Open-door policy versus treatment-as-usual in urban psychiatric inpatient wards: a pragmatic, randomised controlled, non-inferiority trial in Norway.

BACKGROUND: Open-door policy is a recommended framework to reduce coercion in psychiatric wards. However, existing observational data might not fully capture potential increases in harm and use of coercion associated with open-door policies. In this first randomised controlled trial, we compared coercive practices in open-door policy and treatment-as-usual wards in an urban hospital setting. We hypothesised that the open-door policy would be non-inferior to treatment-as-usual on the proportion of patients exposed to coercive measures. METHODS: We conducted a pragmatic, randomised controlled, non-inferiority trial comparing two open-door policy wards and three treatment-as-usual acute psychiatric wards at Lovisenberg Diaconal Hospital in Oslo, Norway. An exemption from the consent requirements enabled inclusion and random allocation of all patients admitted to these wards using an open list (2:3 ratio) administrated by a team of ward nurses. The primary outcome was the proportion of patient stays with one or more coercive measures, including involuntary medication, isolation or seclusion, and physical and mechanical restraints. The non-inferiority margin was set to 15%. Primary and safety analyses were assessed using the intention-to-treat population. The trial is registered with ISRCTN registry and is complete, ISRCTN16876467. FINDINGS: Between Feb 10, 2021, and Feb 1, 2022, we randomly assigned 556 patients to either open-door policy wards (n=245; mean age 41·6 [SD 14·5] years; 119 [49%] male; 126 [51%] female; and 180 [73%] admitted to the ward involuntarily) or treatment-as-usual wards (n=311; mean age 41·6 [4·3] years; 172 [55%] male and 138 [45%] female; 233 [75%] admitted involuntarily). Data on race and ethnicity were not collected. The open-door policy was non-inferior to treatment-as-usual on all outcomes: the proportion of patient stays with exposure to coercion was 65 (26·5%) in open-door policy wards and 104 (33·4%) in treatment-as-usual wards (risk difference 6·9%; 95% CI -0·7 to 14·5), with a similar trend for specific measures of coercion. Reported incidents of violence against staff were 0·15 per patient stay in open-door policy wards and 0·18 in treatment-as-usual wards. There were no suicides during the randomised controlled trial period. INTERPRETATION: The open-door policy could be safely implemented without increased use of coercive measures. Our findings underscore the need for more reliable and relevant randomised trials to investigate how a complex intervention, such as open-door policy, can be efficiently implemented across health-care systems and contexts. FUNDING: South-Eastern Norway Regional Health Authority and The Research Council of Norway.

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.

Protocol for the Lovisenberg Open Acute Door Study (LOADS): a pragmatic randomised controlled trial to compare safety and coercion between open-door policy and usual-care services in acute psychiatric inpatients.

INTRODUCTION: The reduction of coercion in psychiatry is a high priority for both the WHO and many member countries. Open-door policy (ODP) is a service model for psychiatric ward treatment that prioritises collaborative and motivational measures to better achieve acute psychiatric safety - and treatment objectives. Keeping the ward main door open is one such measure. Evidence on the impact of ODP on coercion and violent events is mixed, and only one randomised controlled trial (RCT) has previously compared ODP to standard practice. The main objectives of the Lovisenberg Open Acute Door Study (LOADS) are to implement and evaluate a Nordic version of ODP for acute psychiatric inpatient services. The evaluation is designed as a pragmatic RCT with treatment-as-usual (TAU) control followed by a 4-year observational period. METHODS AND ANALYSIS: In this 12-month pragmatic randomised trial, all patients referred to acute ward care will be randomly allocated to either TAU or ODP wards. The primary outcome is the proportion of patient stays with one or more coercive measures. Secondary outcomes include adverse events involving patients and/or staff, substance use and users' experiences of the treatment environment and of coercion. The main hypothesis is that ODP services will not be inferior to state-of-the art psychiatric treatment. ODP and TAU wards are determined via ward-level randomisation. Following conclusion of the RCT, a longitudinal observational phase begins designed to monitor any long-term effects of ODP. ETHICS AND DISSEMINATION: The trial has been approved by the Regional Committees for Medical and Health Research Ethics (REC) in Norway (REC South East #29238), who granted LOADS exemption from consent requirements for all eligible, admitted patients. Data are considered highly sensitive but can be made available on request. Results will be published in peer-reviewed journals and presented at scientific conferences and meetings. TRIAL REGISTRATION NUMBER: ISRCTN16876467. PROTOCOL VERSION: 1.4, 21 December 2021.

The Predictive Value of Degree of Preference for Extended-Release Naltrexone for Treatment Adherence, Opioid Use, and Relapse.

BACKGROUND: Extended-release naltrexone (XR-NTX) is effective for illicit opioid abstinence as an opioid maintenance treatment. To improve treatment outcomes, patient's preference for the modality of treatment is an important factor. OBJECTIVES: We aimed to test the relationship between baseline preference for XR-NTX and adherence to treatment, use of illicit opioids, and risk of relapse. METHODS: In an open-label, Norwegian clinical trial participants with opioid use disorder were randomized to either monthly injections with XR-NTX or daily sublingual buprenorphine-naloxone (BP-NLX) for 12 weeks. Subsequently, participants could continue with their preferred medication in a 36-week follow-up and in a prolonged period of 104 weeks. RESULTS: Of 153 participants who completed detoxification, 72% were men, with a mean age of 36 years. Preference levels were similar across the randomized groups, with no significant associations between preference and adherence to treatment, opioid use, or relapse. The BP-NLX group had a significantly higher risk of first relapse to opioids than the XR-NTX group for all levels of preference (p < 0.001) and a significantly higher number of days of illicit opioid use. In the follow-up period, the adherence rate was twice as high among participants with the highest preference compared to participants with the lowest preference, both among those who switched to XR-NTX and those who continued (hazard ratio 2.2; 1.2-4.0, p = 0.013). Opioid use was significantly higher among participants who switched to XR-NTX with the lowest preference than the medium (p = 0.003) or the highest (p = 0.001) preference. The risk of relapse to opioids, however, was significantly higher among XR-NTX continuing participants with the lowest (p = 0.002) or the medium (p = 0.043) preference than those with the highest preference. CONCLUSIONS: Individuals who matched with their preferred treatment used less illicit opioids than those who did not during short-term treatment. However, baseline preference for XR-NTX treatment primarily influenced longer term opioid use and treatment adherence.

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.

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.

Intact responses to non-drug rewards in long-term opioid maintenance treatment.

Disruption of non-drug reward processing in addiction could stem from long-term drug use, addiction-related psychosocial stress, or a combination of these. It remains unclear whether long-term opioid maintenance treatment (OMT) disrupts reward processing. Here, we measured subjective and objective reward responsiveness in 26 previously heroin-addicted mothers in >7 years stable OMT with minimal psychosocial stress and illicit drug use. The comparison group was 30 healthy age-matched mothers (COMP). Objective reward responsiveness was assessed in a two-alternative forced-choice task with skewed rewards. Results were also compared to performance from an additional 968 healthy volunteers (meta-analytic approach). We further compared subprocesses of reward-based decisions across groups using computational modelling with a Bayesian drift diffusion model of decision making. Self-reported responsiveness to non-drug rewards was high for both groups (means: OMT = 6.59, COMP = 6.67, p = 0.84, BF10 = 0.29), yielding moderate evidence against subjective anhedonia in this OMT group. Importantly, the mothers in OMT also displayed robust reward responsiveness in the behavioral task (t19 = 2.72, p = 0.013, BF10 = 3.98; d = 0.61). Monetary reward changed their task behavior to the same extent as the local comparison group (reward bias OMT = 0.12, COMP = 0.12, p = 0.96, BF10 = 0.18) and in line with data from 968 healthy controls previously tested. Computational modelling revealed that long-term OMT did not even change decision subprocesses underpinning reward behavior. We conclude that reduced sensitivity to rewards and anhedonia are not necessary consequences of prolonged opioid use.

No increased pain among opioid-dependent individuals treated with extended-release naltrexone or buprenorphine-naloxone: A 3-month randomized study and 9-month open-treatment follow-up study.

BACKGROUND AND OBJECTIVES: It is presently unclear whether extended-release naltrexone hydrochloride treatment induces pain or aggravates existing pain among individuals with opioid use disorders. We assessed changes in pain among individuals receiving treatment with either extended-release naltrexone hydrochloride or buprenorphine-naloxone hydrochloride. METHODS: This randomized prospective open-label clinical study included 143 participants (aged 18-60 years) with opioid dependencies, recruited from outpatient addiction clinics at five urban hospitals in Norway. After in-patient detoxification from opioids, patients were randomized to 12-week treatment with either long-acting naltrexone (380 mg intramuscularly injected every four weeks) or buprenorphine-naloxone (flexible 4-16 mg sublingual doses daily). This phase was followed by a 9-month open-treatment study with the participant's choice of either naltrexone or buprenorphine-naloxone. Changes in pain were assessed every 4 weeks using the Norwegian Short-Form of McGill Pain Questionnaire. RESULTS: Throughout the study period, we found no increase in mean sensory pain, affective pain, or present pain intensity on the McGill Pain Questionnaire, in either treatment group, including the subgroups of participants with chronic pain. Participants who switched from buprenorphine-naloxone to extended-release naltrexone treatment after week 12 reported no increase in pain intensity during longer-term treatment. Women experienced significantly more affective pain symptoms than men (p = .01). DISCUSSION AND CONCLUSIONS: Among individuals with opioid use disorder, switching from daily opioid use to long-acting naltrexone did not induce pain, or aggravate mild-to-moderate chronic pain. SCIENTIFIC SIGNIFICANCE: In opioid-dependent individuals, mild-to-moderate chronic pain was not influenced by opioid agonist or antagonist treatment. TRIAL REGISTRATION: Clinicaltrials.gov #NCT01717963, first registered: Oct 28, 2012. Protocol version # 3C, June 12th 2012. (Am J Addict 2018;XX:1-9).

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.

The Norwegian Offender Mental Health and Addiction Study - Design and Implementation of a National Survey and Prospective Cohort Study.

The Norwegian prison inmates are burdened by problems before they enter prison. Few studies have managed to assess this burden and relate it to what occurs for the inmates once they leave the prison. The Norwegian Offender Mental Health and Addiction (NorMA) study is a large-scale longitudinal cohort study that combines national survey and registry data in order to understand mental health, substance use, and criminal activity before, during, and after custody among prisoners in Norway. The main goal of the study is to describe the criminal and health-related trajectories based on both survey and registry linkage information. Data were collected from 1,499 inmates in Norwegian prison facilities during 2013-2014. Of these, 741 inmates provided a valid personal identification number and constitute a cohort that will be examined retrospectively and prospectively, along with data from nationwide Norwegian registries. This study describes the design, procedures, and implementation of the ongoing NorMA study and provides an outline of the initial data.