Risk of relapse to non-opioids among patients treated with XR-NTX or BP-NLX: A randomized clinical trial

Background and objective: First study to assess any compensatory increase in use of non-opioid illicit substances
and alcohol in opioid dependent patients randomized to treatment with extended-release naltrexone (XR-NTX) or
buprenorphine-naloxone (BP-NLX) and in longer term treatment with extended-release naltrexone.
Method: A multicenter, outpatient, open-label randomized clinical trial where patients received intramuscular
extended-release naltrexone hydrochloride, 380 mg/month, or daily sublingual buprenorphine-naloxone 8–24/
2–6 mg for 12 weeks, and an option to continue with extended-release naltrexone for an additional 36 week
follow-up. The study was conducted at five urban addiction clinics and detoxification units in Norway between
November 2012, and July 2016.
Results: Among the 143 patients, 106 men and 37 women, there were no significant differences between those
randomized to XR-NTX or BP-NLX in the risk of first relapse to alcohol (HR 1.31; 0.68–2.53), amphetamines (HR
0.88; 0.43–1.80), benzodiazepines (HR 1.24; 0.74–2.09) or cannabis (HR 1.55; 0.83–2.89). Also in the 36-week
(12–48 weeks) follow-up period we found no significant differences between patients continuing with XR-NTX
compared to those switching to XR-NTX after the randomized period in risk of first relapse to any non-opioid
substance. In both study periods, the mean time in the study were longer among those relapsing to nonopioid
addictive substances than those who did not. There was no significant association between first relapse
to illicit opioids and first relapse to non-opioid addictive substances.
Conclusion: There was no increase in the risk of relapse to non-opioid addictive substances neither in short term
nor longer-term treatment with extended-release naltrexone.