Naltrexone-Assisted Detox vs Buprenorphine Taper for Opioid Dependence

Researchers compared 2 treatment methods in 150 individuals seeking outpatient treatment for prescription opioid or heroin dependence.

In a randomized controlled trial conducted by researchers at the New York State Psychiatric Institute and Columbia University College of Physicians and Surgeons, an 8-day detoxification process using low-dose oral naltrexone showed superior efficacy to the standard 15-day approach that uses an agonist taper leading to induction with extended-release naltrexone (XR-naltrexone).1

Results from a 2014 survey found that the monthly prevalence of nonmedical prescription opioid and heroin use in the United States was 4.3 million and 435,000, respectively.2 Such estimates, along with the rising rates of opioid overdose and related deaths, highlight the urgent need for effective approaches to detoxification and relapse prevention. Although the US Food and Drug Administration (FDA) has approved XR-naltrexone in injectable form for this purpose, its success is limited by the 7- to 10-day waiting period during which individuals must abstain from opioids prior to receiving the medication.

“This waiting period, combined with conventional methods of opioid detoxification employing agonist tapers over several days, represents a delay of 2 weeks or more before XR-naltrexone can be administered,” wrote the investigators in the present study, which was supported by grants from the National Institute on Drug Abuse (NIDA). Such a long delay is unrealistic in outpatient settings, however, in which greater numbers of patients are seeking treatment as inpatient detoxification beds become increasingly scarce, and the tapered approach has been linked with high relapse and attrition rates.3

While earlier findings suggest that accelerated detoxification methods using buprenorphine and low doses of naltrexone to transition to XR-naltrexone may be effective in outpatient settings, no previous trials have compared such methods with the traditional approach.4 To that end, the current researchers compared 2 treatment methods in 150 individuals seeking outpatient treatment for prescription opioid or heroin dependence.

The rapid treatment included a single day of buprenorphine followed by low doses of naltrexone and adjuvant medications such as clonidine on days 2 to 7, and the standard treatment consisted of a 7-day buprenorphine taper followed by a 7-day waiting period. On day 8 in the first group and day 15 in the second group, patients were administered the initial dose of XR-naltrexone, and all participants who remained in treatment at week 5 received a second dose.

The results demonstrated that rates of XR-naltrexone induction were 56.1% in the rapid naltrexone-assisted group, compared with 32.7% in the buprenorphine-assisted group. In addition, the naltrexone-assisted group was more likely to receive the second dose vs the buprenorphine-assisted group (50% vs 26.9%). Although withdrawal severity and dropout rates were similar between the 2 groups during the first 7 days of treatment, 29% of patients in the standard treatment group relapsed during the 7-day waiting period and thus did not receive XR-naltrexone.

These findings “support the feasibility of ascending low doses of oral naltrexone, in combination with an initial dose of buprenorphine and standing non-opioid ancillary medications, as an outpatient regimen for opioid,” the researchers concluded. “By circumventing the need for a protracted period of abstinence and mitigating the severity of withdrawal symptoms experienced during detoxification, this strategy has the potential to considerably increase patient acceptability of, and access to, antagonist therapy.”

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  1. Sullivan M, Bisaga A, Pavlicova M, et al. Long-acting injectable naltrexone induction: a randomized trial of outpatient opioid detoxification with naltrexone versus buprenorphine [published online January 10, 2017]. Am J Psychiatry. appiajp201616050548. doi: 10.1176/appi.ajp.2016
  2. Center for Behavioral Health Statistics and Quality. Behavioral health trends in the United States: results from the 2014 National Survey on Drug Use and Health. Accessed February 1, 2017.
  3. Day E, Ison J, Strang J. Inpatient versus other settings for detoxification for opioid dependence. Cochrane Database Syst Rev. 2005;(2):CD004580.
  4. Mannelli P, Wu LT, Peindl KS, Swartz MS, Woody GE. Extended release naltrexone injection is performed in the majority of opioid dependent patients receiving outpatient induction: a very low dose naltrexone and buprenorphine open label trial. Drug Alcohol Depend. 2014; 138:83-88. doi: 10.1016/j.drugalcdep.2014.02.002