Extended-release vs. oral naltrexone for alcohol dependence treatment in primary care (XON)

Abstract

Background: Extended-release naltrexone (XR-NTX, Vivitrol®) and daily oral naltrexone tablets (O-NTX) are FDA-approved mu opioid receptor antagonist medications for alcohol dependence treatment. Despite the efficacy of O-NTX, non-adherence and poor treatment retention have limited its adoption into primary care. XR-NTX is a once-a-month injectable formulation that offers a potentially more effective treatment option in reducing alcohol consumption and heavy drinking episodes among persons with alcohol use disorders. Methods: This pragmatic, open-label, randomized controlled trial examines the effectiveness of XR-NTX vs. ONTX in producing a Good Clinical Outcome, defined as abstinence or moderate drinking (< 2 drinks/day, men; < 1 drink/day, women; and < 2 heavy drinking occasions/month) during the final 20 of 24 weeks of primary care-based Medical Management treatment for alcohol dependence. Secondary aims will estimate the cost effectiveness of XR-NTX vs. O-NTX, in conjunction with primary-care based Medical Management for both groups, and patient-level characteristics associated with effectiveness in both arms. Alcohol dependent persons are recruited from the community into treatment in a New York City public hospital primary care setting (Bellevue Hospital Center) for 24 weeks of either XR-NTX (n = 117) or O-NTX (n = 120). Results: We describe the rationale, specific aims, design, and recruitment results to date. Alternative design considerations and secondary aims and outcomes are reported. Conclusions: XR-NTX treatment in a primary care setting is potentially more efficacious, feasible, and cost-effective than oral naltrexone when treating community-dwelling persons with alcohol use disorders. This study will estimate XR-NTX’s treatment and cost effectiveness relative to oral naltrexone.

A Retrospective Study of Hospital Recidivism Among Patients with Alcohol Use Disorders Treated with Intramuscular Naltrexone

“…Patients who experience multiple relapses despite high-intensity continuing care may benefit from extended-release naltrexone. An open-label randomized controlled trial examined the effectiveness of extended-release naltrexone versus oral naltrexone for alcohol dependence treatment in primary care [13]. Their conclusion suggests that extended-release naltrexone was potentially more efficacious, feasible, and cost-effective than oral naltrexone when treating community-dwelling persons with alcohol use disorders.…”

Availability of Medications for the Treatment of Alcohol and Opioid Use Disorder in the USA

“…Naltrexone is the most widely used medication for the treatment of alcohol use disorder. Because the oral formulation of naltrexone must be taken daily, patient compliance has been a barrier to its effectiveness [50][51][52][53]. Although the injectable formulation overcomes this barrier, it can be prohibitively expensive (retail cost of $1100 to $1200 per monthly dose) and is more difficult to administer than oral medications [53,54].…”

“…Because the oral formulation of naltrexone must be taken daily, patient compliance has been a barrier to its effectiveness [50][51][52][53]. Although the injectable formulation overcomes this barrier, it can be prohibitively expensive (retail cost of $1100 to $1200 per monthly dose) and is more difficult to administer than oral medications [53,54]. A clinical trial comparing oral naltrexone to extended-release injectable naltrexone for opioid use disorder found twice the rate of treatment retention at 6 months for injectable naltrexone [55].…”

“…A head-to-head trial is currently underway comparing the two medications for alcohol use disorder treatment in primary care settings. Study outcomes will include the probability of a "Good Clinical Outcome" as well as an estimate of the incremental cost-effectiveness of each medication [53].…”

Monitoring and Improving Naltrexone Adherence in Patients with Substance Use Disorder

“… Barriers to adherence included younger age, self-decision, emotional factors, and adverse effects. Yes Yes Malone et al, 2019 50 Randomized controlled trial AUD patients (N =345) To examine the effectiveness of XR-NTX and O-NTX 20–24 weeks O-NTX (N=120) XR-NTX (N=117) XR-NTX in a primary care setting is potentially more efficacious, feasible, and cost-effective than O-NTX*. Yes No Pettinati et al, 2011 56 Randomized controlled trial AUD patients (N = 624) To examined the efficacy of XR-NTX 24 weeks XR-NTX (N=50) PBO (N = 47) XR-NTX was effective in high severity alcohol dependence for both reduction in heavy drinking and maintenance of abstinence, with implications for the role of adherence pharmacotherapy.…”