In the Journals

Buprenorphine-naloxone, naltrexone produce similar improvements in anxiety, depression symptoms

Image of Lars Tanum
Lars Tanum

In a randomized clinical trial and follow-up study, treatment with combined buprenorphine-naloxone demonstrated no advantage over extended-release naltrexone on comorbid symptoms of anxiety, depression or insomnia in abstinence-motivated adults with opioid dependence.

These findings indicate that these symptoms should not prevent patients from starting treatment with extended-release naltrexone after treatment with an opioid agonist, according to researchers.

“Insomnia, anxiety and depressive symptoms are frequently related to opioid abuse or opioid use disorder,” Lars Tanum, MD, PhD, deputy head of the department of research and development in mental health, Akershus University Hospital, Norway, told Healio Psychiatry.

“Previous reports have discussed anhedonia, depression, and reduced pleasure after induction of either extended-release naltrexone or oral naltrexone in such subjects, and among health workers, a perceived opinion that naltrexone will de-mask or worsen symptoms of anxiety, depression and insomnia has developed,” he continued. “We wanted to challenge this perceived opinion by including individuals with such current symptoms in our study.”

In this randomized trial, 159 Norwegian adults with opioid dependence received 12 weeks of treatment with either extended-release naltrexone hydrochloride — administered as a 380-mg injection every 4 weeks or flexible doses (4 mg to 24 mg; target dosage 16 mg per day) — or daily oral combined buprenorphine-naloxone. This was followed by a 9-month, open-label, follow-up study in which participants chose to receive one of these two drugs.

The researchers examined symptoms of anxiety and depression via the 25-item Hopkins Symptom Checklist, and symptoms of insomnia via the Insomnia Severity Index, every 4 weeks.

Overall, 80 participants received extended-release naltrexone, 79 received buprenorphine-naloxone and 105 completed the trial. Researchers observed no differences between treatment groups in scores of anxiety (effect size = –0.14; 95% CI, –0.47 to 0.19) and depression (effect size = –0.12; 95% CI, –0.45 to 0.21). However, the mean insomnia score was significantly lower among participants receiving extended-release naltrexone (effect size = –0.32; 95% CI, –0.65 to 0.02).

During the follow-up study, Tanum and colleagues saw no differences overall in anxiety (effect size = 0.04; 95% CI, –0.34 to 0.42), depression (effect size = –0.04; 95% CI, –0.42 to 0.33), or insomnia scores (effect size = 0.04; 95% CI, –0.33 to 0.42) between participants who continued extended-release naltrexone after the trial ended and those who switched from buprenorphine-naloxone to extended-release naltrexone after week 12.

In addition, analyses revealed no overall differences according to sex in trends of anxiety, depression or insomnia between groups. Both treatment groups also exhibited reductions in illicit opioid and other illegal substance use.

“Comorbid symptoms of anxiety, depression or insomnia in opioid-dependent individuals should not preclude the choice to leave opioid agonist treatment or prevent switching from opioid agonist treatment to long-acting naltrexone in abstinence-motivated individuals,” Tanum said. – by Savannah Demko

Disclosure: The authors report no relevant financial disclosures.

Image of Lars Tanum
Lars Tanum

In a randomized clinical trial and follow-up study, treatment with combined buprenorphine-naloxone demonstrated no advantage over extended-release naltrexone on comorbid symptoms of anxiety, depression or insomnia in abstinence-motivated adults with opioid dependence.

These findings indicate that these symptoms should not prevent patients from starting treatment with extended-release naltrexone after treatment with an opioid agonist, according to researchers.

“Insomnia, anxiety and depressive symptoms are frequently related to opioid abuse or opioid use disorder,” Lars Tanum, MD, PhD, deputy head of the department of research and development in mental health, Akershus University Hospital, Norway, told Healio Psychiatry.

“Previous reports have discussed anhedonia, depression, and reduced pleasure after induction of either extended-release naltrexone or oral naltrexone in such subjects, and among health workers, a perceived opinion that naltrexone will de-mask or worsen symptoms of anxiety, depression and insomnia has developed,” he continued. “We wanted to challenge this perceived opinion by including individuals with such current symptoms in our study.”

In this randomized trial, 159 Norwegian adults with opioid dependence received 12 weeks of treatment with either extended-release naltrexone hydrochloride — administered as a 380-mg injection every 4 weeks or flexible doses (4 mg to 24 mg; target dosage 16 mg per day) — or daily oral combined buprenorphine-naloxone. This was followed by a 9-month, open-label, follow-up study in which participants chose to receive one of these two drugs.

The researchers examined symptoms of anxiety and depression via the 25-item Hopkins Symptom Checklist, and symptoms of insomnia via the Insomnia Severity Index, every 4 weeks.

Overall, 80 participants received extended-release naltrexone, 79 received buprenorphine-naloxone and 105 completed the trial. Researchers observed no differences between treatment groups in scores of anxiety (effect size = –0.14; 95% CI, –0.47 to 0.19) and depression (effect size = –0.12; 95% CI, –0.45 to 0.21). However, the mean insomnia score was significantly lower among participants receiving extended-release naltrexone (effect size = –0.32; 95% CI, –0.65 to 0.02).

During the follow-up study, Tanum and colleagues saw no differences overall in anxiety (effect size = 0.04; 95% CI, –0.34 to 0.42), depression (effect size = –0.04; 95% CI, –0.42 to 0.33), or insomnia scores (effect size = 0.04; 95% CI, –0.33 to 0.42) between participants who continued extended-release naltrexone after the trial ended and those who switched from buprenorphine-naloxone to extended-release naltrexone after week 12.

In addition, analyses revealed no overall differences according to sex in trends of anxiety, depression or insomnia between groups. Both treatment groups also exhibited reductions in illicit opioid and other illegal substance use.

“Comorbid symptoms of anxiety, depression or insomnia in opioid-dependent individuals should not preclude the choice to leave opioid agonist treatment or prevent switching from opioid agonist treatment to long-acting naltrexone in abstinence-motivated individuals,” Tanum said. – by Savannah Demko

Disclosure: The authors report no relevant financial disclosures.

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