Associations between prescribed benzodiazepines, overdose death and buprenorphine discontinuation among people receiving buprenorphine.
Adolescent
Adult
Aged
Aged, 80 and over
Analgesics, Opioid
/ adverse effects
Benzodiazepines
/ adverse effects
Buprenorphine
/ therapeutic use
Cohort Studies
Drug Overdose
/ mortality
Female
Humans
Male
Massachusetts
Medication Adherence
/ statistics & numerical data
Middle Aged
Opiate Substitution Treatment
/ statistics & numerical data
Opioid-Related Disorders
/ drug therapy
Proportional Hazards Models
Retrospective Studies
Young Adult
benzodiazepines
buprenorphine
buprenorphine discontinuation
cohort study
opioids
overdose
Journal
Addiction (Abingdon, England)
ISSN: 1360-0443
Titre abrégé: Addiction
Pays: England
ID NLM: 9304118
Informations de publication
Date de publication:
05 2020
05 2020
Historique:
received:
04
01
2019
revised:
23
05
2019
accepted:
29
10
2019
pubmed:
10
1
2020
medline:
9
3
2021
entrez:
10
1
2020
Statut:
ppublish
Résumé
Benzodiazepines are commonly prescribed to patients with opioid use disorder receiving buprenorphine treatment, yet may increase overdose risk. However, prescribed benzodiazepines may improve retention in care by reducing buprenorphine discontinuation and thus may prevent relapse to illicit opioid use. We aimed to test the association between benzodiazepine prescription and fatal opioid overdose, non-fatal opioid overdose, all-cause mortality and buprenorphine discontinuation. This was a retrospective cohort study using five individually linked data sets from Massachusetts, United States government agencies. We studied 63 389 Massachusetts residents aged 18 years or older who received buprenorphine treatment between January 2012 and December 2015. Filled benzodiazepine prescription during buprenorphine treatment was the main independent variable. The primary outcome was time to fatal opioid overdose. Secondary outcomes were time to non-fatal opioid overdose, all-cause mortality and buprenorphine discontinuation. We defined buprenorphine discontinuation as having a 30-day gap without another prescription following the end date of the previous prescription. We used Cox proportional hazards models to calculate hazards ratios that tested the association between receipt of benzodiazepines and all outcomes, restricted to periods during buprenorphine treatment. Of the 63 345 individuals who received buprenorphine, 24% filled at least one benzodiazepine prescription during buprenorphine treatment. Thirty-one per cent of the 183 deaths from opioid overdose occurred when individuals received benzodiazepines during buprenorphine treatment. Benzodiazepine receipt during buprenorphine treatment was associated with an increased risk of fatal opioid overdose adjusted hazard ratio (HR) = 2.92, 95% confidence interval (CI) = 2.10-4.06, non-fatal opioid overdose, adjusted HR = 2.05, 95% CI, 1.68-2.50, all-cause mortality, adjusted HR = 1.90, 95% CI, 1.48-2.44 and a decreased risk of buprenorphine discontinuation, adjusted HR = 0.87, 95% CI, 0.85-0.89. Benzodiazepine receipt appears to be associated with both increased risk of opioid overdose and all-cause mortality and decreased risk of buprenorphine discontinuation among people receiving buprenorphine.
Sections du résumé
BACKGROUND AND AIMS
Benzodiazepines are commonly prescribed to patients with opioid use disorder receiving buprenorphine treatment, yet may increase overdose risk. However, prescribed benzodiazepines may improve retention in care by reducing buprenorphine discontinuation and thus may prevent relapse to illicit opioid use. We aimed to test the association between benzodiazepine prescription and fatal opioid overdose, non-fatal opioid overdose, all-cause mortality and buprenorphine discontinuation.
DESIGN AND SETTING
This was a retrospective cohort study using five individually linked data sets from Massachusetts, United States government agencies.
PARTICIPANTS
We studied 63 389 Massachusetts residents aged 18 years or older who received buprenorphine treatment between January 2012 and December 2015.
MEASUREMENTS
Filled benzodiazepine prescription during buprenorphine treatment was the main independent variable. The primary outcome was time to fatal opioid overdose. Secondary outcomes were time to non-fatal opioid overdose, all-cause mortality and buprenorphine discontinuation. We defined buprenorphine discontinuation as having a 30-day gap without another prescription following the end date of the previous prescription. We used Cox proportional hazards models to calculate hazards ratios that tested the association between receipt of benzodiazepines and all outcomes, restricted to periods during buprenorphine treatment.
FINDINGS
Of the 63 345 individuals who received buprenorphine, 24% filled at least one benzodiazepine prescription during buprenorphine treatment. Thirty-one per cent of the 183 deaths from opioid overdose occurred when individuals received benzodiazepines during buprenorphine treatment. Benzodiazepine receipt during buprenorphine treatment was associated with an increased risk of fatal opioid overdose adjusted hazard ratio (HR) = 2.92, 95% confidence interval (CI) = 2.10-4.06, non-fatal opioid overdose, adjusted HR = 2.05, 95% CI, 1.68-2.50, all-cause mortality, adjusted HR = 1.90, 95% CI, 1.48-2.44 and a decreased risk of buprenorphine discontinuation, adjusted HR = 0.87, 95% CI, 0.85-0.89.
CONCLUSIONS
Benzodiazepine receipt appears to be associated with both increased risk of opioid overdose and all-cause mortality and decreased risk of buprenorphine discontinuation among people receiving buprenorphine.
Identifiants
pubmed: 31916306
doi: 10.1111/add.14886
pmc: PMC7156323
mid: NIHMS1057730
doi:
Substances chimiques
Analgesics, Opioid
0
Benzodiazepines
12794-10-4
Buprenorphine
40D3SCR4GZ
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
924-932Subventions
Organisme : NIDA NIH HHS
ID : K23 DA044321
Pays : United States
Organisme : NIAAA NIH HHS
ID : R01 AA021335
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2020 Society for the Study of Addiction.
Références
CMAJ. 2000 Jan 25;162(2):225-33
pubmed: 10674059
Drug Alcohol Depend. 2007 Oct 8;90(2-3):203-9
pubmed: 17478058
Toxicol Sci. 2002 Jan;65(1):107-14
pubmed: 11752690
Eur J Clin Pharmacol. 2012 Mar;68(3):301-9
pubmed: 21927835
Alcohol Alcohol. 2002 Nov-Dec;37(6):609-12
pubmed: 12414556
JAMA. 1990 Nov 21;264(19):2511-8
pubmed: 2232018
Drug Alcohol Depend. 2009 Jan 1;99(1-3):338-44
pubmed: 18824311
Hum Exp Toxicol. 2002 Nov;21(11):599-605
pubmed: 12507255
Pharmacol Rev. 2011 Mar;63(1):243-67
pubmed: 21245208
Patient Prefer Adherence. 2013 Aug 19;7:805-11
pubmed: 23983459
Drug Alcohol Depend. 2017 Jan 01;170:9-16
pubmed: 27865152
J Clin Psychiatry. 2015 Sep;76(9):e1114-21
pubmed: 26455675
Am J Addict. 2010 Jan-Feb;19(1):59-72
pubmed: 20132123
Psychiatr Serv. 2014 Jan 1;65(1):4
pubmed: 24382761
J Clin Psychopharmacol. 2006 Jun;26(3):274-83
pubmed: 16702892
Sleep Med Rev. 2003 Dec;7(6):523-39
pubmed: 15018094
Alcohol Alcohol. 2001 May-Jun;36(3):249-55
pubmed: 11373263
Am J Drug Alcohol Abuse. 2014 Mar;40(2):157-62
pubmed: 24219166
Clin Nurs Res. 2005 Aug;14(3):273-93
pubmed: 15995155
Drug Alcohol Depend. 2017 May 1;174:58-64
pubmed: 28315808
Am J Prev Med. 2018 May;54(5):652-660
pubmed: 29551331
BMC Psychiatry. 2011 May 19;11:90
pubmed: 21595945
Psychiatr Serv. 2018 Jul 1;69(7):832-835
pubmed: 29734918
Psychother Psychosom. 2013;82(6):355-62
pubmed: 24061211
Clin Psychol Rev. 2000 Mar;20(2):149-71
pubmed: 10721495
J Subst Abuse Treat. 2018 Feb;85:90-96
pubmed: 28733097
J Subst Abuse Treat. 2016 Oct;69:64-71
pubmed: 27568512
Drug Alcohol Depend. 2013 Oct 1;132(3):580-6
pubmed: 23688843
J Am Assoc Lab Anim Sci. 2011 Mar;50(2):205-11
pubmed: 21439214
Drug Alcohol Depend. 1981 Nov;8(3):189-99
pubmed: 7327083
Ann Fam Med. 2017 Jul;15(4):355-358
pubmed: 28694272
J Subst Abuse Treat. 2016 Sep;68:57-61
pubmed: 27431047
Am J Orthopsychiatry. 1996 Jan;66(1):17-31
pubmed: 8720638
BMJ. 2017 Apr 26;357:j1550
pubmed: 28446428
Ann Intern Med. 2018 Aug 7;169(3):137-145
pubmed: 29913516
Addiction. 2004 Aug;99(8):978-88
pubmed: 15265095
Forensic Sci Int. 2001 Sep 15;121(1-2):65-9
pubmed: 11516889
Health Aff (Millwood). 2019 Jan;38(1):14-23
pubmed: 30615514
Pharmacoepidemiol Drug Saf. 2017 May;26(5):509-517
pubmed: 28074520
J Addict Med. 2015 Nov-Dec;9(6):470-7
pubmed: 26517324
Addiction. 1998 Sep;93(9):1385-92
pubmed: 9926544
Psychiatr Clin North Am. 2015 Dec;38(4):793-803
pubmed: 26600109
Drug Alcohol Depend. 2005 Jul;79(1):95-101
pubmed: 15943948
J Psychopharmacol. 2017 Jan;31(1):62-66
pubmed: 28072037
J Subst Abuse Treat. 2018 Dec;95:9-17
pubmed: 30352671