Naltrexone to Prevent Opioid Relapse: A New Weapon in the Fight


There are a few experiences nearly every physician remembers. Delivering that first baby, running that first code, a stranger showing you a rash at a dinner party. Some things are universal. Likewise the first time you injected naloxone into someone suffering from an opioid overdose. For the non-medical folks, naloxone blocks the receptor in the brain that gives opiates their punch. Injecting someone with the stuff essentially puts them into immediate, full-blown withdrawal. It’s lifesaving, but rough. Think that scene from Trainspotting.

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Naltrexone is naloxone’s longer-acting cousin. The oral formulation has a half-life of around four hours, and there have been several studies examining the use of this drug to treat opiate addiction. But overall the results have been disappointing. Skipping a dose is simply too easy.

But we may have a new weapon in the fight against opioid abuse in the form of extended-release naltrexone, a depot injection that lasts roughly a month. A randomized trial appearing in the New England Journal of Medicine examined the efficacy of this agent in a group of previously incarcerated individuals with opioid dependence. Needless to say, this group is at high-risk of relapse.

In this open-label trial, 153 individuals received monthly injections of extended-release naltrexone for six months, and 155 received what you might call usual care (basically counseling and referral to community support programs). The primary outcome was time to relapse – defined, liberally in my opinion, as ten days of self-reported opioid use or two consecutive positive bimonthly urine specimens.

And relapse rates were high – 43% in the extended-release naltrexone group and 64% in the usual care group. Still, that difference translates into a number needed to treat of 5 – meaning this drug is actually pretty efficacious.

Though time to relapse was the primary outcome, I was more interested in some of the ancillary measures. For instance, there was no difference in the re-incarceration rate in the two groups: both were around 25%. Naltrexone has also been advocated as a drug that might curb binge-drinking, but there was no difference in self-reported heavy drinking which occurred in about 15% of both groups.

After six months, naltrexone injections were stopped, but the participants were followed out for a year after that. Without the injections, the relapse rate in the treatment group quickly caught up with the usual care group. This drug may be a long-term proposition.

Knowing the mechanism of action of the drug, it’s not surprising that gastrointestinal side effects were much higher in the treatment group. Fortunately, there were no overdose events in the treatment group, even after treatment ended. This is a critical finding, as there is a theoretical concern that treatment with naltrexone might condition individuals to take higher doses of opioids. When naltrexone is stopped, those higher doses can be fatal. That this effect wasn’t seen should encourage those of us who might want to use this agent in clinical practice.

I should point out that extended-release naltrexone was not compared to what many consider the more standard approach to therapy – namely buprenorphine or methadone maintenance, though that trial is proceeding apace.

In the meantime, this is what we have. And with the epidemic of opioid addiction growing worse by the day, I for one am glad to have one more weapon in the fight.