 35 women) with severe AUD to participate in the trial.

All participants had to abstain from alcohol for at least 24 hours before the trial started and have a reading of 0.0 on a breath alcohol test at the baseline visit.

Participants were randomly allocated to one of four groups:

  1. three weekly ketamine infusions of 0.8 mg/kg IV over 40 minutes plus psychological therapy

  2. three saline infusions plus psychological therapy

  3. three ketamine infusions plus alcohol education

  4. three saline infusions plus alcohol education

The primary outcome was self-reported percentage of days abstinent, as well as confirmed alcohol relapse at 6-month follow-up.

At 6-month follow-up, ketamine was associated with a significantly greater number of days abstinent from alcohol (mean difference, 10.1%; 95% CI, 1.1 - 19.0), "although confidence intervals were wide, consistent with a proof-of-concept study," the authors note.

The greatest reduction in total days off alcohol occurred in the ketamine plus relapse-prevention therapy group compared with the saline plus alcohol education group (mean difference, 15.9%; 95% CI, 3.8 - 28.1).

There was no significant difference in relapse rate between the ketamine and placebo groups. No serious adverse effects were reported in any participant.

Growing Evidence

These findings support some other studies that have also suggested a benefit of ketamine in AUD. 

As reported by Medscape Medical News, one recent study found a single infusion of ketamine combined with counseling may help alcohol-dependent patients curb their drinking.

A separate study showed that a single dose of ketamine plus therapy that focused on reactivating drinking-related "maladaptive reward memories" reduced drinking urges and alcohol intake more than just ketamine or a placebo infusion alone. 

"That ketamine can reduce both alcohol use and depression in AUD is encouraging therapeutically," the researchers write.

"While a clear link between depression and AUD is acknowledged, alcohol and mental health services still struggle to meet the needs of dual-diagnosis patients, so ketamine may represent a solution to this long-standing comorbidity," they add.

Morgan told Medscape Medical News that adjunctive ketamine with relapse-prevention therapy is "currently being delivered in Awakn Clinics in the UK and Norway, but we need to conduct the phase 3 trial in order to make the treatment more widely accessible."

An "Intriguing New Therapy"

Reached for comment, Timothy Brennan, MD, MPH, chief of clinical services, Addiction Institute of Mount Sinai in New York City, said ketamine "continues to be an intriguing new therapy for a variety of mental health conditions."

"Unfortunately, the study did not show any difference in rates of relapse to alcohol, though an improvement in days of abstinence is certainly noteworthy," Brennan told Medscape Medical News.

"Because this was just a proof-of-concept study and did not compare ketamine to any FDA-approved pharmacotherapy for alcohol, it remains too early to recommend ketamine infusions to those suffering from alcohol use disorder," he cautioned.

The study was supported by the Medical Research Council. Morgan has received royalties for KARE (Ketamine for Reduction of Alcoholic Relapse) therapy license distribution. KARE therapy is licensed from University of Exeter to Awakn Life Sciences. Morgan has received research funding from Awakn Life Sciences and has served as a consultant for Janssen Pharmaceuticals. Other co-authors have disclosed relationships with industry; the full list can be found with the original article. Brennan has disclosed no relevant financial relationships.

Am J Psychiatry. Published online January 11, 2022. Full text

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