Efficacy of Extended-Release Naltrexone in Alcohol-Dependent Patients Who Are Abstinent Before Treatment

Abstract

Extended-release naltrexone (XR-NTX) is a once-a-month injectable formulation that is Food and Drug Administration-approved for the treatment of alcohol dependence in patients able to abstain from alcohol before treatment initiation. This paper presents the results of an analysis of efficacy data from a subgroup of patients with 4 days or more of voluntary abstinence before treatment initiation (n = 82) on a wide range of drinking-related outcomes. In these patients, all of whom received counseling, the rate of abstinence was severalfold higher for XR-NTX 380 mg compared with placebo: median time to first drink was 41 days versus 12 days, respectively; rate of continuous abstinence at end of the study was 32% versus 11% (P = 0.02). Extended-release naltrexone 380 mg, compared with placebo, substantially increased time to first heavy drinking event (>180 days vs 20 days; P = 0.04) and decreased the median number of any drinking days per month by 90% (0.7 vs 7.2; P = 0.005) and heavy drinking days per month by 93% (0.2 days vs 2.9 days; P = 0.007). The XR-NTX 380 mg group also had more than twice as many responders compared with placebo (70% vs 30%; P = 0.006; responder defined as having no more than 2 heavy drinking days in any consecutive 28-day period) and experienced greater improvement in gamma-glutamyl transpeptidase levels (P = 0.03). Outcomes for XR-NTX 190 mg (n = 26) were generally intermediate, demonstrating a dose-response effect. In conclusion, XR-NTX 380 mg prolonged abstinence and reduced the number of heavy drinking days and drinking days in patients who were abstinent for as few as 4 days before treatment initiation.

Adoption of Injectable Naltrexone in U.S. Substance Use Disorder Treatment Programs

“…Studies of the effi cacy of injectable naltrexone in treating AUD patients indicate that it reduces drinking days, median drinks per day, and number of heavy drinking days and increases abstinence rates, percentage of days abstinent, length of continuous abstinence, time to fi rst drink, and time to fi rst heavy drinking day (Garbutt et al, 2005;Gastfriend et al, 2005;Kranzler et al, 2004;Lee et al, 2012;O'Malley et al, 2007). Recent meta-analyses of studies assessing injectable naltrexone's effectiveness indicate that its use in AUD patients is linked to a reduction in heavy drinking days (Jonas et al, 2014), longer refi ll persistence, and longer medication persistence compared with acamprosate (Campral) and tablet naltrexone (Hartung et al, 2014).…”

Case Report of Severe Injection Site Reaction Associated with Intramuscular Naltrexone

“…Another trial found that injectable naltrexone increased time to first drinking day but did not have an effect on time to first heavy drinking day (Kranzler et al, 2004). One trial found that only patients who were abstinent from alcohol before treatment showed a benefit (O'Malley et al, 2007). Furthermore, a recent trial demonstrated fewer drinks per day, fewer drinking days per month and decreased rates of heave drinking days (Lee et al, 2010) One of the largest trials evaluating the efficacy of injectable naltrexone was the COMBINE trial, which evaluated the effect of injectable naltrexone in combination with behavioral intervention, acamprosate, or both.…”

The Role of Delta Opioid Receptors in Ethanol Consumption and Seeking: Implications for New Treatments for Alcohol Use Disorders

“…More recently, the use of naltrexone in an extendedrelease intra-muscular (i.m.) depot formulation (Vivitrol  ) is more effective in patients who are able to abstain from drinking prior to treatment (O'Malley et al, 2007;Pettinati et al, 2009). Taken together, treatment with naltrexone appears to have the most consistent effects on drinking outcomes in subjects with A118G mutation.…”