Adjunctive Psychedelic With Relapse Prevention–Based Psychological Therapy in the Treatment of Alcohol Use Disorder

Objective: Early evidence suggests that ketamine may be an effective treatment to sustain abstinence from alcohol. The authors investigated the safety and efficacy of keta- mine 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 clini- cal trial, 96 patients with severe alcohol use disorder were randomly assigned to one of four conditions: 1) three weekly ketamine infusions (0.8mg/kg i.v. over 40 minutes) plus psy- chological 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 [SD510.59]) 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 keta- mine group compared with the placebo group at 6-month follow-up (mean difference510.1%, 95% CI51.1, 19.0), with the greatest reduction in the ketamine plus therapy group compared with the saline plus education group (15.9%, 95% CI53.8, 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.

Am J Psychiatry 2021; 00:1–12; doi: 10.1176/appi.ajp.2021.21030277

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