There is significant support for the efficacy of extended-release naltrexone (XR-NTX) on reducing alcohol use in persons with alcohol use disorders (AUD); however, few persons are offered this medication. Provision of FDA approved effective treatment with medication treatment of XR-NTX should be a priority in order to reduce the harms of AUD.
Alcohol use at all consumption levels increases mortality. Naltrexone (NTX), a US FDA approved and evidence-based pharmacotherapy for treatment of AUD is commercially available in both oral and injectable extended-release formulations [1-4]. Murphy et al. conducted a systematic review and meta-analysis of published studies that evaluated XR-NTX in placebo-controlled trials to assess drinking outcomes [5]. The review included 1254 references with a final assessment of 7 studies, representing over 1500 participants with AUD using XR-NTX in placebo-controlled trials. Importantly, all of the included studies were conducted in outpatient settings and used some form of psychosocial intervention. They found a reduction in drinking days and heavy drinking days, but did not find any difference in relapse. However, those studies that did not require an abstinence lead-in period had a reduction in 2 monthly heavy drinking days, whereas those that did require abstinence had only a reduction of 1.2 monthly heaving drinking days. Further, the trials that lasted 3 or more months found more favorable results with greater reductions in monthly heavy drinking days compared to those that were <3 months.
What does this all mean? The bottom line is that: (i) XR-NTX reduces monthly drinking days and heavy drinking days; (ii) abstinence is not needed to start XR-NTX; and (iii) longer treatment is better (≥3 months). Given the high prevalence of AUDs, it is important to screen for AUD and help patients to reduce their alcohol use [6]—reduction in alcohol use, not just abstinence, is beneficial. Treatment of AUD with XR-NTX is safe even in persons who are actively drinking and in those who have other comorbidities that can affect liver function like HIV, hepatitis C virus, and opioid use disorder (OUD) [7-12]. As Murphy et al. referenced in their article: “a reduction of 1-2 days of heavy drinking is consistent with a 15%–25% of achievable benefit.” [5] Although this analysis did not evaluate long-term outcomes to demonstrate that reduction in alcohol use improves health outcomes, we do know that reduction in alcohol use has been shown to improve mental health symptoms, liver disease, and HIV viral suppression [13-16]. Why are we hesitant to provide a safe medication treatment that could benefit people? There is no special training required to prescribe or administer XR-NTX; it will not precipitate alcohol withdrawal if started while drinking; and it does not cause clinically meaningful elevations in liver function tests. What really is the hesitancy? The reality is that like all substance use disorders (SUDs), stigma of treating people with AUD is profound in the healthcare setting. The placebo-controlled studies in this review by Murphy et al. showed high acceptance of XR-NTX, therefore, demonstrating a willingness by patients to accept treatment. People with the highest level of AUDs, those in justice settings, despite never being informed of the option to treat with XR-NTX in their past, have demonstrated a strong willingness to start XR-NTX for both AUD as well as OUD in other published studies [13, 14, 17]. Additionally, the study by Murphy et al. underscores the point that retention on treatment matters. Their review found that those studies that provided the intervention for 3 or more months had better outcomes. We know in all forms of medication treatment of SUDs that retention on treatment improves outcomes. Therefore, we need to consider ways to help retain people on treatment such as through the use of virtual care sometimes called “telehealth” or “telemedicine,” peer/patient navigators, visiting nurses, and mobile pharmacies.
It is also important to note that most of the participants in the placebo-controlled randomized trials of XR-NTX were men, with few women or racial and ethnic minorities. We need real-world effectiveness studies that evaluate implementation of how to best initiate and retain people on XR-NTX, including populations that have suffered significant inequities in AUD treatment because of racism, gender inequity, housing instability, poverty, transportation constraints, childcare duties, and lack of health insurance. Last, one injection of XR-NTX costs anywhere from $500–$1500. Without Medicaid or universal healthcare, persons typically cannot afford this treatment. Overall there has to be a will to treat AUD in all settings and a way to bring treatment to them—what will it take for all of us to do this?