Ketamine infusion may improve alcohol use disorder outcomes

A ketamine infusion improved measures of drinking among individuals with alcohol dependence who were engaged in motivational enhancement therapy, according to results of a randomized controlled pilot trial published in American Journal of Psychiatry.

“Pathological alcohol use leads to an estimated 3.8% of all deaths globally,” Elias Dakwar, MD, of the New York State Psychiatric Institute at Columbia University Medical Center, and colleagues wrote. “Of those in treatment, a large number do not respond to available medications or behavioral treatments. More effective pharmacotherapy options are needed, as well as methods to enhance efforts aimed at behavioral modification.”

Preliminary research suggests ketamine, an N-methyl-D-aspartate receptor antagonist, could help individuals with cocaine dependence maintain abstinence. Dakwar and colleagues noted that because alcohol, cocaine and other drug addictions have comparable clinical challenges and pathophysiology, ketamine may offer similar benefits for individuals with alcohol dependence.

To test this hypothesis, they randomly assigned 40 adults with alcohol dependence (mean age, 53 years; 52.5% women) to a 52-minute, 0.71 mg/kg IV infusion of ketamine (n = 17), or 0.025 mg/kg of the active control midazolam (n = 23). Most participants were white (70.3%), employed (71.8%) and consumed an average of five drinks per day before the study. Ketamine administrations occurred during the second week of a 5-week outpatient regimen of motivational enhancement therapy — a behavioral treatment for several substance use disorders centered around promoting motivation and self-directed change, according to the researchers. They assessed alcohol use after infusion using a timeline followback method and confirmed abstinence through urine ethyl glucuronide testing. To determine daily abstinence from alcohol over the 3-weeks after infusion, they used a longitudinal mixed-effects model.

Results showed a stable model-estimated proportion of abstinence for the ketamine group across the first 3 weeks after infusion compared with a significant decline for the control group. Among those who could be reached by telephone 6 months after the trial, 75% (n = 6) from the ketamine group reported abstinence, compared with 27% (n = 3) from the midazolam group. Further, Dakwar and colleagues found that ketamine delayed the time to relapse and reduced the likelihood of heavy drinking days compared with midazolam. No participants were removed from the study because of adverse events, and infusions were well tolerated.

“The question remains whether a single ketamine infusion would promote abstinence in the long term and whether there is indeed synergy with behavioral treatments,” the researchers wrote. “Further research can build on these promising preliminary findings by replicating this study in a larger sample and with longer follow-up, as well as by more rigorously examining the hypothesis of synergy between ketamine and behavioral treatment.” – by Joe Gramigna

Disclosures: The authors report no relevant financial disclosures.