Opioid use and dropout from extended-release naltrexone in a controlled trial: implications for mechanism.
Adult
Ambulatory Care
Delayed-Action Preparations
/ therapeutic use
Double-Blind Method
Duration of Therapy
Female
Humans
Male
Naltrexone
/ therapeutic use
Narcotic Antagonists
/ therapeutic use
Opioid-Related Disorders
/ drug therapy
Patient Dropouts
/ statistics & numerical data
Russia
/ epidemiology
Survival Analysis
Treatment Outcome
Dropout
extended-release naltrexone
medication-assisted treatment
opioid dependence
opioid use disorder
relapse
Journal
Addiction (Abingdon, England)
ISSN: 1360-0443
Titre abrégé: Addiction
Pays: England
ID NLM: 9304118
Informations de publication
Date de publication:
02 2020
02 2020
Historique:
received:
03
08
2018
revised:
24
10
2018
accepted:
01
07
2019
pubmed:
18
7
2019
medline:
20
1
2021
entrez:
18
7
2019
Statut:
ppublish
Résumé
Extended-release formulations of naltrexone have emerged as effective treatment options for opioid use disorder. This post-hoc analysis examined the temporal relationship between episodes of opioid use and subsequent dropout in a placebo-controlled trial of extended-release injection naltrexone (XR-NTX) to draw inferences about the mechanism by which extended blockade of opioid receptors translates into clinical effectiveness. This was a 24-week multiple-site, double-blind, randomized trial of monthly XR-NTX versus placebo injections. We analyzed time to dropout from treatment using survival analysis with an extended Cox model as a function of treatment (XR-NTX versus placebo) and with weekly urine drug test (UDT) results for opioids at each week as a time-dependent covariate. Thirteen addiction treatment programs in Russia, 2008-09. A total of 250 adults with opioid use disorder who had completed in-patient detoxification. XR-NTX injection or placebo injection every 4 weeks with weekly clinic visits and biweekly counseling. Urine toxicology for opioids measured weekly and week of dropout from treatment. The Cox model yielded a significant interaction of time-dependent urine toxicology by treatment (P = 0.024). Among patients receiving placebo, a positive UDT in a given week increased the risk for dropout from treatment in the subsequent week [hazard ratio (HR) = 6.25; 95% confidence interval (CI) = 3.6-10.0], whereas among patients receiving XR-NTX, a positive UDT result showed no significant effect on risk for dropout (HR = 1.67; 95% CI = 0.6-4.5). The proportion of patients who completed all 24 weeks without any positive UDT result was 31% on XR-NTX compared with 20% on placebo (P = 0.051). Extended-release injection naltrexone was effective at reducing the risk of dropout from opioid use disorder treatment after an episode of opioid use. Just under a third of patients (31%) on XR-NTX had no opioid-positive urine tests across the trial, but the hypothesis that this would differ from placebo (20%) was not confirmed.
Sections du résumé
BACKGROUND AND AIMS
Extended-release formulations of naltrexone have emerged as effective treatment options for opioid use disorder. This post-hoc analysis examined the temporal relationship between episodes of opioid use and subsequent dropout in a placebo-controlled trial of extended-release injection naltrexone (XR-NTX) to draw inferences about the mechanism by which extended blockade of opioid receptors translates into clinical effectiveness.
DESIGN
This was a 24-week multiple-site, double-blind, randomized trial of monthly XR-NTX versus placebo injections. We analyzed time to dropout from treatment using survival analysis with an extended Cox model as a function of treatment (XR-NTX versus placebo) and with weekly urine drug test (UDT) results for opioids at each week as a time-dependent covariate.
SETTING
Thirteen addiction treatment programs in Russia, 2008-09.
PARTICIPANTS
A total of 250 adults with opioid use disorder who had completed in-patient detoxification.
INTERVENTION
XR-NTX injection or placebo injection every 4 weeks with weekly clinic visits and biweekly counseling.
MEASUREMENTS
Urine toxicology for opioids measured weekly and week of dropout from treatment.
FINDINGS
The Cox model yielded a significant interaction of time-dependent urine toxicology by treatment (P = 0.024). Among patients receiving placebo, a positive UDT in a given week increased the risk for dropout from treatment in the subsequent week [hazard ratio (HR) = 6.25; 95% confidence interval (CI) = 3.6-10.0], whereas among patients receiving XR-NTX, a positive UDT result showed no significant effect on risk for dropout (HR = 1.67; 95% CI = 0.6-4.5). The proportion of patients who completed all 24 weeks without any positive UDT result was 31% on XR-NTX compared with 20% on placebo (P = 0.051).
CONCLUSIONS
Extended-release injection naltrexone was effective at reducing the risk of dropout from opioid use disorder treatment after an episode of opioid use. Just under a third of patients (31%) on XR-NTX had no opioid-positive urine tests across the trial, but the hypothesis that this would differ from placebo (20%) was not confirmed.
Identifiants
pubmed: 31313402
doi: 10.1111/add.14735
pmc: PMC6980175
mid: NIHMS1040942
doi:
Substances chimiques
Delayed-Action Preparations
0
Narcotic Antagonists
0
Naltrexone
5S6W795CQM
Types de publication
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
239-246Subventions
Organisme : NIDA NIH HHS
ID : K24 DA022412
Pays : United States
Organisme : NIDA NIH HHS
ID : UG1 DA013035
Pays : United States
Organisme : Alkermes, Inc.
Pays : International
Commentaires et corrections
Type : CommentIn
Type : CommentIn
Type : CommentIn
Informations de copyright
© 2019 Society for the Study of Addiction.
Références
Psychopharmacology (Berl). 2002 Feb;159(4):351-60
pubmed: 11823887
J Addict Med. 2017 Jan/Feb;11(1):63-69
pubmed: 27898496
NIDA Res Monogr. 1976 Sep;(9):119-22
pubmed: 1004530
Arch Gen Psychiatry. 2009 Oct;66(10):1108-15
pubmed: 19805701
Drug Alcohol Depend. 2015 Feb 1;147:122-9
pubmed: 25555621
Am J Drug Alcohol Abuse. 2016 Sep;42(5):614-620
pubmed: 27436632
Arch Gen Psychiatry. 2006 Feb;63(2):210-8
pubmed: 16461865
J Clin Psychiatry. 1984 Sep;45(9 Pt 2):53-6
pubmed: 6381473
Addict Biol. 2014 Mar;19(2):262-71
pubmed: 22747521
Int J Addict. 1977 Oct;12(7):851-6
pubmed: 201577
Life Sci. 1986 Jul 7;39(1):55-9
pubmed: 2941636
Alcohol Clin Exp Res. 2001 Nov;25(11):1634-47
pubmed: 11707638
Am J Drug Alcohol Abuse. 2011 Jan;37(1):22-6
pubmed: 21192125
JAMA Psychiatry. 2017 Dec 1;74(12):1197-1205
pubmed: 29049469
Arch Gen Psychiatry. 2012 Sep;69(9):973-81
pubmed: 22945623
J Stud Alcohol Drugs. 2012 Mar;73(2):205-15
pubmed: 22333328
J Subst Abuse Treat. 2018 Feb;85:90-96
pubmed: 28733097
Transl Psychiatry. 2015 Mar 17;5:e531
pubmed: 25781230
Exp Clin Psychopharmacol. 2002 Aug;10(3):162-83
pubmed: 12233979
Addiction. 2018 Aug;113(8):1477-1487
pubmed: 29493836
J Psychiatry Neurosci. 2018 Feb 23;43(3):170036
pubmed: 29485031
Exp Clin Psychopharmacol. 2007 Apr;15(2):134-43
pubmed: 17469937
J Addict Med. 2015 May-Jun;9(3):238-43
pubmed: 25901451
Lancet. 2018 Jan 27;391(10118):309-318
pubmed: 29150198
N Engl J Med. 2016 Mar 31;374(13):1232-42
pubmed: 27028913
Am J Drug Alcohol Abuse. 2006;32(4):503-17
pubmed: 17127538
Drug Alcohol Depend. 2015 May 1;150:112-9
pubmed: 25818060
J Subst Abuse Treat. 2006 Dec;31(4):319-28
pubmed: 17084785
Addiction. 2014 Jan;109(1):79-87
pubmed: 23961726
Drug Alcohol Depend. 2013 Nov 1;133(1):80-5
pubmed: 23827259
Lancet. 2011 Apr 30;377(9776):1506-13
pubmed: 21529928
Drug Alcohol Depend. 2013 Oct 1;132(3):674-80
pubmed: 23683793
Cochrane Database Syst Rev. 2014 Feb 06;(2):CD002207
pubmed: 24500948
Am J Med. 1990 Jun;88(6):647-55
pubmed: 2189310
Psychiatr Clin North Am. 2012 Jun;35(2):297-308
pubmed: 22640757
Am J Psychiatry. 2019 Feb 1;176(2):129-137
pubmed: 30336703
J Pharmacol Exp Ther. 2003 Apr;305(1):323-30
pubmed: 12649385
Neuropsychopharmacology. 2016 Aug;41(9):2344-51
pubmed: 26979295
Arch Gen Psychiatry. 2008 Apr;65(4):466-75
pubmed: 18391135