clinicaltrials.gov Identifier: NCT01717963.

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.

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 PARTICIPANTSIn 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. RESULTSIn 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. 10. Ravndal E, Lauritzen G. Rusmisbruk, angst og depresjon etter 10 år: en prospektiv undersøkelse av stoffmisbrukere med og uten LAR-behandling. Nordic Stud Alcohol and Drugs. 2015;32(5):495-508. 11. Verthein U, Degkwitz P, Haasen C, Krausz M. Significance of comorbidity for the long-term course of opiate dependence. Eur Addict Res. 2005; 11(1...

Background and ObjectivesIt 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.MethodsThis 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.ResultsThroughout 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 ConclusionsAmong 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 SignificanceIn opioid‐dependent individuals, mild‐to‐moderate chronic pain was not influenced by opioid agonist or antagonist treatment.Trial RegistrationClinicaltrials.gov #NCT01717963, first registered: Oct 28, 2012. Protocol version # 3C, June 12th 2012. (Am J Addict 2018;XX:1–9)

BackgroundCurrent 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/DesignIn 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.DiscussionDespite minor implementation problems, the protocol appears sufficiently robust to generate results of high interest to patients, clinicians and policy makers.Trial registrationClinicaltrials.gov # NCT01717963, first registered: Oct 28, 2012. Protocol version # 3C, June 12th 2012.

The authors wish to thank all the participants who shared their stories with us. We also thank the study sites and staff members that helped recruit participants.

Background and aims Extended‐release naltrexone (XR‐NTX) is an under‐used 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 and participants Five urban, outpatient addiction clinics in Norway, comprising opioid‐dependent adults aged 18–60 years (n = 50) already participating in the parent study. Intervention XR‐NTX administered as intramuscular 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% confidence interval (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 9–12 months of treatment. Participants reported high treatment satisfaction and 70% showed no relapse to opioids during the treatment period.

Objective To explore the effects of brief training in Motivational interviewing (MI) for medical students. Design Video recordings of consultations between 113 final-year medical students and simulated patients were scored blind by two independent raters with the Motivational Interviewing Skill Code (MISC). Half of the students participated in a four-hour motivational interviewing workshop while the other half did not. Results Differences between the two groups were statistically significant for five of six global MISC variables. All differences were in the expected direction, with higher scores in the group that had received MI training. There were also statistically significant group differences in the expected direction on several behavioural measures. The group that received MI training asked fewer closed questions and more open questions; they summarized, affirmed and emphasized patient control more often, and directed and confronted less often. Conclusion Four hours of training has a measurable effect on medical students' style and verbal behaviour in simulated patient consultations, but is not sufficient to become proficient in motivational interviewing.