clinicaltrials.gov Identifier: NCT01717963.

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...

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.

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)