Naltrexone first hit the US market as an oral medication (ReVia) way back in 1984. Over the years, it developed a solid reputation for treating alcoholism and remains a first-line therapy today.

Naltrexone was a bust, however, when it came to treating opioid addiction. Oral naltrexone has been found to be no better than placebo at achieving abstinence from opioids or retaining patients in treatment (Minozzi S et al, Cochrane Database Syst Rev 2011;4:CD001333).

The drug was reformulated as a once-a-month injection after the original patent for the pill expired. This injectable form was FDA-approved in 2006 for treatment of alcoholism under the brand name Vivitrol, and received a second indication for opioid addiction in 2010.

How Does It Work?

Naltrexone is an opioid antagonist with high affinity for the opioid receptor but no intrinsic activity. (Affinity refers to how strongly a drug “sticks” to a receptor, while activity indicates whether the drug “flips the switch” or turns the receptor on. Naltrexone is very sticky but can’t throw the switch.)

Naltrexone has much higher affinity for the opioid receptor than heroin and other opioids that are commonly abused. It thus serves as an opioid “blocker” that prevents opioids from accessing the opioid receptor should patients relapse.

How Is It Dosed?

Vivitrol is supplied in a kit that contains all of the materials needed for one 380 mg injection. Medication is administered as a deep intramuscular injection into the gluteal (buttock) muscle every four weeks.

Patients need to be opioid-free for at least seven days before receiving their first injection to avoid the risk of precipitated opioid withdrawal. Providers might want to first administer a few doses of oral naltrexone to assess tolerability.

Although healthcare providers can stock Vivitrol in their clinics, the cost to maintain inventory is pretty steep—about $1,300 per dose, wholesale cost. Plus there is the risk of medication expiring if kits go unused and/or spoiling if not stored properly. Because of this, some clinics have their patients obtain Vivitrol directly from community pharmacies and then bring it to clinic for administration.

Does It Work?

Virtually all of the data on Vivitrol come from a double-blind clinical trial that was conducted in Russia (Krupitsky E et al, Lancet 2011;377(9776):1506–1533; Krupitsky E et al, Addiction 2013;108(9):1628–1637). Researchers randomized 250 patients to receive either Vivitrol or placebo injections. After six months, the study was unblinded and patients in both groups were offered Vivitrol for another 12 months. Both groups also received counseling.

Fifty-three percent of patients assigned to Vivitrol completed the double-blind phase of the clinical trial, compared to 38% in the placebo arm. Patients receiving Vivitrol had a higher rate of abstinence, greater reduction in cravings, and bigger improvements in self-reported quality of life. Clinicians also judged 86% of the Vivitrol group as “much or very much improved,” versus 58% of placebo patients.

Most of the Vivitrol patients who completed the double-blind portion of the clinical trial continued into the open-label phase of the study. Forty-five percent and 31% of the original cohort were still enrolled at 12 and 18 months, respectively.

How Does It Compare?

Vivitrol hasn’t been compared on a head-to-head basis with methadone (Dolophine, Methadose) or buprenorphine (Subutex, Suboxone, Zubsolv), the current standard of care for treating opioid addiction. (However, a multicenter investigation is currently enrolling patients [http://1.usa.gov/1kdgbCC].) Accordingly, all comparisons involve guesswork.

There are many possible ways to measure success in clinical trials for addiction: self-reported drug use, toxicology, quality of life, and special scales like the Addiction Severity Index. Retention in treatment, however, is the simplest and probably the most powerful. Simply put, patients who remain in treatment generally realize gains in multiple domains, whereas those who stop receiving care usually fare poorly.

Methadone and buprenorphine have similar retention in treatment, although the actual numbers vary from study to study (Farré M et al, Drug Alcohol Depend 2002;65(3):283–290; Connock M et al, Health Technol Assess 2007;11(9):1–171). Data from real world settings (rather than clinical trials) are probably most instructive.

One study, from a methadone clinic in Israel, reported a one-year retention rate of 74% for all participants (Peles E et al, Drug Alcohol Depend 2006;82(3):211–217). At two years, retention rates were 50% for participants who had opioid positive urines and 80% among those who had negative tests. At five years, 40% of those with positive urines and 60% of patients with negative urines were still on program. And, at 10 years, retention in the program was 30% for those who tested positive for opioids and 40% for patients who were opioid negative. These findings are roughly consistent with other long-term cohorts (Strike CJ et al, Addict Behav 2005;30(5):1025–1028; Jimenez-Treviño L et al, Addict Behav 2011;36(12):1184–1190).

Based on these data, I estimate that methadone, and probably buprenorphine, have 20%–30% higher retention in treatment than Vivitrol at one year, and a 10%–20% advantage at two years.

Using Vivitrol in the Real World

My partners and I practice at a federally licensed opioid treatment program at a large urban hospital. As such, opioid addiction is a big chunk of our patient load.

Despite this, we have very few patients on Vivitrol. Virtually every patient who comes to us is actively abusing opioids and requires buprenorphine or methadone for withdrawal suppression. Following stabilization, they generally aren’t interested in tapering off of these medications, which involves some minor discomfort, waiting at least a week, and then switching over to Vivitrol. Frankly, patients don’t see the advantage—and, as their providers, neither do we.

CATR’s Take: Methadone and buprenorphine, which have long, favorable track records, remain the gold standard for treating opioid addiction. Vivitrol has lower retention in treatment but might be a live option in practice environments where buprenorphine and methadone aren’t available or can only be used on a time-limited basis, or for higher-risk populations of patients with substance use disorders, such as healthcare practitioners.