Extended-release injectable naltrexone for opioid use disorder: a systematic review

Abstract

Aims: To review systematically the published literature on extended-release naltrexone (XR-NTX, Vivitrol^® ), marketed as a once-per-month injection product to treat opioid use disorder. We addressed the following questions: (1) how successful is induction on XR-NTX; (2) what are adherence rates to XR-NTX; and (3) does XR-NTX decrease opioid use? Factors associated with these outcomes as well as overdose rates were examined.

Methods: We searched PubMed and used Google Scholar for forward citation searches of peer-reviewed papers from January 2006 to June 2017. Studies that included individuals seeking treatment for opioid use disorder who were offered XR-NTX were included.

Results: We identified and included 34 studies. Pooled estimates showed that XR-NTX induction success was lower in studies that included individuals that required opioid detoxification [62.6%, 95% confidence interval (CI) = 54.5-70.0%] compared with studies that included individuals already detoxified from opioids (85.0%, 95% CI = 78.0-90.1%); 44.2% (95% CI = 33.1-55.9%) of individuals took all scheduled injections of XR-NTX, which were usually six or fewer. Adherence was higher in prospective investigational studies (i.e. studies conducted in a research context according to a study protocol) compared to retrospective studies of medical records taken from routine care (6-month rates: 46.7%, 95% CI = 34.5-59.2% versus 10.5%, 95% CI = 4.6-22.4%, respectively). Compared with referral to treatment, XR-NTX reduced opioid use in adults under criminal justice supervision and when administered to inmates before release. XR-NTX reduced opioid use compared with placebo in Russian adults, but this effect was confounded by differential retention between study groups. XR-NTX showed similar efficacy to buprenorphine when randomization occurred after detoxification, but was inferior to buprenorphine when randomization occurred prior to detoxification.

Conclusions: Many individuals intending to start extended-release naltrexone (XR-NTX) do not and most who do start XR-NTX discontinue treatment prematurely, two factors that limit its clinical utility significantly. XR-NTX appears to decrease opioid use but there are few experimental demonstrations of this effect.

Keywords: Extended-release; heroin; injectable; medication-assisted treatment; naltrexone; opioid use disorder; prescription opioids.

Figure 1

PRISMA flow diagram of study selection

Figure 2

Average rates of XR-NTX induction for 15 prospective studies. Numbers above each bar refer to the number of participants for each study (or group) who received their first injection of XR-NTX and the number of participants who were enrolled to receive XR-NTX. * = these studies did not exclude individuals who were actively using opioids but over 90% of participants in these studies did not require opioid detoxification. † = Induction rates significantly different between groups. See “Factors associated with induction” section for more detailed description of detox procedures. ‡ = Statistical comparisons not reported for induction outcomes. PRE and POST refer to whether induction occurred in jail before release (PRE) or in the community after release (POST).

Figure 3

(A) Average rates of adherence at each injection from prospective (n = 15) and retrospective studies (n = 4). Data from three studies (58, 59, 63) are not shown because outcomes were not reported as percentage receiving each injection. (B) Average rates of adherence from prospective (closed circles) and retrospective studies (open circles). Note: Adherence rates shown are only for individuals who received their first XR-NTX injection. Including induction failures when calculating adherence decreases rates substantially (see “Adherence to XR-NTX” in Discussion).