No Heavy Drinking Days and Percentage of Days Abstinent in a Randomized Trial of Adjunctive Ketamine for Alcohol Use Disorder: Secondary Analysis of the KARE Trial
Ketamine combined with psychological support may increase days abstinent in adults with alcohol use disorder, but findings should be interpreted with caution due to study limitations.
Where it sits
this study against the rest of the exenatide corpusSummary and findings
This study analyzed data from the KARE trial, focusing on the effects of ketamine combined with psychological support on alcohol use disorder. The trial involved 96 adults who were abstinent following detoxification. Key findings included a 20.7 percentage point difference in days abstinent between treatment groups.
Abstract
In the KARE trial, 96 adults with severe alcohol use disorder, abstinent following detoxification, were randomised in a 2×2 factorial design to 3 weekly infusions of ketamine (0.8 mg/kg) or saline, each combined with mindfulness-based psychological support (PS) or alcohol psychoeducation (PE). We re-expressed the trial data on endpoints acceptable to regulators and compared the most and least intensive arms. Across pooled weeks 17–24, ketamine plus PS gave 78.5% versus 57.8% days abstinent (difference, 20.7 percentage points; P = .032); adjusted for baseline, the difference at weeks 21–24 was 26.9 percentage points (P = .011). At weeks 21–24, 50.0% versus 26.1% had no heavy drinking days (P = .127). Relative reductions in heavy drinking days were 55% in KARE, against 25%, −17%, 46% and 35% reported for naltrexone, exenatide, semaglutide and pemvidutide. These post hoc differences, measured 4 to 6 months after a 4 week course ended, are of magnitude similar to agents requiring continuous administration.
Background
This study addresses the effectiveness of ketamine as an adjunctive treatment for alcohol use disorder, particularly in individuals who are abstinent following detoxification. Previous research has shown varying success rates for pharmacological treatments in this population. Understanding the impact of ketamine in combination with psychological support could provide insights into new treatment strategies.
Methods
The KARE trial employed a 2×2 factorial design involving 96 adults with severe alcohol use disorder. Participants received either 0.8 mg/kg of ketamine or saline, combined with either mindfulness-based psychological support or alcohol psychoeducation. The primary outcomes were days abstinent and heavy drinking days, assessed at multiple time points.
Results
At weeks 17-24, participants receiving ketamine plus psychological support achieved 78.5% days abstinent compared to 57.8% in the control group, with a statistically significant difference of 20.7 percentage points (P = .032). The adjusted difference at weeks 21-24 was 26.9 percentage points (P = .011). However, the difference in heavy drinking days at weeks 21-24 was not statistically significant (P = .127).
Interpretation
The findings suggest that ketamine may enhance abstinence rates when combined with psychological support, although the clinical significance of the differences observed should be carefully considered. The effect size for heavy drinking days was not statistically significant, indicating that while there may be a trend, the results should be interpreted with caution. Limitations such as post hoc analysis and potential confounding factors may affect the reliability of these conclusions.
Key findings
- 78.5% vs 57.8% days abstinent at weeks 17-24, difference 20.7 percentage points, P = .032.
- Adjusted difference at weeks 21-24 was 26.9 percentage points, P = .011.
- 50.0% vs 26.1% had no heavy drinking days at weeks 21-24, P = .127.
- Relative reductions in heavy drinking days were 55% in KARE.
- Naltrexone, exenatide, semaglutide, and pemvidutide reported reductions of 25%, -17%, 46%, and 35% respectively.
Limitations
- Post hoc analysis may not reflect primary outcomes.
- Sample size of 96 may limit generalizability.
- Follow-up duration may be insufficient to assess long-term effects.
- Potential confounding factors not fully addressed.