Ketamine infusions were well-tolerated and associated with fewer days of alcohol use among patients with alcohol use disorder (AUD). These findings, from a placebo-controlled, phase 2 clinical trial, were published in the American Journal of Psychiatry.

Community members (N=96) with moderate to severe AUD who were abstinent from alcohol for 24 hours at baseline were recruited from 2016 to 2019 from 2 sites in the United Kingdom. Participants were randomized in a 1:1:1:1 ratio to receive ketamine and therapy (n=24), ketamine and alcohol education (n=24), placebo and therapy (n=23), or placebo and alcohol education (n=25). Patients were assessed for safety and alcohol consumption for 6 months.

Ketamine was administered as 0.8 mg/kg infusions lasting 40 minutes on visits 2, 4, and 6, spaced 1 to 3 weeks apart. The therapy intervention comprised a mindfulness-based relapse prevention curriculum and was administered in 7 sessions lasting 1.5 hours each. The alcohol education lasted the same amount of time as the therapy intervention and focused on the biology of addiction, the effects of alcohol, and ways to improve healthy living.


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Participants were aged mean 44.1 (standard deviation [SD], 10.6) years, 64% were men, they were consuming 34.7 (SD, 34.3) units of alcohol per week at screening, they had 8.2 (SD, 16.3) previous quit attempts, 46% had a history of anxiety, 42% had a history of depression, and 27% had used ketamine previously.

The average ketamine blood levels at 2 hours after infusion ranged between 60.3 and 66.5 ng/mL.

The recipients of ketamine had 10.1% (95% CI, 1.1%-19.0%) more abstinent days over 6 months compared with placebo recipients. No effect on alcohol relapse at 180 days was observed for ketamine (odds ratio [OR], 0.80; 95% CI, 0.31-2.10).

No significant differences were observed between ketamine plus therapy or education for percentage days abstinent (mean difference, 4.2%; 95% CI, -6.7% to 15.2%) or relapse (OR, 0.75; 95% CI, 0.21-2.65).

Adverse events which were definitely (n=7), probably (n=3), or possibly (n=43) related with the study drug had occurred. No events were serious. A total of 4 events were severe (low mood, hypertension, tachycardia, euphoria).

After the first infusion, 100% of ketamine recipients and 27% of placebo recipients thought they had received ketamine.

This study was limited by the challenges in proper blinding due to the effects of the active study drug.

“In summary, this trial demonstrated that three subanesthetic infusions of ketamine supported abstinence from alcohol […] Overall, the treatment was well tolerated. The data presented here, along with emerging data from other studies of ketamine in AUD, suggest that a further definitive trial is warranted,” concluded the study authors.

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.

Reference

Grabski M, McAndrew A, Lawn W, et al. Adjunctive ketamine with relapse prevention–based psychological therapy in the treatment of alcohol use disorder. Am J Psychiatry. 2022;appiajp202121030277. doi:10.1176/appi.ajp.2021.21030277