5 Benzodiazepine – Opioid Coprescribing
Table of Contents
5.6 Adverse Outcomes: Overall 7
5.7 Adverse Outcomes: By Organ System.. 8
5.8 Adverse Outcomes: General Function. 9
5.9 Adverse Outcomes: Executive Function. 10
5.10 Adverse Outomes: Non-medical Use. 11
5.11 Benzodiazepines + Opioids in Subpopulations. 12
See also
Benzodiazepine +/- Opioid Overdose
Benzodiazepine Pain
5.1 Reviews |
Expert Opinion
Parhami I, Massey J, Trimzi I, et al. Risks associated with co-prescribing opioids and benzodiazepines and Delaware’s Prescription Drug Monitoring Program. Del Med J. 2015;87(9):270-4. Link Link
Sullivan MD. What are we treating with opioid and sedative-hypnotic combination therapy? Pharmacoepidemiol Drug Saf. 2015;24(8):893-5. Link
Webster LR, Reisfield GM, Dasgupta N. Eight principles for safer opioid prescribing and cautions with benzodiazepines. Postgrad Med. 2015;127(1):27-32. Abstract
Guidelines
American Pain Society 2014 Methadone Safety: A Clinical Practice Guideline
American Society of Clinical Oncology 2016 Management of Chronic Pain in Survivors of Adult Cancers
CDC 2016 CDC guideline for Prescribing Opioids for Chronic Pain – United States, 2016
Chou R, Gordon DB, de Leon-Casasola OA, et al. Management of postoperative pain: a clinical practice guideline from the American Pain Society, the American Society of Regional Anesthesia and Pain Medicine, and the American Society of Anesthesiologists’ Committee on Regional Anesthesia, Executive Committee, and Administrative Council. J Pain. 2016;17(2):131-7. Article
Colorado Division of Workers Compensation 2014 Low Back Pain Medical Treatment Guidelines
Colorado Division of Workers Compensation 2014 Cervical Spine Injury Medical Treatment Guidelines
Kahan M, Wilson L, Mailis-Gagnon A, et al. Canadian guideline for safe and effective use of opioids for chronic noncancer pain: clinical summary for family physicians. Part 2: special populations. Can Fam Physician. 2011;57(11):1269-76, e419-28. Article
Manchikanti L, Abdi S, Atluri S, et al. American Society of Interventional Pain Physicians (ASIPP) guidelines for responsible opioid prescribing in chronic non-cancer pain: Part 2 – guidance. Pain Physician. 2012;15(3 Suppl):S67-116. Article
National Guideline Center 2016 Major Trauma: Assessment and Initial Management
National Guideline Center 2016 Spinal Injury: Assessment and Initial Management
National Guideline Center 2016 Fractures (Non-Complex): Assessment and Management
Ohio opioid prescribing guidelines. 2013
Trescot AM, Helm S, Hansen H, et al. Opioids in the management of chronic non-cancer pain. Pain Physician. 2008;11:S5-S62. Article
Trescot AM, Boswell MV, Atluri SL, et al. Opioid guidelines in the management of chronic non-cancer pain. Pain Physician. 2006;9:1-40. Article
World Health Organization 2014 Community Management of Opioid Overdose
Meta – Analyses
Reviews
Gudin JA, Mogali S, Jones JD, Comer SD. Risks, management, and monitoring of combination opioid, benzodiazepines, and / or alcohol use. Postgrad Med. 2013;125(4):115-30. Article
Jones JD, Mogali S, Comer SD. Polydrug abuse: a review of opioid and benzodiazepine combination use. Drug Alcohol Depend. 2012;125(1-2):8-18. Article
Lintzeris N, Nielsen S. Benzodiazepines, methadone and buprenorphine: interactions and clinical management. Am J Addict. 2010;19(1):59-72. Abstract
Maurer PM, Bartkowski RR. Drug interactions of clinical significance with opioid analgesics. Drug Saf. 1993;8(1):30-48. Abstract
Shyer KM, Oertel BG, Geisslinger G. Drug interactions in pain therapy. Schmerz. 2015;29(6):595-603. Abstract
5.2 Animal Studies |
Shannon HE, Holtzman SG, Davis DC. Interactions between narcotic analgesics and benzodiazepine derivatives on behavior in the mouse. J Pharmacol Exp Ther. 1976;199(2):389-99. Abstract
5.3 Epidemiology of Use |
Darke S, Ross J, Teesson M, Lynskey M. Health service utilization and benzodiazepine use among heroin users: findings from the Australian Treatment Outcome Study (ATOS). Addiction. 2003;98(8):1129-35. Abstract
Gerlach LB, Olfson M, Kales HC, Maust DT. Opioids and other central nervous system-active polypharmacy in older adults in the United States. J Am Geriatr Soc. 2017 May 7. Abstract
Guimmarra MJ, Gibson SJ, Allen AR, et al. Polypharmacy and chronic pain: harm exposure is not all about the opioids. Pain Med. 2015;16(3):472-9. Abstract
Hwang CS, Kang EM, Kornegay CJ, et al. Trends in the concomitant prescribing of opioids and benzodiazepines, 2002-2014. Am J Prev Med. 2016;51(2):151-60. Abstract
Paulozzi LJ, Strickler GK, Kreiner PW, et al. Controlled substance prescribing patterns – prescription behavior surveillance system, eight states, 2013. MMWR Surveill Summ. 2015;64(9):1-14. Abstract
Paulozzi LJ, Mack KA, Hockenberry JM. Variation among states in prescribing of opioid pain relievers and benzodiazepines – United States, 2012. J Safety Res. 2014;51:125-9. Abstract
Sakshaug S, Handal M, Hjellvik V, et al. Long-term use of Z-hypnotics and co-medication with benzodiazepines and opioids. Basic Clin Pharmacol Toxicol. 2017;120(3):292-298. Abstract
Skurveit S,Furu K Bramness J, et al. Benzodiazepines predict use of opioids – a follow-up study of 17,074 men and women. Pain Med. 2010;11(6):805-14. Article
Stein MD, Kanabar M, Anderson BJ, et al. Reasons for benzodiazepine use among persons seeking opioid detoxification. J Subst Abuse Treat. 2016;68:57-61. Astract
Sun EC, Dixit A, Humphreys K et al. Association between concurrent use of prescription opioids and benzodiazepines and overdose: retrospective analysis. BMJ. 2017;356:j760. Article
Inappropriate Prescribing
Paulozzi LJ, Stickler GK, Kreiner PW, et al. Controlled substance prescribing patterns – Prescription Behavior Surveillance System, Eight States, 2013. MMWR Surveill Summ. 2015;64(9):1-14. Abstract
In Opioid Addiction Treatment: See Addiction under Subpopulations below
Predictors of Co-Prescribing
Demyttenaere K, Bonnewyn A, Bruffaerts R, et al. Clinical factors influencing the prescription of antidepressants and benzodiazepines: results from the European study of the epidemiology of mental disorders (ESEMeD). J Affect Disord. 2008;110(1-2):84-93. Abstract
5.4 Economics of Use |
US
Lavin RA, Tao XG, Yuspeh L, Bernacki EJ. Impact of the combined use of benzodiazepines and opioids on workers’ compensation claim cost. J Occup Environ Med. 2014;56(9):973-8. Abstract
5.5 Using |
Principles
Barriers to Use
Choice of Specific Agent
Abuse Deterrent
Brand v Generic
Combination with
Modalities
Other Meds
Lintzeris N, Nielsen S. Benzodiazepines, methadone and buprenorphine: interactions and clinical management. Am J Addict. 2010;19(1):59-72. Abstract
Detection of Use
Blood
Oral Fluid
Urine
DePriest AZ, Black DL, Robert TA. Immunoassay in healthcare testing applications. J Opioid Manag. 2015;11(1):13-25. Abstract
Goulay DL, Heit HA, Coplan YH, et al. Urine drug testing in clinical practice. 2015. PharmaCon Corp. Monograph
Manchikanti L, Malla Y, Wargo BW, Fellows B. Comparative evaluation of the accuracy of benzodiazepine testing in chronic pain patients utilizing immunoassay with liquid chromatography tandem mass spectrometry (LC/MS/MS) of urine drug testing. Pain Physician. 2011;14:259-70. Article
Mikel C, Pesce A, West C. 3 things to consider before relying solely on point of care tests for determining benzodiazepine use in chronic pain. Pain Physician. 2012;15(2):E154-5; author reply E155-6. Article
Moeller KE, Lee KC, Kissack JC. Urine drug screening: practical guide for clinicians. Mayo Clin Proc. 2008;83(1):66-76. Abstract
Tenore PL. Advanced urine toxicology testing. J Addict Dis. 2010;29(4):436-48. Abstract
Discontinuing Use – See Benzodiazepine Withdrawal
Dose
Dose Ceiling
Dose Equivalents
Dose Interval
Duration of Use
Initiation
Maintenance
Monitor
Tolerance
5.6 Adverse Outcomes: Overall |
See also Benzodiazepine +/- Opioid Overdose
Ciccone DS, Just N, Bandilla EB, et al. Psychological correlates of opioid use in patients with chronic nonmalignant pain: a preliminary test of the downhill spiral hypothesis. J Pain Symptom Manage. 2000;20(3):180-92. Abstract
Drake S, Swift W, Hall W, Ross M. Drug use, HIV risk-taking and psychosocial correlates of benzodiazepine use among methadone maintenance clients. Drug Alcohol Depend. 1993;34(1):67-70. Abstract
Gummier MJ, Gibson SJ, Allen AR, et al. Polypharmacy and chronic pain: harm exposure is not all about the opioids. Pain Med. 2015;16(3):472-9. Abstract
Lee SC, Klein-Schwartz W, Doyon S, Welsh C. Comparison of toxicity associated with nonmedical use of benzodiazepines with buprenorphine or methadone. Drug Alcohol Depend. 2014;138:118-23. Abstract
Lintzeris N, Mitchell TB, Bond A, et al. Interactions on mixing diazepam with methadone or buprenorphine in maintenance patients. J Clin Psychopharmacol. 2006;26(3):274-83. Abstract
Manchikanti L, Manchikanti KN, Pampati V, Cash KA. Prevalence of side effects of prolonged low or moderate dose opioid therapy with concomitant benzodiazepine and/or antidepressant therapy in chronic non-cancer pain. Pain Physician. 2009;12:259-67. Article
Roy-Byrne P, Sullivan MD, Sherbourne CD, et al. Effects of pain and prescription opioid use on outcomes in a collaborative care intervention for anxiety. Clin J Pain. 2013;29(9):800-6. Article
Hospitalization / Emergency Department
[No authors listed] Emergency department visits involving nonmedical use of selected prescription drugs – United States, 2004-2008. Centers for Disease Control and Prevention (CDC). MMWR. 2010 Jun 18;59(23):705-9. Article
Drug Abuse Warning Network. 2011
Day C. Benzodiazepines in combination with opioid pain relievers or alcohol: greater risk of more serious ED visit outcomes. CBHSQ Report. Rockville (MD): Substance Abuse and Mental Health Services Administration (US); 2013-.2014 Dec 18. Document
5.7 Adverse Outcomes: By Organ System |
Atopy
Hematologic
Cancer
Immunologic
Dermatologic
HEENT
Respiratory
Horsfall JT, Sprague JE. The pharmacology and toxicology of the ‘Holy Trinity’. Basic Clin Pharmacol Toxicol. 2017;120(2):115-119. Abstract
Cardiovascular
GI
GU
Gyn
Obstetric
Teratogenic Potential
Musculoskeletal
Endocrine
Neurologic
Psychiatric
Ciccone DS, Just N, Bandilla EB, et al. Psychological correlates of opioid use in patients with chronic nonmalignant pain: a preliminary test of the downhill spiral hypothesis. J Pain Symptom Manage. 2000;20(3):180-92. Abstract
Combined Body Systems
5.8 Adverse Outcomes: General Function |
Lintzeris N, Mitchell TB, Bond AJ, et al. Pharmacodynamics of diazepam co-administered with methadone or buprenorphine under high dose conditions in opioid dependent patients. Drug Alcohol Depend. 2007;91(2-3):187-94. Abstract
Quality of Life
Ability
Appetite
Coordination
Endurance
Energy
Enjoyment
Injury
Mood
Outlook
Sexual Function
Sleep
Social Life
Somnolence
Strength
Weight
5.9 Adverse Outcomes: Executive Function |
Acute
Acute Cognitive Effects
Acute Cognitive Effects: Memory
Acute Psychomotor Effects
Zacny JP, Paice JA, Coalson DW. Separate and combined psychopharmacological effects of alprazolam and oxycodone in healthy volunteers. Drug Alcohol Depend. 2012;124(3):274-82. Article
Acute Psychomotor Effects: Driving
Chronic
Moreno-Ramos L, Fernández-Serrano MJ, Pérez-García M, Verdejo-García A. Impulsivity in men with prescription of benzodiazepines and methadone in prison. Adicciones. 2016 Jun 14:821. Abstract
Chronic Cognitive Effects
Rapeli P, Fabritius C, Kalska H, Alho H. Do drug treatment variables predict cognitive performance in multidrug-treated opioid-dependent patients? A regression analysis study. Subst Abuse Treat Prev Policy. 2012;7:45. Article
Rapeli P, Fabritius C, Kalska H, Alho H. Memory function in opioid-dependent patients treated with methadone or buprenorphine along with benzodiazepine: longitudinal change in comparison to healthy individuals. Subst Abuse Treat Prev Policy. 2009;4:6. Article
Chronic Cognitive Effects: Memory
Chronic Psychomotor Effects
Chronic Psychomotor Effects: Driving
5.10 Adverse Outomes: Non-medical Use |
See also Benzodiazepine Non-Medical Use
Jones JD, Mogali S, Comer SD. Polydrug abuse: a review of opioid and benzodiazepine combination use. Drug Alcohol Depend. 2012;125(1-2):8-18. Article
Addiction Liability
Bleich A, Gelkopf M, Weizman T, Adelson M. Benzodiazepine abuse in a methadone maintenance treatment clinic in Israel: characteristics and a pharmacotherapeutic approach. Isr J Psychiatry Relat Sci. 2002;39(2):104-12. Abstract
Bleich A, Gelkopf M, Schmidt V, et al. Correlates of benzodiazepine abuse in methadone maintenance treatment. A 1 year prospective study in an Israeli clinic. Addiction. 1999;94(10):1533-40. Abstract
Gelkopf M, Bleich A, Hayward R, et al. Characteristics of benzodiazepine abuse in methadone maintenance treatment patients: a 1 year prospective study in an Israeli clinic. Drug Alcohol Depend. 1999;55(1-2):63-8. Abstract
Horsfall JT, Sprague JE. The pharmacology and toxicology of the ‘Holy Trinity’. Basic Clin Pharmacol Toxicol. 2017;120(2):115-119. Abstract
Zacny JP, Paice JA, Coalson DW. Separate and combined psychopharmacological effects of alprazolam and oxycodone in healthy volunteers. Drug Alcohol Depend. 2012;124(3):274-82. Article
Craving
Diversion
Gateway
Harmful Use
Liking
Overdose – See Benzodiazepines + / – Opioid OD – OD Death
Prevention of non-medical use
Risk factors for non-medical use
5.11 Benzodiazepines + Opioids in Subpopulations |
Armed Services / Veterans
Addiction
Bramness JG, Kornør H. Benzodiazepine prescription for patients in opioid maintenance treatment in Norway. Drug Alcohol Depend. 2007;90(2-3):203-9. Abstract
Brands B, Blake J, Marsh DC, et al. The impact of benzodiazepine use on methadone maintenance treatment outcomes. J Addict Dis. 2008;27(3):37-48. Abstract
Brands B, Blake J, Marsh DC, et al. The impact of benzodiazepine use on methadone maintenance treatment outcomes. J Addict Dis. 2008;27(3):37-48. Abstract
Brazens JG, Kornør H. Benzodiazepine prescription for patients in opioid maintenance treatment in Norway. Drug Alcohol Depend. 2007;90(2-3):203-9. Abstract
Chen KW, Berger CC, Forde DP, et al. Benzodiazepine use and misuse among patients in a methadone program. BMC Psych. 2011;11:90. Article
Eiroa-Orosa FJ, Haasen C, Verthein U, et al. Benzodiazepine use among patients in heroin-assisted vs. methadone maintenance treatment: findings of the German randomized controlled trial. Drug Alcohol Depend. 2010;112(3):226-33. Abstract
Laqueille X, Launay C, Dervaux A, Kanit M. Abuse of alcohol and benzodiazepine during substitution therapy in heroin addicts: a review of the literature. Encephale. 2009;35(3):220-5. Abstract
Meiler A, Mino A, Chatton A, Broers B. Benzodiazepine use in a methadone maintenance programme: patient characteristics and the physician’s dilemma. Schweiz Arch Neurol Psychiatr 2005;156:310–7. Abstract
Nielsen S, Dietze P, Lee N, et al. Concurrent buprenorphine and benzodiazepines use and self-reported opioid toxicity in opioid substitution treatment. Addiction. 2007;102(4):616-22. Abstract
Schuman-Olivier Z, Hoeppner BB, Weiss RD, et al. Benzodiazepine use during buprenorphine treatment for opioid dependence: clinical and safety outcomes. Drug Alcohol Depend. 2013;132(3):580-6. Article
Cancer
Cardiovascular Disease
Care Facilities
Cognitive Dysfunction
Rapeli P, Fabritius C, Kalska H, Alho H. Memory function in opioid-dependent patients treated with methadone or buprenorphine along with benzodiazepine: longitudinal change in comparison to healthy individuals. Subst Abuse Treat Prev Policy. 2009;4:6 Article
Criminal Justice
Elderly
End of Life
Ethnicity
African-American
Asian
Caucasian
Hispanic
Native American
Pacific Island
Health Care Providers
Hepatic Disease
HIV / AIDS
LGBT
Men
Pain
Pediatric
Neonate
Psychiatric Disease
Pulmonary Disease
Ekström MP, Bornefalk-Hermansson A, Abernethy AP, Currow DC. Safety of benzodiazepines and opioids in very severe respiratory disease: national prospective study. BMJ. 2014;348:g445. Article
Renal Disease
Sleep Disorders
Sleep Apnea
Surgical
Swallowing Disorders
Women
Perinatal
Handal M, Engeland A, Rønning M, et al. Use of prescribed opioid analgesics and co-medication with benzodiazepines in women before, during, and after pregnancy: a population-based cohort study. Eur J Clin Pharmacol. 2011;67(9):953-60. Abstract
Nursing
