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 registrationclinicaltrials.gov Identifier: NCT01717963.

Personal recovery among people with opioid use disorder during treatment with extended-release naltrexone.

Background and aims: Recovery from substance use disorders (SUD) has traditionally been equated with abstinence. "Personal recovery" however emphasizes recovery as a unique and personal process, supported by changes in connectedness, hope, identity, meaning and empowerment. This study aimed to examine personal recovery in people receiving extended-release naltrexone (XR-NTX); specifically investigate changes in personal recovery during treatment, identify groups of participants following distinct trajectories of recovery, and characteristics predicting group-belonging. Methods: Overall change in recovery (Questionnaire about the Process of Recovery, QPR) score was assessed by linear mixed model in a subsample of 135 people with opioid use disorder (OUD) participating in a 24 + 28-week trial of XR-NTX. Growth mixture model was used to identify potential groups of people following distinct trajectories of personal recovery. Results: Overall, there was a significant change in QPR score during treatment. Four groups with distinct recovery trajectories were identified: "initially low- increase" (G1), "initially average- no change" (G2), "initially high- no change" (G3) and "initially high- increase" (G4). The groups were different with regards to level of psychological distress, social support, and the use of benzodiazepines. In addition, previous participation in opioid agonist treatment programs, current pain, life satisfaction, employment, heroin craving and previous use of heroin also differed between groups. Conclusions: Personal recovery among people receiving XR-NTX follows different trajectories, and various factors are associated with personal recovery. Particular attention regarding psychological distress, social support and heroin use among patients commencing XR-NTX treatment is important to facilitate successful recovery trajectories.

Impact of Impulsivity, Hyperactivity, and Inattention on Discontinuation Rate among Opioid-Dependent Patients Treated with Extended-Release Naltrexone.

Previous studies have indicated elevated levels of impulsivity, hyperactivity, and inattention (IHI) among opioid-dependent patients seeking outpatient treatment with extended-release naltrexone (XR-NTX). This led us to hypothesize that IHI may be associated with a higher discontinuation rate for XR-NTX treatment. In a group of 162 patients with opioid dependence, discontinuation prior to the full 24 weeks of the study period (six injections and attending the study visit at 24 weeks) occurred in 49% of the patients, primarily in the early stage of treatment. IHI above the clinical cut-off on the adult ADHD self-report scale (ASRS) was not associated with a risk of premature discontinuation. This finding was not altered when controlling for socio-demographics, substance, use and mental health severity. Conclusively, high levels of IHI per se is not contradictive for XR-NTX treatment in regard to concern for premature discontinuation.

Patients' experiences of continued treatment with extended-release naltrexone: a Norwegian qualitative study.

BACKGROUND: The opioid antagonist extended-release naltrexone (XR-NTX) in the treatment of opioid use disorder (OUD) is effective in terms of safety, abstinence from opioid use and retention in treatment. However, it is unclear how patients experience and adjust to losing the possibility of achieving an opioid effect. This qualitative study is the first to explore how people with opioid dependence experience XR-NTX treatment, focusing on the process of treatment over time. METHODS: Using a purposive sampling strategy, semi-structured interviews were undertaken with 19 persons with opioid use disorder (15 men, four women, 22-55 years of age) participating in a clinical trial of XR-NTX in Norway. The interviewees had received at least three XR-NTX injections. Qualitative content analysis with an inductive approach was used. FINDINGS: Participants described that XR-NTX treatment had many advantages. However they still faced multiple challenges, some of which they were not prepared for. Having to find a new foothold and adapt to no longer gaining an effect from opioids due to the antagonist medication was challenging. This was especially true for those struggling emotionally and transitioning into the harmful use of non-opioid substances. Additional support was considered crucial. Even so, the treatment led to an opportunity to participate in society and reclaim identity. Participants had strong goals for the future and described that XR-NTX enabled a more meaningful life. Expectations of a better life could however turn into broken hopes. Although participants were largely optimistic about the future, thinking about the end of treatment could cause apprehension. CONCLUSIONS: XR-NTX treatment offers freedom from opioids and can facilitate the recovery process for people with OUD. However, our findings also highlight several challenges associated with XR-NTX treatment, emphasizing the importance of monitoring emotional difficulties and increase of non-opioid substances during treatment. As opioid abstinence in itself does not necessarily equal recovery, our findings underscore the importance of seeing XR-NTX as part of a comprehensive, individualized treatment approach. TRIAL REGISTRATION: Clinicaltrials.gov # NCT03647774, first Registered: Aug 28, 2018.

'Not at all what I had expected': Discontinuing treatment with extended-release naltrexone (XR-NTX): A qualitative study.

BACKGROUND: Extended-release naltrexone (XR-NTX), an opioid antagonist, has demonstrated equal treatment outcomes, in terms of safety, opioid use, and retention, to the recommended OMT medication buprenorphine. However, premature discontinuation of XR-NTX treatment is still common and poorly understood. Research on patient experiences of XR-NTX treatment is limited. We sought to explore participants' experiences with discontinuation of treatment with XR-NTX, particularly motivation for XR-NTX, experiences of initiation and treatment, and rationale for leaving treatment. METHODS: We conducted qualitative, semi-structured interviews with participants from a clinical trial of XR-NTX. The study participants (N = 13) included seven women and six men with opioid dependence, who had received a minimum of one and maximum of four injections of XR-NTX. The study team analyzed transcribed interviews, employing thematic analysis with a critical realist approach. FINDINGS: The research team identified three themes, and we present them as a chronological narrative: theme 1: Entering treatment - I thought I knew what I was going into; theme 2: Life with XR-NTX - I had something in me that I didn't want; and theme 3: Leaving treatment - I want to go somewhere in life. Patients' unfulfilled expectations of how XR-NTX would lead to a better life were central to decisions about discontinuation, including unexpected physical, emotional, or mental reactions as well as a lack of expected effects, notably some described an opioid effect from buprenorphine. A few participants ended treatment because they had reached their treatment goal, but most expressed disappointment about not achieving this goal. Some also expressed renewed acceptance of OMT. The participants' motivation for abstinence from illegal substances generally remained. CONCLUSION: Our findings emphasize that a dynamic understanding of discontinuation of treatment is necessary to achieve a long-term approach to recovery: the field should understand discontinuation as a feature of typical treatment trajectories, and discontinuation can be followed by re-initiation of treatment.

Levels of Impulsivity, Hyperactivity, and Inattention and the Association with Mental Health and Substance Use Severity in Opioid-Dependent Patients Seeking Treatment with Extended-Release Naltrexone.

The level of impulsivity, hyperactivity, and inattention (IHI) is higher among patients with substance use disorder (SUD) than in the general population. However, the prevalence of such symptoms in patients seeking treatment with an opioid antagonist, such as extended-release naltrexone (XR-NTX), is unknown. We screened 162 patients with opioid use disorder (OUD) seeking treatment with XR-NTX in Norway using the Adult ADHD Self-Report Scale (ASRS) to estimate the prevalence of IHI alongside an assessment of mental and physical health and substance use. Sixty-six patients scored above the clinical cut-off on the ASRS. Higher levels of IHI were significantly associated with a longer history of frequent amphetamine use, current alcohol use, and greater mental distress. Mental distress was the strongest factor associated with higher levels of IHI. The introduction of screening for IHI and mental distress in opioid maintenance treatment and XR-NTX would likely improve the quality of care and enable clinicians to tailor interventions to the needs of patients with high levels of IHI to prevent treatment discontinuation.

Risk of Relapse Among Opioid-Dependent Patients Treated With Extended-Release Naltrexone or Buprenorphine-Naloxone: A Randomized Clinical Trial.

BACKGROUND AND OBJECTIVES: Compare the risk of relapse to heroin and other illicit opioids among opioid-dependent patients receiving treatment with extended-release naltrexone (XR-NTX) or buprenorphine-naloxone (BP-NLX). METHODS: Re-analyzed data from a 12-week multicenter, open-label, randomized treatment study with a subsequent 36-week open-label follow-up study. All patients, N = 143, had completed detoxification and received at least one dose of study medication. RESULTS: Of 143 patients (72% men), mean age 36 years, 71 received XR-NTX and 72 BP-NLX. The risk of first relapse and the risk of any relapse to heroin and other illicit opioids were both significantly lower in the XR-NTX group compared with the BP-NLX group (hazard ratio [HR], 0.46; 95% confidence interval [CI], 0.28-0.76; P = .002, and HR, 0.11; 95% CI, 0.04-0.29; P < .001, respectively) and (HR, 0.15; 95% CI, 0.09-0.27; P < .001 and HR, 0.05; 95% CI, 0.03-0.09; P < .001, respectively). There was a stable low risk of relapse among participants receiving XR-NTX in the follow-up. DISCUSSION AND CONCLUSIONS: Compared to BP-NLX, patients on XR-NTX had a substantially reduced risk of relapse to illicit opioids and showed a stable low risk of relapse over time in longer-term treatment. SCIENTIFIC SIGNIFICANCE: Our data support XR-NTX as a first-line treatment option for patients with opioid addiction both in short and longer-term treatment. This is the first European study showing that XR-NTX significantly reduces the risk of first and any relapse to heroin use in opioid-dependent patients compared to BP-NLX. Our data contradict previous data from the X:BOT study, showing no significant difference in relapse risk between the groups in a 6-month randomised controlled trial. (© 2021 Authors. The American Journal on Addictions published by Wiley Periodicals LLC on behalf of The American Academy of Addiction Psychiatry). (Am J Addict 2021;30:451-458).

Adapting treatment length to opioid-dependent individuals' needs and preferences: A 2-year follow-up to a 1-year study of extended-release naltrexone.

BACKGROUND AND AIM: Extended-release naltrexone (XR-NTX) is an underused treatment option for opioid dependence, today only available in a few countries in the world. Although effective, safe and feasible in short-term treatment, long-term data are scarce and there is no recommendation for required treatment length. The aims of the study were to determine the perceived need of long-term XR-NTX treatment and to examine long-term treatment outcomes. DESIGN: In this prospective cohort study, following a parent 1-year study of XR-NTX, participants received treatment with XR-NTX at their own discretion for a maximum of 104 weeks. SETTING: Five urban, outpatient addiction clinics in Norway. PARTICIPANTS: Opioid-dependent adults 18-60 years old (n=50) already participating in the parent study. INTERVENTION: XR-NTX administrated as intra-muscular injections (380 mg) every 4 weeks. MEASUREMENTS: Time in the study, use of opioids and other illicit substances, opioid craving, and treatment satisfaction reported every 4 weeks. FINDINGS: Among 58 participants who completed the 1-year parent study, 50 chose to continue the treatment with XR-NTX. Median prolonged treatment time was 44.0 weeks (95% CI: 25.5-62.5), ranging from 8 to 104 weeks. Most participants (35, 70%) reported no relapse to opioid use during treatment while a subgroup (15, 30%) reported relapses to opioids during the study. Scores for mean treatment satisfaction and recommending treatment to others were very high (>9) and mean opioid craving score was very low (<1) on a scale ranging from 0 to 10. CONCLUSIONS: Extended-release naltrexone (XR-NTX) was well tolerated in long-term treatment of opioid dependent individuals in Norway already in XR-NTX treatment. On average, the participants chose to continue treatment for almost 1 year beyond the initial 9 to 12 months of treatment. Participants reported high treatment satisfaction and 70% showed no relapse to opioids during the treatment period.

Discrepancy in Ratings of Shared Decision Making Between Patients and Health Professionals: A Cross Sectional Study in Mental Health Care.

BACKGROUND: A defined goal in mental health care is to increase the opportunities for patients to more actively participate in their treatment. This goal includes integrating aspects of user empowerment and shared decision-making (SDM) into treatment courses. To achieve this goal, more knowledge is needed about how patients and therapists perceive this integration. OBJECTIVE: To explore patient experiences of SDM, to describe differences between patient and therapist experiences, and to identify patient factors that might reduce SDM experiences for patients compared to the experiences of their therapists. METHODS: This cross-sectional study included 992 patients that had appointments with 267 therapists at Sørlandet Hospital, Division of Mental Health during a 1-week period. Both patients and therapists completed the CollaboRATE questionnaire, which was used to rate SDM experiences. Patients reported demographic and treatment-related information. Therapists provided clinical information. RESULTS: The analysis included 953 patient-therapist responder pairs that completed the CollaboRATE questionnaire. The mean SDM score was 80.7 (SD 20.8) among patients, and 86.6 (SD 12.1) among therapists. Females and patients that did not use medication for mental health disorders reported higher SDM scores than males and patients that used psychiatric medications (83.3 vs. 77.7; p < 0.001 and 82.6 vs. 79.8; p = 0.03, respectively). Patients with diagnoses involving psychotic symptoms reported lower SDM scores than all the other patients (66.8 vs. 82.3; p < 0.001). The probability that a patient would report lower SDM scores than their therapist was highest among patients that received involuntary treatment (OR 3.2, p = 0.02), patients with treatment durations longer than 2.2 years (OR 1.9, p = 0.001), and patients that required day care or in-patient care (OR 3.2, p = 0.01 and OR 3.2, p < 0.001, respectively). CONCLUSION: We showed that both therapists and patients reported good SDM experiences in decisional situations, which indicated that SDM was implemented well. However, the SDM scores reported by in-patients and patients with prolonged or involuntary treatments were significantly lower than scores reported by their therapists. Our findings suggested that it remains a struggle in mental health care to establish a common understanding between patients and therapists in decisional processes regarding treatments for some patient groups.

Availability of Extended-Release Naltrexone May Increase the Number of Opioid-Dependent Individuals in Treatment: Extension of a Randomized Clinical Trial.

BACKGROUND AND OBJECTIVE: Opioid maintenance treatment (OMT) is highly available in Norway, but only 50% of opioid-dependent individuals are enrolled in such programs. This study was aimed at examining if availability of extended-release naltrexone (XR-NTX) could attract individuals who for different reasons were not enrolled in an OMT program. METHODS: In a Norwegian clinical study, n = 117 opioid-dependent adults volunteered to receive XR-NTX in a 9-month period, as an extension of a previous randomized clinical trial. RESULTS: Before study inclusion, 40.2% (n = 47) of the study participants were not enrolled in OMT while the remainder were recruited from OMT. Participants not enrolled in OMT displayed more ongoing severe addiction-related problems such as heroin use (p = 0.002), but displayed a higher retention in treatment in the 9-month extension study (p = 0.048 for log-rank test) than participants enrolled in OMT. CONCLUSION: Availability of XR-NTX attracted opioid-dependent individuals not previously enrolled in OMT. While OMT may be perceived as a burden with regard to daily intake and control measures, one-monthly injections with XR-NTX may be perceived favourable, offering more freedom to the patients, not having addictive properties, and potentially reducing heroin craving. We suggest that an introduction of XR-NTX in Europe may increase the number of opioid-dependent individuals in treatment.

Anxiety, Depression, and Insomnia Among Adults With Opioid Dependence Treated With Extended-Release Naltrexone vs Buprenorphine-Naloxone: A Randomized Clinical Trial and Follow-up Study.

Importance: Extended-release naltrexone (XR-NTX) is a promising alternative treatment of opioid addiction but has never been compared with opioid agonist treatment for effects on symptoms of anxiety, depression, and insomnia. Objective: To investigate whether XR-NTX unmasks or reinforces current comorbid symptoms of anxiety, depression, or insomnia compared with opioid agonist treatment. Design, Setting, and Participants: In this prospective randomized clinical trial, 159 men and women aged 18 to 60 years with opioid dependence were randomized to 12 weeks of treatment with either XR-NTX or combined buprenorphine-naloxone (BP-NLX) followed by a 9-month, open-label treatment study with participant choice of 1 of these 2 drugs. The study was conducted at outpatient addiction clinics in 5 urban hospitals in Norway, with the clinical trial performed from November 1, 2012, to October 23, 2015, and the follow-up study completed on July 23, 2016. All analyses were conducted using an intention-to-treat sample. Interventions: Extended-release naltrexone hydrochloride, 380 mg, administered as an injection every 4 weeks or flexible doses (4-24 mg; target dosage 16 mg/d) of daily oral combined BP-NLX. Main Outcomes and Measures: Every 4 weeks, symptoms of anxiety and depression were assessed using the 25-item Hopkins Symptom Checklist, and symptoms of insomnia were assessed using the Insomnia Severity Index. Results: In total, 159 participants were randomized to treatment with either XR-NTX (n = 80) or BP-NLX (n = 79), and 105 participants (66.0%) completed the trial. The treatment groups showed similar distributions of age (mean [SD], 36.4 [8.8] vs 35.7 [8.5] years), sex (61 [76.3%] women and 54 [68.4%] men), and duration of heroin use (mean [SD], 6.9 [5.8] vs 6.7 [5.2] years). For the clinical trial period, no overall differences were detected between treatment groups for anxiety (effect size [95% CI], -0.14 [-0.47 to 0.19]) or depression (effect size [95% CI], -0.12 [-0.45 to 0.21]) scores, but the insomnia score was significantly lower in the XR-NTX group (effect size [95% CI], -0.32 [-0.61 to -0.02]; P = .008). In the follow-up period, no overall differences could be detected in the effect size [95% CI] of scores for anxiety (0.04 [-0.34 to 0.42]), depression (-0.04 [-0.42 to 0.33]), or insomnia (0.04 [-0.33 to 0.42]) between participants continuing with and participants switching to XR-NTX. No significant sex differences between the 2 treatment groups were detected. Conclusions and Relevance: Comorbid symptoms of anxiety, depression, or insomnia in abstinence-motivated persons with opioid dependence should not prevent switching from treatment with an opioid agonist to treatment with XR-NTX. Trial Registration: ClinicalTrials.gov Identifier: NCT01717963.

Effectiveness, safety and feasibility of extended-release naltrexone for opioid dependence: a 9-month follow-up to a 3-month randomized trial.

BACKGROUND AND AIM: This is a follow-up study of a previously published randomized clinical trial conducted in Norway that compared extended-release naltrexone (XR-NTX) to buprenorphine-naloxone (BP-NLX) over 3 months. At the conclusion of the trial, participants were offered their choice of study medication for an additional 9 months. While BP-NLX was available at no cost through opioid maintenance treatment programmes, XR-NTX was available only through study participation, accounting for why almost all participants chose XR-NTX in the follow-up. The aim of this follow-up study was to compare differences in outcome between adults with opioid dependence continuing XR-NTX and those inducted on XR-NTX for a 9-month period, on measures of effectiveness, safety and feasibility. DESIGN: In this prospective cohort study, participants were either continuing XR-NTX, changed from BP-NLX to XR-NTX or re-included into the study and inducted on XR-NTX treatment. SETTING: Five urban, out-patient addiction clinics in Norway. PARTICIPANTS: Opioid-dependent adults continuing (n = 54) or inducted on (n = 63) XR-NTX. INTERVENTION: XR-NTX administrated as intramuscular injections (380 mg) every fourth week. MEASUREMENTS: Data on retention, use of heroin and other illicit substances, opioid craving, treatment satisfaction, addiction-related problems and adverse events were reported every fourth week. FINDINGS: Nine-month follow-up completion rates were 51.9% among participants continuing XR-NTX in the follow-up and 47.6% among those inducted on XR-NTX. Opioid abstinence rates were, respectively, 53.7 and 44.4%. No significant group differences were found in use of heroin and other opioids. CONCLUSIONS: Opioid-dependent individuals who elect to switch from buprenorphine-naltrexone treatment after 3 months to extended-release naltrexone treatment for 9 months appear to experience similar treatment completion and abstinence rates and similar adverse event profiles to individuals who had been on extended-release naltrexone from the start of treatment.

Effectiveness of Injectable Extended-Release Naltrexone vs Daily Buprenorphine-Naloxone for Opioid Dependence: A Randomized Clinical Noninferiority Trial.

Importance: To date, extended-release naltrexone hydrochloride has not previously been compared directly with opioid medication treatment (OMT), currently the most commonly prescribed treatment for opioid dependence. Objective: To determine whether treatment with extended-release naltrexone will be as effective as daily buprenorphine hydrochloride with naloxone hydrochloride in maintaining abstinence from heroin and other illicit substances in newly detoxified individuals. Design, Setting and Participants: A 12-week, multicenter, outpatient, open-label randomized clinical trial was conducted at 5 urban addiction clinics in Norway between November 1, 2012, and December 23, 2015; the last follow-up was performed on October 23, 2015. A total of 232 adult opioid-dependent (per DSM-IV criteria) individuals were recruited from outpatient addiction clinics and detoxification units and assessed for eligibility. Intention-to-treat analyses of efficacy end points were performed with all randomized participants. Interventions: Randomization to either daily oral flexible dose buprenorphine-naloxone, 4 to 24 mg/d, or extended-release naltrexone hydrochloride, 380 mg, administered intramuscularly every fourth week for 12 weeks. Main Outcomes and Measures: Primary end points (protocol) were the randomized clinical trial completion rate, the proportion of opioid-negative urine drug tests, and number of days of use of heroin and other illicit opioids. Secondary end points included number of days of use of other illicit substances. Safety was assessed by adverse event reporting. Results: Of 159 participants, mean (SD) age was 36 (8.6) years and 44 (27.7%) were women. Eighty individuals were randomized to extended-release naltrexone and 79 to buprenorphine-naloxone; 105 (66.0%) completed the trial. Retention in the extended-release naltrexone group was noninferior to the buprenorphine-naloxone group (difference, -0.1; with 95% CI, -0.2 to 0.1; P = .04), with mean (SD) time of 69.3 (25.9) and 63.7 (29.9) days, correspondingly (P = .33, log-rank test). Treatment with extended-release naltrexone showed noninferiority to buprenorphine-naloxone on group proportion of total number of opioid-negative urine drug tests (mean [SD], 0.9 [0.3] and 0.8 [0.4], respectively, difference, 0.1 with 95% CI, -0.04 to 0.2; P < .001) and use of heroin (mean difference, -3.2 with 95% CI, -4.9 to -1.5; P < .001) and other illicit opioids (mean difference, -2.7 with 95% CI, -4.6 to -0.9; P < .001). Superiority analysis showed significantly lower use of heroin and other illicit opioids in the extended-release naltrexone group. No significant differences were found between the treatment groups regarding most other illicit substance use. Conclusions and Relevance: Extended-release naltrexone was as effective as buprenorphine-naloxone in maintaining short-term abstinence from heroin and other illicit substances and should be considered as a treatment option for opioid-dependent individuals. Trial Registration: clinicaltrials.gov Identifier: NCT01717963.

Interest in Extended Release Naltrexone among Opioid Users.

BACKGROUND/AIMS: Treatment for addiction to illicit opioids has, thus far, been limited to 2 main approaches: maintaining physical dependence by administering opioids medically and medication-free abstinence with psychosocial support. Assisted abstinence by taking daily tablets with the opioid antagonist naltrexone is rarely practiced, but it is unclear whether this is due to the limited efficacy of this method or because of user opposition to antagonist medication. Therefore, we wanted to investigate opioid users' interest in antagonist treatment with naltrexone, administered as extended release injection, which supports abstinence by blocking illicit opioids for 4-5 weeks per administration. METHOD: A one-page questionnaire was distributed among opiate users at a broad range of outreach facilities and a total of 731 answered surveys were analysed. RESULTS: More than half of the opioid users in our study were 'very' or 'quite' interested in receiving a 4-weekly opioid-blocking medication for a year (n = 421), while less than a quarter (n = 164) were 'not interested' at all. CONCLUSION: We discovered a high user interest for naltrexone treatment, suggesting that the interest for such treatment was not a barrier to the implementation of extended release naltrexone treatment.

Design of a randomized controlled trial of extended-release naltrexone versus daily buprenorphine-naloxone for opioid dependence in Norway (NTX-SBX).

BACKGROUND: Current guidelines for opioid dependence recommend daily maintenance of physical dependence with methadone or buprenorphine, and discourage abstinence due to the high risk of relapse and overdose. Extended-release formulations of the opioid antagonist naltrexone (XR-NTX) block heroin and other opioid agonists competitively for around 4 weeks per administration. XR-NTX thus enables opioid users to experience abstinence from opioid agonists with greatly reduced risk of overdose compared to medication-free abstinence. While XR-NTX has shown promise compared to placebo and daily naltrexone tablets, there is limited information on long-term safety and its performance compared to daily maintenance treatment. METHODS/DESIGN: In this five-hospital RCT with long-term follow-up, we aim to recruit n = 180 patients in treatment for opioid dependence and allocate them in an open, randomized manner (1:1) to receive either 4-week XR-NTX or daily buprenorphine-naloxone (BP-NLX) for the duration of 12 weeks. Allocation is open-label due to the risk of overdose during attempts to self-unmask allocation using heroin. Urine drug tests are scheduled every week with follow-up visits & assessment every 4 weeks. Primary outcomes are abstinence from illicit opioids in urine drug tests and self-report, as well as retention in treatment. Secondary outcomes include other substance use, injecting behavior, drug craving, mental health, quality of life, treatment satisfaction, abstinence motivation, opioid agonist effect rating, insomnia, and pain. Observation is continued for another 36 weeks in order to assess longer-term safety, adherence and effectiveness. The study is an investigator-initiated trial, funded by public grants and approved by an Independent Ethical Committee (the Regional Ethical Committee for Research South-East B # 2011/1320) and the Norwegian Medicines Agency. DISCUSSION: Despite minor implementation problems, the protocol appears sufficiently robust to generate results of high interest to patients, clinicians and policy makers. TRIAL REGISTRATION: Clinicaltrials.gov # NCT01717963 , first registered: Oct 28, 2012. Protocol version # 3C, June 12th 2012.