Risk of relapse to non-opioid addictive substances among opioid dependent patients treated with an opioid receptor antagonist or a partial agonist: 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 non-opioid 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.Trial registration clinicaltrials.gov Identifier: NCT01717963