Anxiety, Depression, and Insomnia Among Adults With Opioid Dependence Treated With Extended-Release Naltrexone vs Buprenorphine-Naloxone

Abstract

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...

Enablers and hindrances for longer-term abstinence in opioid dependent individuals receiving treatment with extended-release naltrexone: A Norwegian longitudinal recovery trial (NaltRec study)

“…The results were consistent with other studies of XR-NTX [ [14] , [15] , [16] , [17] , [18] , [19] , [20] , [21] , [22] ] showing reduced use of opioids and other illicit substances, and an improvement on psychosocial variables [ 13 , [23] , [24] , [25] ]. However, treatment strategies, including treatment with XR-NTX, should include psychosocial support to improve longer-term individual recovery [ 9 , [26] , [27] , [28] ].…”

Adapting treatment length to opioid‐dependent individuals’ needs and preferences: a 2‐year follow‐up to a 1‐year study of extended‐release naltrexone

“…The mean age was 36 years, and 82% were men. Patients’ characteristics were representative of the full patient group enrolled into the parent study [ 12 , 26 , 38 , 40 , 41 ].…”

“…This prospective 2‐year cohort study was a prolonged follow‐up to a previous 3‐month randomized clinical trial comparing XR‐NTX with BP‐NLX [ 26 ] and a subsequent 9‐month follow‐up study of XR‐NTX [ 12 , 38 , 39 , 40 , 41 ]. At the conclusion of the 9‐month follow‐up study, participants were offered continued treatment with XR‐NTX up to a period of 104 weeks.…”

Suicide Risk and Addiction: The Impact of Alcohol and Opioid Use Disorders

“…They include disulfiram, which produces aversive symptoms following alcohol intake; acamprosate, thought to mitigate withdrawal-related symptoms; and naltrexone, a nonselective opiate receptor antagonist that reduces alcohol cravings. These drugs primarily operate by targeting reinforcement mechanisms involved in alcohol misuse; however, extended-release naltrexone has also shown some benefits in reducing attendant anxiety and depressive symptoms [ 116 ].…”

“…Induction of buprenorphine in the emergency room for individuals with OUD who present with opioid overdoses has been shown to decrease the risk for future overdose [ 250 ]. Interestingly, buprenorphine has shown efficacy in treating depressive symptoms during the course of treatment of OUD [ 251 ], as well as in treatment-resistant depression [ 252 – 254 ]. Additionally, buprenorphine has shown promise in reducing suicidal ideation [ 255 , 256 ].…”