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Randomized Controlled Trial
. 2017 May 1;174(5):459-467.
doi: 10.1176/appi.ajp.2016.16050548. Epub 2017 Jan 10.

Long-Acting Injectable Naltrexone Induction: A Randomized Trial of Outpatient Opioid Detoxification With Naltrexone Versus Buprenorphine

Free PMC article
Randomized Controlled Trial

Long-Acting Injectable Naltrexone Induction: A Randomized Trial of Outpatient Opioid Detoxification With Naltrexone Versus Buprenorphine

Maria Sullivan et al. Am J Psychiatry. .
Free PMC article


Objective: At present there is no established optimal approach for transitioning opioid-dependent adults to extended-release injection naltrexone (XR-naltrexone) while preventing relapse. The authors conducted a trial examining the efficacy of two methods of outpatient opioid detoxification for induction to XR-naltrexone.

Method: Participants were 150 opioid-dependent adults randomly assigned 2:1 to one of two outpatient detoxification regimens, naltrexone-assisted detoxification or buprenorphine-assisted detoxification, followed by an injection of XR-naltrexone. Naltrexone-assisted detoxification lasted 7 days and included a single day of buprenorphine followed by ascending doses of oral naltrexone along with clonidine and other adjunctive medications. Buprenorphine-assisted detoxification included a 7-day buprenorphine taper followed by a week-long delay before administration of XR-naltrexone, consistent with official prescribing information for XR-naltrexone. Participants from both groups received behavioral therapy focused on medication adherence and a second dose of XR-naltrexone.

Results: Compared with participants in the buprenorphine-assisted detoxification condition, participants assigned to naltrexone-assisted detoxification were significantly more likely to be successfully inducted to XR-naltrexone (56.1% compared with 32.7%) and to receive the second injection at week 5 (50.0% compared with 26.9%). Both models adjusted for primary type of opioid use, route of opioid administration, and morphine equivalents at baseline.

Conclusions: These results demonstrate the safety, efficacy, and tolerability of low-dose naltrexone, in conjunction with single-day buprenorphine dosing and adjunctive nonopioid medications, for initiating adults with opioid dependence to XR-naltrexone. This strategy offers a promising alternative to the high rates of attrition and relapse currently observed with agonist tapers in both inpatient and outpatient settings.

Trial registration: NCT01377610.

Keywords: Buprenorphine; Detoxification; Injectable Naltrexone; Naltrexone; Opioid Dependence; Outpatient.

Conflict of interest statement


All remaining authors report no financial relationships with commercial interests.


Figure 1
Figure 1
CONSORT diagram of participants in a controlled study of oral naltrexone vs. buprenorphine as detoxification strategies for induction onto extended-release naltrexone in opioid-dependent adults
Figure 2
Figure 2
Longitudinal observed daily proportion of participants with at least mild withdrawal on average (mean Clinical Opiate Withdrawal Scale ≥ 5), by treatment arm (Figure 2A); longitudinal observed daily proportion of participants with at least one report of moderate-severe withdrawal (maximum Clinical Opiate Withdrawal Scale ≥ 12) by treatment arm (Figure 2B).
Figure 3
Figure 3
Longitudinal Clinical Opiate Withdrawal Scale (Figure 3A) and Hamilton Depression Rating Scale (Figure 3B) scores during weeks after XR-naltrexone induction, by treatment arm.a aError bars indicate standard deviation.

Comment in

  • Current Progress in Opioid Treatment.
    Woody GE. Woody GE. Am J Psychiatry. 2017 May 1;174(5):414-416. doi: 10.1176/appi.ajp.2016.16121398. Am J Psychiatry. 2017. PMID: 28457152 No abstract available.

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