Ketamine, mindfulness therapy may be effective treatments for alcohol use disorder

Ketamine and mindfulness training may be effective as adjunctive treatments for patients with alcohol use disorder, according to a double-blind, placebo-controlled phase 2 clinical trial published in the American Journal of Psychiatry.

“Depressive symptoms are common in individuals entering treatment for AUD, and the likelihood of alcohol relapse is elevated in patients with such symptoms. Ketamine may support alcohol abstinence by temporarily alleviating depressive symptoms during the high-risk relapse period in the weeks after detoxification,” Meryem Grabski, PhD, of the Psychopharmacology and Addiction Research Centre at the University of Exeter in the U.K., and colleagues wrote

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

Grabski and colleagues sought to compare the safety and impact of ketamine with a placebo to curb cravings and promote abstinence in patients diagnosed with alcohol use disorder (AUD). Additionally, efforts were made to assess the effectiveness of combining mindfulness therapy with ketamine and alcohol education as adjunctive treatments. The trial included 96 patients aged 18 to 65 years who were diagnosed with severe alcohol use disorder. Trial participants were recruited for the study through social media, mainstream media ads, and primary care and secondary care drug and alcohol services. All participants were required to abstain from alcohol for at least 24 hours prior to trial commencement and post a reading of 0.0 on a breath test during the initial trial visit.

The researchers randomly assigned the participants to one of four courses of treatment: one group had three weekly ketamine infusions (0.8mg/kg i.v. over 40 minutes) plus psychological therapy lasting 1.5 hours; a second group had three saline infusions plus psychological therapy; the third group had three ketamine infusions plus alcohol education lasting 1.5 hours; and the final group had three saline infusions plus alcohol education.

Outcomes were based upon self-reported percentage of days without alcohol intake, as well as any relapse during a 6-month follow-up assessment. A monitoring bracelet was placed on each participant on either the first or second of 10 planned visits by clinical personnel and removed by the eighth visit to confirm reportage.

Results showed an overwhelming gap in the difference between the number of abstinent days recorded by the ketamine group compared with the placebo group at the 6-month follow-up (mean difference=10.1%, 95% CI=1.1, 19.0). The greatest reduction in total abstinent days was found when comparing the ketamine plus therapy group with the saline plus education group (15.9%, 95% CI=3.8, 28.1). However, no significant difference was recorded in the rate of relapse between the ketamine and placebo cohorts.

The researchers wrote that no serious adverse effects were reported through administration of the drug by any of the participants.

“That ketamine can reduce both alcohol use and depression in AUD is encouraging therapeutically,” Grabski and colleagues wrote. “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.”