XR Naltrexone Acceptable for Opioid Dependence With Comorbid Anxiety, Depression, Insomnia
By Marilynn Larkin
NEW YORK—In abstinence-motivated people with opioid dependence, symptoms of anxiety, depression or insomnia should not prevent switching from an opioid agonist to extended-release naltrexone (XR-NTX), researchers in Norway say.
They had theorized that giving XR-NTX in place of methadone or buprenorphine might "unmask symptoms of psychiatric distress concealed by daily intake of opioids," according to their report online December 19 in JAMA Psychiatry.
Instead, they saw improvements in anxiety, depression, and insomnia within weeks of beginning either study treatment.
"This is the first study to show that treatment with buprenorphine-naloxone (BP-NLX) and XR-NTX were equally effective in reducing symptoms of anxiety and depression, but symptoms of insomnia were significantly more reduced in the XR-NTX group," Drs. Zill-E-Huma Latif and Lars Tanum of Akershus University Hospital said in a joint email.
"Participants continuing on longer term treatment with XR-NTX showed a further improvement in symptoms of anxiety, depression and insomnia over time," they told Reuters Health.
The researchers randomized 159 patients to XR-NTX 380 mg by injection every four weeks or flexible doses (4-24 mg; target dosage 16mg/day) of daily oral BP-NLX. Participants were mostly white; mean age was about 36; 76% were men; and mean duration of heroin use was about 6.8 years.
Participants were followed for nine months, during which they either continued their randomized treatment or switched. Assessments were done every four weeks from baseline to week 48 for anxiety and depression symptoms and insomnia.
Ultimately, 105 patients (66%) completed the trial. No overall differences were detected between treatment groups for anxiety or depression during the trial, but insomnia scores were significantly lower in the XR-NTX group.
During follow-up, no differences were detected in the effect size of scores for anxiety, depression or insomnia between participants continuing with XR-NTX and those switching to it.
Further, there were no significant sex differences between the groups.
"Participants receiving XR-NTX used less illicit opioids and experienced less opioid craving than those receiving buprenorphine-naloxone, (and) this may have influenced the perception of their current anxiety, depression and insomnia symptoms," Drs. Latif and Tanum acknowledged. "However, we found only weak correlations between craving for opioids and anxiety, depression and insomnia scores."
"The anxiety score was not related to the use of heroin," they added, "but both the anxiety and depression scores increased with increasing use of illicit substances, including benzodiazepines and cannabis."
"We have so far not detected any predictors for response to treatment with XR-NTX, and the adherence to treatment or time in the study were not significantly related to the level of anxiety, depression or insomnia scores," they concluded.
Dr. Josh Lichtman, Assistant Medical Director at the Thelma McMillen Center for Alcohol and Drug Treatment at Torrance Memorial Medical Center in California, said the study is "limited," with a small number of participants and "no mention of whether the patients were being treated with any other medications, therapies, or how their substance use disorders were being managed."
Therefore, he told Reuters Health by email, the findings are "not as helpful as they could be."
"I currently treat patients with both of these medications," he noted. "Every patient has their own unique story and situation, so there are lots of factors that psychiatrists must consider when choosing medications," including whether comorbid psychiatric issues are also being treated and whether the patient is engaged in a formal substance-abuse or other community-based program.
"I have seen patients do well on XR-NTX and I have seen patients do well on BP-NLX," he said. "Unfortunately, I have seen the flipside as well, and have seen patients do poorly on each of these and relapse."
"This paper is interesting; however, I would like to see a larger, more detailed study with much stricter inclusion/exclusion criteria," Dr. Lichtman concluded.
JAMA Psychiatry 2018.
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