Single-dose intravenous ketamine or intramuscular naltrexone for high-utilization inpatients with alcohol use disorder: pilot trial feasibility and readmission rates

Abstract

Background Alcohol use disorder (AUD) accounts for millions of acute care encounters annually in the United States. Hospitalization represents a vital opportunity to intervene pharmacologically, but low medication adherence is a significant barrier. Two single-dose, adherence-independent interventions are well suited for pre-discharge administration: intravenous (IV) ketamine and intramuscular (IM) naltrexone. Their feasibility and readmission-reducing efficacy in hospital settings are not well-established. Methods A 3-arm, open-label randomized trial was conducted at our safety-net medical hospital among high-utilization inpatients with severe AUD. Consented adults (age 18–65) were randomized to (1) IV ketamine (KET) 0.5 mg/kg over 40 min, (2) IM naltrexone (NTX) 380 mg once, or (3) linkage alone (LA). The primary clinical outcome was 30-day all-cause hospital readmission rate. All were provided enhanced linkage to outpatient addiction clinic. Results We consented and randomized 44 participants (n = 13, 14, 17 for KET, NTX, LA, respectively), with a mean of 3.2 past-year hospitalizations. Compared to the LA arm, both the KET arm (RR 0.37, p = 0.17) and NTX arm (RR 0.52, p = 0.27) had a lower 30-day readmission rate, though the differences were nonsignificant. Immediate acceptability ratings of KET and NTX were 9.50 and 9.17 out of 10, respectively. No serious adverse events or illicit ketamine use was reported. Conclusions Both interventions are feasible and showed promise in reducing readmissions for high-utilization AUD inpatients. Despite randomization, baseline characteristics may have differed in ways that biased against the control arm. Additional pragmatic studies—with larger sample size, blinding, and robust follow-up data collection—are needed to verify findings and better understand mediating factors. ClinicalTrials.gov Identifier NCT04562779. Registered 24 September 2020. https://clinicaltrials.gov/ct2/show/NCT04562779

Outcomes After Initiation of Medications for Alcohol Use Disorder at Hospital Discharge

“…Although more than 20% of readmissions occur at different hospitals, neither prior study evaluated health care use at other health systems. 34 An open-label pilot trial 35 found a 48% relative reduction in 30-day readmissions among patients randomized to injectable naltrexone compared with linkage to care alone. These underpowered results did not reach statistical significance but reflect a similar magnitude of effect size as observed in our study.…”

Ketamine for Adults With Substance Use Disorders

“…The primary study by Terasaki et al (2022) 18 was a 3-arm open-label RCT involving 44 adult patients with severe AUD, who had been hospitalized in the previous year. The authors did not calculate sample size to detect a hypothesized treatment difference between groups.…”

“…Appendix 2 provides details regarding the characteristics of 2 included SRs 16,17 (Table 2), and 1 primary study 18 (Table 3).…”

“…Patients in the relevant studies included in the SR by Kelson et 18 were adults with severe AUD, who had been hospitalized in the previous year. The mean age was 45.1 years.…”

“…The included primary study by Terasaki et al (2022) 18 compared IV ketamine (0.5 mg/kg over 40 minute) versus IM naltrexone (380 mg once) versus linkage alone (i.e., no pharmacological intervention, but patients still received outpatient addiction clinic linkage and the research stipends).…”