TY - JOUR
KW - Administration, Oral
KW - Adult
KW - Buprenorphine, Naloxone Drug Combination/administration & dosage/pharmacokinetics
KW - Delayed-Action Preparations
KW - Diagnostic and Statistical Manual of Mental Disorders
KW - Drug Monitoring/methods
KW - Female
KW - Humans
KW - Injections, Intramuscular
KW - Male
KW - Naloxone/administration & dosage/pharmacokinetics
KW - Narcotic Antagonists/administration & dosage/pharmacokinetics
KW - Opiate Substitution Treatment/methods
KW - Opioid-Related Disorders/diagnosis/drug therapy
KW - Psychiatric Status Rating Scales
KW - Substance Abuse Detection/methods
KW - Treatment Outcome
AU - L. Tanum
AU - K. K. Solli
AU - Z. E. Latif
AU - J. S. Benth
AU - A. Opheim
AU - K. Sharma-Haase
AU - P. Krajci
AU - N. Kunoe
A1 - 
AB - Importance: To date, extended-release naltrexone hydrochloride has not previously been compared directly with opioid medication treatment (OMT), currently the most commonly prescribed treatment for opioid dependence. Objective: To determine whether treatment with extended-release naltrexone will be as effective as daily buprenorphine hydrochloride with naloxone hydrochloride in maintaining abstinence from heroin and other illicit substances in newly detoxified individuals. Design, Setting and Participants: A 12-week, multicenter, outpatient, open-label randomized clinical trial was conducted at 5 urban addiction clinics in Norway between November 1, 2012, and December 23, 2015; the last follow-up was performed on October 23, 2015. A total of 232 adult opioid-dependent (per DSM-IV criteria) individuals were recruited from outpatient addiction clinics and detoxification units and assessed for eligibility. Intention-to-treat analyses of efficacy end points were performed with all randomized participants. Interventions: Randomization to either daily oral flexible dose buprenorphine-naloxone, 4 to 24 mg/d, or extended-release naltrexone hydrochloride, 380 mg, administered intramuscularly every fourth week for 12 weeks. Main Outcomes and Measures: Primary end points (protocol) were the randomized clinical trial completion rate, the proportion of opioid-negative urine drug tests, and number of days of use of heroin and other illicit opioids. Secondary end points included number of days of use of other illicit substances. Safety was assessed by adverse event reporting. Results: Of 159 participants, mean (SD) age was 36 (8.6) years and 44 (27.7%) were women. Eighty individuals were randomized to extended-release naltrexone and 79 to buprenorphine-naloxone; 105 (66.0%) completed the trial. Retention in the extended-release naltrexone group was noninferior to the buprenorphine-naloxone group (difference, -0.1; with 95% CI, -0.2 to 0.1; P = .04), with mean (SD) time of 69.3 (25.9) and 63.7 (29.9) days, correspondingly (P = .33, log-rank test). Treatment with extended-release naltrexone showed noninferiority to buprenorphine-naloxone on group proportion of total number of opioid-negative urine drug tests (mean [SD], 0.9 [0.3] and 0.8 [0.4], respectively, difference, 0.1 with 95% CI, -0.04 to 0.2; P < .001) and use of heroin (mean difference, -3.2 with 95% CI, -4.9 to -1.5; P < .001) and other illicit opioids (mean difference, -2.7 with 95% CI, -4.6 to -0.9; P < .001). Superiority analysis showed significantly lower use of heroin and other illicit opioids in the extended-release naltrexone group. No significant differences were found between the treatment groups regarding most other illicit substance use. Conclusions and Relevance: Extended-release naltrexone was as effective as buprenorphine-naloxone in maintaining short-term abstinence from heroin and other illicit substances and should be considered as a treatment option for opioid-dependent individuals. Trial Registration: clinicaltrials.gov Identifier: NCT01717963.
AD - The Norwegian Centre for Addiction Research, The University of Oslo, Oslo, Norway.; Department.of Research and Development in Mental Health Service, Akershus University Hospital, Lorenskog, Norway.; The Norwegian Centre for Addiction Research, The University of Oslo, Oslo, Norway.; Department.of Research and Development in Mental Health Service, Akershus University Hospital, Lorenskog, Norway.; Institute of Clinical Medicine, Campus Ahus, University of Oslo, Oslo, Norway.; Health Services Research Unit, Akershus University Hospital, Lorenskog, Norway.; Department of Addiction Medicine, Haukeland University Hospital, Haukeland, Norway.; Faculty of Medicine & Odontology, The University of Bergen, Bergen, Norway.; The Norwegian Centre for Addiction Research, The University of Oslo, Oslo, Norway.; Department of Addiction Medicine, Vestfold Hospital Trust, Tonsberg, Norway.; Department of Addiction Medicine, Oslo University Hospital, Oslo, Norway.; The Norwegian Centre for Addiction Research, The University of Oslo, Oslo, Norway.
BT - JAMA psychiatry
C5 - Opioids & Substance Use
CP - 12
CY - United States
DO - 10.1001/jamapsychiatry.2017.3206
IS - 12
JF - JAMA psychiatry
M1 - Journal Article
N2 - Importance: To date, extended-release naltrexone hydrochloride has not previously been compared directly with opioid medication treatment (OMT), currently the most commonly prescribed treatment for opioid dependence. Objective: To determine whether treatment with extended-release naltrexone will be as effective as daily buprenorphine hydrochloride with naloxone hydrochloride in maintaining abstinence from heroin and other illicit substances in newly detoxified individuals. Design, Setting and Participants: A 12-week, multicenter, outpatient, open-label randomized clinical trial was conducted at 5 urban addiction clinics in Norway between November 1, 2012, and December 23, 2015; the last follow-up was performed on October 23, 2015. A total of 232 adult opioid-dependent (per DSM-IV criteria) individuals were recruited from outpatient addiction clinics and detoxification units and assessed for eligibility. Intention-to-treat analyses of efficacy end points were performed with all randomized participants. Interventions: Randomization to either daily oral flexible dose buprenorphine-naloxone, 4 to 24 mg/d, or extended-release naltrexone hydrochloride, 380 mg, administered intramuscularly every fourth week for 12 weeks. Main Outcomes and Measures: Primary end points (protocol) were the randomized clinical trial completion rate, the proportion of opioid-negative urine drug tests, and number of days of use of heroin and other illicit opioids. Secondary end points included number of days of use of other illicit substances. Safety was assessed by adverse event reporting. Results: Of 159 participants, mean (SD) age was 36 (8.6) years and 44 (27.7%) were women. Eighty individuals were randomized to extended-release naltrexone and 79 to buprenorphine-naloxone; 105 (66.0%) completed the trial. Retention in the extended-release naltrexone group was noninferior to the buprenorphine-naloxone group (difference, -0.1; with 95% CI, -0.2 to 0.1; P = .04), with mean (SD) time of 69.3 (25.9) and 63.7 (29.9) days, correspondingly (P = .33, log-rank test). Treatment with extended-release naltrexone showed noninferiority to buprenorphine-naloxone on group proportion of total number of opioid-negative urine drug tests (mean [SD], 0.9 [0.3] and 0.8 [0.4], respectively, difference, 0.1 with 95% CI, -0.04 to 0.2; P < .001) and use of heroin (mean difference, -3.2 with 95% CI, -4.9 to -1.5; P < .001) and other illicit opioids (mean difference, -2.7 with 95% CI, -4.6 to -0.9; P < .001). Superiority analysis showed significantly lower use of heroin and other illicit opioids in the extended-release naltrexone group. No significant differences were found between the treatment groups regarding most other illicit substance use. Conclusions and Relevance: Extended-release naltrexone was as effective as buprenorphine-naloxone in maintaining short-term abstinence from heroin and other illicit substances and should be considered as a treatment option for opioid-dependent individuals. Trial Registration: clinicaltrials.gov Identifier: NCT01717963.
PP - United States
PY - 2017
SN - 2168-6238; 2168-622X
SP - 1197
EP - 1205
EP - 
T1 - Effectiveness of Injectable Extended-Release Naltrexone vs Daily Buprenorphine-Naloxone for Opioid Dependence: A Randomized Clinical Noninferiority Trial
T2 - JAMA psychiatry
TI - Effectiveness of Injectable Extended-Release Naltrexone vs Daily Buprenorphine-Naloxone for Opioid Dependence: A Randomized Clinical Noninferiority Trial
U1 - Opioids & Substance Use
U2 - 29049469
U3 - 10.1001/jamapsychiatry.2017.3206
VL - 74
VO - 2168-6238; 2168-622X
Y1 - 2017
Y2 - Dec 1
ER -