Review of: Sullivan M et al, Am J Psychiatry 2017; Epub ahead of print.

Study Type: Randomized, open-label, parallel-groups trial

Naltrexone is an opioid blocker that is FDA-approved for the treatment of alcoholism. However, it is also effective off-label for treating opioid use disorder. The medication comes in two forms: an oral pill (brand name ReVia) and an injectable version (XR naltrexone, or Vivitrol). XR naltrexone is composed of 380 mg of naltrexone, given as an intramuscular injection once a month. During that month, patients who try to use opioids will feel little if any high. This works well to prevent relapse if patients keep getting the shot.

However, it is challenging to get patients started on XR naltrexone. If they are actively using, the injection will put them into an immediate and very unpleasant withdrawal. So a common approach is to first give these patients a tapering dose of buprenorphine for a week, and then to wait a second week to completely wash out any last molecules of opioids in their bloodstream. The problem is that this 2-week delay leads to high rates of attrition and relapse, especially in outpatients. In this study, Sullivan and colleagues compared the standard 2-week delay with a rapid 7-day detox protocol using oral naltrexone as a bridge to injectable ­naltrexone.

Researchers recruited 150 patients with opioid dependence from an outpatient research clinic, of which 36.7% were primarily prescription opioid users. Participants, who were mostly male (86%), Caucasian (64%), and around 35 years old (SD 11.4), were randomly assigned to either a 1-week naltrexone detox or a 2-week buprenorphine taper/washout. In both arms, participants didn’t use for 12–24 hours and arrived at the clinic on day 2 in mild to moderate withdrawal. Both treatment arms received up to 8 mg buprenorphine on the first day to ease withdrawal symptoms. The naltrexone group (N = 98) received scheduled doses of clonidine and clonazepam on days 3–8, then oral naltrexone titrated from 1 mg to 25 mg over days 4–7. On day 8, they received a 380 mg injection of XR naltrexone. The buprenorphine group (N = 52) received a typical 7-day buprenorphine taper followed by a 7-day washout period, during which they were given ancillary comfort medications as needed. On day 15, participants who tolerated a 0.8 mg test dose of oral naltrexone received the XR naltrexone shot.

After getting XR naltrexone, participants in both groups received 4 weeks of outpatient treatment, including weekly medical visits, biweekly therapy, and urine toxicology screens at each visit. In the fifth post-induction week, participants were offered a second dose of XR naltrexone and referrals to continue treatment in community programs as warranted.

 

Results
Patients randomized to the 1-week detox were more likely to get the injection without relapsing (56.1% made it) than those in the 2-week detox group (only 32.7% made it). But among those who received XR naltrexone (56), 89.1% of the 1-week group and 82.4% of the 2-week group received a second injection, demonstrating that participants didn’t find the rapid detox aversive enough to refuse the second injection. Overall, 50% of the full naltrexone group received the second injection compared to 26.9% of the buprenorphine group.

 

CATR’s Take
The rapid 1-week naltrexone detox seems to be the better method of getting patients to start the injectable XR naltrexone treatment. Many patients (29%) in the buprenorphine arm relapsed during the 1-week washout period.

 

Practice Implications
If you have opioid-addicted patients who want to try XR naltrexone to prevent relapse, consider this rapid 1-week technique, which allows you to avoid a washout period entirely.