Predischarge Injectable Versus Oral Naltrexone to Improve Postdischarge Treatment Engagement Among Hospitalized Veterans with Alcohol Use Disorder: A Randomized Pilot Proof‐of‐Concept Study

Abstract

Background Injectable naltrexone for alcohol use disorders (AUDs) has been efficacious in several studies. It has not been (1) compared head-to-head with oral naltrexone, or (2) examined in the hospital setting as an intervention that might facilitate treatment attendance after hospital discharge. Methods Fifty-four hospitalized veterans identified as having DSM-IV alcohol dependence were randomized to receive: (1) a 50 mg oral naltrexone plus a 30-day prescription, or (2) a 380 mg intramuscular naltrexone injection prior to discharge. Of 113 veteran inpatients deemed eligible based on screening criteria, 54 met final eligibility criteria and were enrolled and randomized. Baseline data included demographics, alcohol consumption and co-morbidity. Measures of treatment initiation and engagement and alcohol consumption were reassessed at 14-day and 45-day follow ups. Results Thirty-five participants (64.8%) completed the entire study protocol (received a study medication and completed 14- and 45-day follow ups). Among those who received a study medication (n=45), 77.8% completed all follow-up interviews. This pilot study was not designed to have sufficient statistical power for hypothesis testing, and thus, as expected, there were no significant differences between groups in medication adherence (self-report of > 80% of daily doses taken in oral group; receipt of second injection in the injection group), treatment engagement (at least treatment 3 visits in the 30 days post-discharge, and 2 or more visits per month in each of the 3 months following discharge) or alcohol consumption at 14 or at 45 days (p>0.05). The median number of drinks among the entire cohort in the two weeks prior to hospitalization (128 drinks) was significantly higher than at Day 14 (0 drinks, p<0.001) or Day 45 (0 drinks, p<0.001). Rates of medication adherence were 62% in the oral group and 61% in the injection group Conclusions Results indicate feasibility for larger, more definitive study. Both groups had significant reductions in alcohol consumption over time and high treatment engagement rates. Both oral and injectable formulations are feasible to initiate prior to discharge for hospital inpatients identified as having an AUD.

Monitoring and Improving Naltrexone Adherence in Patients with Substance Use Disorder

“…[40][41][42]45,48,62,63 One study assessed the effect of the combination of naltrexone with lofexidine with respect to naltrexone associated with placebo, and found that the combination with lofexidine was favorable with respect to craving control but did not provide improvements in abstinence from opioid use. 63 These results differ from some previously found. 10 In alcohol-consuming patients, despite having adherence rates around 50%, both oral NTX and XR have been shown to be safe and effective drugs in reducing alcohol consumption even in populations with comorbidity.…”

“…Of the studies included in this review, not all found significant differences. 40–42 , 45 , 48 , 62 , 63 One study assessed the effect of the combination of naltrexone with lofexidine with respect to naltrexone associated with placebo, and found that the combination with lofexidine was favorable with respect to craving control but did not provide improvements in abstinence from opioid use. 63 These results differ from some previously found.…”

Novel Agents for the Pharmacological Treatment of Alcohol Use Disorder

“…Oral and injectable naltrexone show similar decreases in likelihood of binge drinking [65] and both are generally well tolerated, with fairly mild side effects [66]. Importantly, however, naltrexone does block the therapeutic effects of opioid analgesics and can precipitate opioid withdrawal in patients who have developed physical dependence to opioids [34]; therefore, individuals who are prescribed naltrexone for AUD must be monitored for opioid use and withdrawal.…”

Evidence-Based Pharmacotherapies for Alcohol Use Disorder

“…28 Similar efficacy between long-acting intramuscular (IM) naltrexone and oral naltrexone has been observed in small proof-of-concept studies, although no large-scale head-tohead comparisons have been performed. 32 Because naltrexone is especially effective in decreasing heavy drinking, it could be considered in highly motivated patients to be taken as needed in settings where they wish to consume alcohol but wish to avoid heavy drinking, although this has been less studied in humans. 33 Naltrexone is dosed 50 mg by mouth once daily or 380 mg via IM injection once monthly.…”