Extended-Release Naltrexone Improves Psychiatric Disorders During Addiction Therapy

Hands picking at fingers, anxious
Hands picking at fingers, anxious
Changes in anxiety, depression, or insomnia symptoms were examined in patients with opioid use disorder taking extended-release naltrexone or buprenorphine-naloxone.

Extended-release naltrexone (XR-NTX) is as effective as buprenorphine-naloxone (BP-NLX) in improving the symptoms of anxiety, depression, and insomnia in patients being treated for an opioid use disorder, according to study results published in JAMA Psychiatry.

Psychiatric disorders are more common in patients dependent on opioids than in the general population, and are often seen in conjunction with insomnia. Substance use disorder is found in 24% to 43% of patients with anxiety disorders. As anxiety and depression can have a negative impact on the progress of therapy in opioid use disorder, effective treatment of these symptoms is essential. 

Zill-e-Huma Latif, MD, of the department of research and development in mental health, Akershus University Hospital, Norway, and colleagues, conducted a prospective randomized clinical trial in 159 individuals with opioid dependence at outpatient addiction clinics at 5 urban hospitals in Norway from November 1, 2012 to October 23, 2015. They randomly assigned participants age 18 to 60 to 12 weeks of either XR-NTX or BP-NLX followed by a 9-month open-label treatment period. Every 4 weeks, they assessed symptoms of anxiety and depression from baseline to week 48 using the 25-item Hopkins Symptom Checklist and insomnia with the Insomnia Severity Index.

Approximately two-thirds of the patient cohort completed the trial. Demographic variables were similar in both treatment groups, including sex, age, and duration of heroin use. The investigators found no overall differences between the two groups for anxiety (effect size -0.14) or depression (effect size −0.12), but for patients receiving XR-NTX, the insomnia score was significantly lower (effect size −0.32; P =.008). However, during the follow-up period, they found no differences for any of the 3 variables.

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The study is limited by the use of self-report questionnaires to detect the symptoms of depression, anxiety, and insomnia, as individuals’ understanding of questions and rating scales may vary. It is also limited by the failure to test for drug use in the follow-up period.

The investigators suggest that XR-NTX is an effective alternative to BP-NLX for treating anxiety, depression, and insomnia in opioid-dependent patients seeking addiction therapy.  They concluded that “because participants receiving treatment with XR-NTX or BP-NLX showed equal improvements in anxiety, depression, and insomnia as assessed by the [25-item Hopkins Symptom Checklist] and the Insomnia Severity Index, such symptoms should not preclude the choice to leave opioid agonist treatment and to start treatment with XR-NTX.”


Latif ZH, Benth JS, Klemmetsby Solli K, et al. Anxiety, depression, and insominia among adults with opioid dependence treated with extended-release naltrexone vs buprenorphine-naloxone [published online December 19, 2018]. JAMA Psychiatry. doi:10.1001/jamapsychiatry.2018.3537