The effectiveness, safety and feasibility of extended-release naltrexone in treatment of opioid dependence: A 12-month clinical study

Abstract

Background: Opioid dependence is a serious and chronic disease which causes global problems. Many opioid users have major psychosocial problems and a high risk of overdose and premature death. Opioid dependence has high costs for the individual user, for their families and for society. Treatment is the most important factor to prevent harmful effects of opioid use. Opioid maintenance treatment (OMT) with opioid agonists: methadone, buprenorphine or buprenorphine-naloxone (BPNLX), may contribute to reduced use of illegal substances and to improved health and social conditions of opioid users. However, opioid maintenance treatment is not a feasible treatment for those who want to achieve abstinence or for other reasons prefer substitution-free treatment. It is therefore important to find other safe and effective treatment options. Long-acting naltrexone given as an intramuscular injection every fourth week (XR-NTX), is a promising treatment option for opioid users. Naltrexone is an opioid antagonist that protects against overdose and blocks the euphoric effects of opioids such as heroin. In addition to reducing the craving for opioids, naltrexone can also reduce craving for alcohol. Naltrexone is not addictive, has few serious side effects and few interactions with other medications. No studies have previously compared XR-NTX with BP-NLX, the recommended substitution medication for opioid maintenance treatment in Norway. Also, there is a lack of studies of longer-term treatment outcomes with XR-NTX in clinical settings where OMT is available at no cost. Study aims: 1. Describe opioid users who volunteer for XR-NTX treatment in a clinical setting where OMT is easily available. 2. Compare effectiveness of XR-NTX and BP-NLX during a 12-week randomised clinical trial (RCT). 3. Evaluate effectiveness, safety and feasibility of XR-NTX in the treatment of opioid dependence during a 48-week period in a clinical setting in Norway. Material and method: In a multi-site clinical trial, n=165 opioid users volunteered for study inclusion and background and demographic data were collected. A total of n=159 participants were randomised to receive either XR-NTX or BP-NLX 1:1 for a 12-week period. Following the randomised clinical trial, participants were given the opportunity to receive XR-NTX or BP-NLX based on their personal preference in a prospective follow-up study for an additional 36 weeks. A number of 117 participants selected XR-NTX and were the subject of investigation in the follow-up study. Participants received an intramuscular injection of XR-NTX every fourth week during the study. Use of opioids and craving for heroin, use of other substances, addiction-related problems, treatment satisfaction, recommendation of treatment and adverse events were assessed at the study attendances. Results: At the time of study inclusion, 37% of the n=165 opioid users who volunteered for the study were not enrolled in OMT, although it was available to them. The volunteers clustered into opioid users in stable recovery and opioid users in ongoing illicit substance use. Of the n=159 participants randomised to the study, n=105 (66%) completed the 12-week RCT. The retention rates were similar in the two randomised groups in the 12-week RCT. In the follow-up study, n=58 (49.6%) of the n=117 participants completed the 36-week period. During the RCT, participants randomised to XR-NTX reported a significantly lower use of opioids and lower craving scores than participants randomised to BP-NLX. No significant differences were found between the two groups regarding use of most other drugs during the RCT. The improvements the participants achieved in the RCT were maintained or further enhanced during the follow-up. Treatment satisfaction was high among XR-NTX participants, and they would to a great extent recommend XR-NTX treatment to others. Adverse effects were most frequently reported during the induction phase of XR-NTX. No new safety concerns were revealed during the one year follow-up. One participant died in an accident, not related to the study medication. Discussion and conclusions: Both opioid users in recovery and opioid users with ongoing severe substance-related problems were attracted to treatment with XR-NTX. We suggest XR-NTX may attract opioid users that prefer abstinence-based treatment and that XR-NTX may increase the overall number of opioid users in treatment. During the 12-week RCT, XR-NTX and BP-NLX showed similar results in retention, effectiveness and safety. The improvements participants achieved in the RCT were maintained or further enhanced during the following 36-week study. Due to the effectiveness and safety shown in this clinical trial during one year, XR-NTX should be considered as one of the treatment modalities available to opioid users in Norway.