Ketamine, an “intriguing new therapy” for alcoholism

Three weekly dissociative infusions anesthetic ketamine combined with mindfulness-based relapse prevention therapy can help adults with alcohol consumption (AUD) maintain abstinence, according to new research.

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

The results suggest that ketamine combined with psychological therapy could be a “relatively brief new treatment, which has long-lasting effects on AUD”, said Celia Morgan, PhD, professor of psychopharmacology at the University of Exeter, Exeter , UK. Medscape Medical News.

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

Target depression

Depressive symptoms are common in patients undergoing treatment for AUD and increase the risk of relapse.

“Ketamine may promote abstinence from alcohol by temporarily alleviating depressive symptoms during the high-risk relapse period in the weeks following detox,” note the investigators.

Ketamine may also provide “a temporary boost to synaptogenesis and neurogenesis, which may allow psychological therapies and novel addiction management strategies to integrate more easily,” they add.

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

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

Participants were randomly assigned to one of four groups:

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

  2. three saline infusions plus psychological therapy

  3. three infusions of ketamine plus alcohol education

  4. three saline infusions plus alcohol education

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

At 6-month follow-up, ketamine was associated with significantly more days abstinence from alcohol (mean difference, 10.1%; 95% CI, 1.1-19.0),” although the confidence intervals are wide, which is consistent with a proof-of-concept study,” the authors note.

The greatest reduction in total alcohol-free days occurred in the ketamine therapy plus relapse prevention group compared to the saline education plus alcohol group (mean difference, 15.9%; 95% CI, 3 .8 – 28.1).

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

More and more evidence

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

As reported by Medscape Medical Newsa recent study found that a single infusion of ketamine plus counseling could help alcohol-dependent patients reduce their alcohol consumption.

A separate study showed that a single dose of ketamine plus therapy focused on reactivating “maladaptive reward memories” related to alcohol consumption reduced cravings and alcohol consumption more than either ketamine alone or a placebo infusion alone.

“This ketamine can reduce both alcohol consumption and depression in AUD is therapeutically encouraging,” the researchers write.

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

morgan said Medscape Medical News that ketamine combined with relapse prevention therapy is “currently administered in Awakening clinics in the UK and Norway, but we need to conduct the phase 3 trial in order to make the treatment more widely available. »

An “intriguing new therapy”

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

“Unfortunately, the study showed no difference in alcohol relapse rates, although an improvement in the number of days clean was certainly noteworthy,” Brennan told Medscape Medical News.

“Because this was only a proof-of-concept study and did not compare ketamine to any FDA-approved drug therapy for alcohol, it is still too early to recommend ketamine infusions. people with alcohol use disorders,” he warned.

The study was supported by the Medical Research Council. Morgan received royalties for distributing the KARE therapy license (Ketamine for Alcohol Relapse Reduction). KARE Therapy is licensed by the University of Exeter to Awakn Life Sciences. Morgan has received research funding from Awakn Life Sciences and has consulted for Janssen Pharmaceuticals. Other co-authors disclosed industry connections; the full list can be found with the original article. Brennan did not disclose any relevant financial relationship.

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

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