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
Celia J. A. Morgan, David Nutt
medRxiv September 28, 2026 preprint DOI: 10.64898/2026.09.26.26363761 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Post hoc secondary analysis of a 2x2 factorial randomized controlled trial |
|---|---|
| Sample size | 96 |
| Population | Adults with severe alcohol use disorder, abstinent following detoxification |
| Interventions | Ketamine saline mindfulness-based psychological support (PS) alcohol psychoeducation (PE) |
| Dose | 0.8 mg/kg ketamine, 3 weekly infusions |
| Duration | 4-week course; endpoints at weeks 17-24 and 21-24 (4-6 months after the course ended) |
| Topics | Addiction Esketamine Ketamine |
| Key findings | The authors report that ketamine plus mindfulness-based psychological support produced 78.5% versus 57.8% days abstinent over weeks 17-24 (20.7 percentage point difference; 26.9 points at weeks 21-24 after baseline adjustment) and a 55% relative reduction in heavy drinking days, which they describe as similar in magnitude to reductions reported for naltrexone, exenatide, semaglutide and pemvidutide, despite being measured 4-6 months after a 4-week course. |
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.
In the evidence
This study is part of the evidence base for a synthesis in the library. Here is how each one recorded it.
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Ketamine plus mindfulness-based support gave 78.5% versus 57.8% days abstinent over weeks 17-24 and a 55% relative reduction in heavy drinking days, though the no-heavy-drinking-days difference was not significant.
Synthesized
Comparable studies
Other randomized controlled trials on ketamine for addiction, most cited first.