Anxiety, depression, and insomnia in adults with opioid dependence treated with naltrexone vs buprenorphine-naloxone

JAMA Feb 11, 2019

Latif ZH, et al. - In this randomized clinical trial of 159 men and women with opioid dependence, researchers investigated if extended-release naltrexone (XR-NTX) vs opioid agonist treatment unmasked or reinforced current comorbid symptoms of anxiety, depression, or insomnia. Findings revealed an equally effective attenuation of symptoms of anxiety and depression with both drug treatments, but the extended-release naltrexone treatment resulted in a further marked reduction in symptoms of insomnia. Longer-term extended release naltrexone treatment further improved all symptoms. Overall, switching from treatment with an opioid agonist to treatment with XR-NTX should not be prevented due to comorbid symptoms of anxiety, depression, or insomnia in abstinence-motivated persons with opioid dependence.


  • A total of 59 men and women aged 18 to 60 years with opioid dependence were included in this prospective randomized clinical trial conducted at outpatient addiction clinics in 5 urban hospitals in Norway.
  • Researchers randomized participants 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 clinical trial was performed from November 1, 2012, to October 23, 2015.
  • They completed the follow-up study on July 23, 2016.
  • They used an intention-to-treat sample to perform all analyses.
  • The treatment regimen used was: 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.
  • They used the 25-item Hopkins Symptom Checklist and the Insomnia Severity Index to evaluate symptoms of anxiety and depression as well as symptoms of insomnia, respectively, every 4 weeks.


  • Eighty participants were randomized to XR-NTX and 79 to BP-NLX, and 105 participants (66.0%) completed the trial.
  • 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) was reported among the treatment groups.
  • Treatment groups, during clinical trial period, showed no overall differences in terms of 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 XR-NTX group had significantly lower insomnia score (effect size [95% CI], −0.32 [−0.61 to −0.02]; P = .008).
  • Participants continuing with and participants switching to XR-NTX, when observed during follow-up, had no overall differences with regard to 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]).
  • Findings revealed no significant sex differences between the 2 treatment groups.

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