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Highlights & Basics
- Benzodiazepines (BZDs) are the most commonly prescribed drugs for anxiety, sedation, and sleep. Overdose can be intentional in suicidal patients; accidental in combination with other central nervous system (CNS) depressants, such as alcohol and opioids, and in older people; and occasionally by error. Older people, who commonly have diminished drug clearance and polypharmacy, are at especially high risk of overdose.
- The key feature is excessive sedation with unremarkable vital signs and anterograde amnesia. Larger doses can cause coma and respiratory depression.
- Treatment of overdose is by symptom management, not by quantitative assay. Acute management consists of maintaining airway, respiration, and hemodynamic support while excluding other diagnoses. Assisted ventilation may be necessary.
- Death is uncommon. Most deaths from BZD overdose are from respiratory depression as a result of mixed overdoses with BZD and other respiratory depressants, particularly alcohol and opioids.
- The BZD antagonist flumazenil can be effective in select patients with respiratory depression or respiratory arrest caused by pure BZD poisoning who do not have contraindications; however, the risks of flumazenil often outweigh the benefits and its use is inappropriate for most patients presenting to the emergency department with BZD toxicity.
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Citations
Lavonas EJ, Akpunonu PD, Arens AM, et al. 2023 American Heart Association focused update on the management of patients with cardiac arrest or life-threatening toxicity due to poisoning: an update to the American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation. 2023 Oct 17;148(16):e149-84.[Abstract][Full Text]
1. Lavonas EJ, Akpunonu PD, Arens AM, et al. 2023 American Heart Association focused update on the management of patients with cardiac arrest or life-threatening toxicity due to poisoning: an update to the American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation. 2023 Oct 17;148(16):e149-84.[Abstract][Full Text]
2. Gahlinger PM. Club drugs: MDMA, gamma-hydroxybutyrate (GHB), rohypnol, and ketamine. Am Fam Physician. 2004 Jun 1;69(11):2619-27.[Abstract]
3. Gleason PP, Schulz R, Smith NL, et al. Correlates and prevalence of benzodiazepine use in community-dwelling elderly. J Gen Intern Med. 1998 Apr;13(4):243-50.[Abstract][Full Text]
4. Valenstein M, Khanujua Taylor K, Austin K, et al. Benzodiazepine use among depressed patients treated in mental health settings. Am J Psychiatry. 2004 Apr;161(4):654-61.[Abstract][Full Text]
5. Guina J, Rossetter SR, DeRhodes BJ, et al. Benzodiazepines for PTSD: a systematic review and meta-analysis. J Psychiatr Pract. 2015 Jul;21(14):281-303.[Abstract]
6. Brunoni AR, Nunes MA, Figueiredo R, et al. Patterns of benzodiazepine and antidepressant use among middle-aged adults: the Brazilian longitudinal study of adult health (ELSA-Brasil). J Affect Disord. 2013 Oct;151(1):71-7.[Abstract]
7. Préville M, Vasiliadis HM, Bossé C, et al. Pattern of psychotropic drug use among older adults having a depression or an anxiety disorder: results from the longitudinal ESA study. Can J Psychiatry. 2011 Jun;56(6):348-57.[Abstract][Full Text]
8. Saarelainen L, Tolppanen AM, Koponen M, et al. Risk of hip fracture in benzodiazepine users with and without Alzheimer disease. J Am Med Dir Assoc. 2017 Jan;18(1):87;e15-87;e21.[Abstract]
9. Taipale H, Koponen M, Tanskanen A, et al. Use of benzodiazepines and related drugs is associated with a risk of stroke among persons with Alzheimer's disease. Int Clin Psychopharmacol. 2017 May;32(3):135-41.[Abstract]
10. Huang WS, Muo CH, Chang SN, et al. Benzodiazepine use and risk of stroke: a retrospective population-based cohort study. Psychiatry Clin Neurosci. 2014 Apr;68(4):255-62.[Abstract]
11. Buckley NA, Dawson AH, Whyte IM, et al. Relative toxicity of benzodiazepines in overdose. BMJ. 1995 Jan 28;310(6974):219-21.[Abstract][Full Text]
12. Warner M, Trinidad JP, Bastian BA, et al. Drugs most frequently involved in drug overdose deaths: United States, 2010-2014. Natl Vital Stat Rep. 2016 Dec;65(10):1-15.[Abstract][Full Text]
13. Bachhuber MA, Hennessy S, Cunningham CO, et al. Increasing benzodiazepine prescriptions and overdose mortality in the United States, 1996-2013. Am J Public Health. 2016 Apr;106(4):686-8.[Abstract][Full Text]
14. National Institutes of Health, National Institute on Drug Abuse, and U.S. Department of Health and Human Services. Drug overdose death rates. Aug 2024 [internet publication].[Full Text]
15. Okamoto R, Itoh Y, Murata Y, et al. Reduction of group II metabotropic glutamate receptors during development of benzodiazepine dependence. Pharmacology. 2013;91(3-4):145-52.[Abstract]
16. Backmund M, Meyer K, Henkel C, et al. Co-consumption of benzodiazepines in heroin users, methadone-substituted and codeine-substituted patients. J Addict Dis. 2005;24(4):17-29.[Abstract]
17. Man LH, Best D, Gossop M, et al. Relationship between prescribing and risk of opiate overdose among drug users in and out of maintenance treatment. Eur Addict Res. 2004;10(1):35-40.[Abstract]
18. Gahlinger PM. Illegal drugs: a complete guide to their history, chemistry, use and abuse. New York, NY: Penguin (Plume); 2004.
19. Willems IA, Gorgels WJ, Oude Voshaar RC, et al. Tolerance to benzodiazepines among long-term users in primary care. Fam Pract. 2013 Aug;30(4):404-10.[Abstract]
20. McCabe SE, West BT. Medical and nonmedical use of prescription benzodiazepine anxiolytics among US high school seniors. Addict Behav. 2014 May;39(5):959-64.[Abstract]
21. Janhsen K, Roser P, Hoffmann K. The problems of long-term treatment with benzodiazepines and related substances. Dtsch Arztebl Int. 2015 Jan 5;112(1-2):1-7.[Abstract][Full Text]
22. Olfson M, King M, Schoenbaum M. Benzodiazepine use in the United States. JAMA Psychiatry. 2015 Feb;72(2):136-42.[Abstract]
23. Everitt H, McDermott L, Leydon G, et al. GPs' management strategies for patients with insomnia: a survey and qualitative interview study. Br J Gen Pract. 2014 Feb;64(619):e112-9.[Abstract][Full Text]
24. Lugoboni F, Mirijello A, Faccini M, et al. Quality of life in a cohort of high-dose benzodiazepine dependent patients. Drug Alcohol Depend. 2014 Sep 1;142:105-9.[Abstract]
25. Harnod T, Lin CL, Sung FC, et al. An association between benzodiazepine use and occurrence of benign brain tumors. J Neurol Sci. 2014 Jan 15;336(1-2):8-12.[Abstract][Full Text]
26. Vozoris NT, Fischer HD, Wang X, et al. Benzodiazepine use among older adults with chronic obstructive pulmonary disease: a population-based cohort study. Drugs Aging. 2013 Mar;30(3):183-92.[Abstract]
27. Billioti de Gage S, Moride Y, Ducruet T, et al. Benzodiazepine use and risk of Alzheimer's disease: case-control study. BMJ. 2014 Sep 9;349:g5205.[Abstract][Full Text]
28. Konopka A, Pełka-Wysiecka J, Grzywacz A, et al. Psychosocial characteristics of benzodiazepine addicts compared to not addicted benzodiazepine users. Prog Neuropsychopharmacol Biol Psychiatry. 2013 Jan 10;40:229-35.[Abstract]
29. Centers for Disease Control and Prevention. Stop overdose. Feb 2024 [internet publication].[Full Text]
30. Wu AH, McKay C, Broussard LA, et al. National Academy of Clinical Biochemistry laboratory medicine practice guidelines: recommendations for the use of laboratory tests to support poisoned patients who present to the emergency department. Clin Chem. 2003 Mar;49(3):357-79.[Abstract]
31. Velluti R, Pedemonte M. Differential effects of benzodiazepines on cochlear and auditory nerve responses. Electroencephalogr Clin Neurophysiol. 1986 Dec;64(6):556-62.[Abstract]
32. US Department of Veterans Affairs. VA/DoD clinical practice guidelines: assessment and management of patients at risk of suicide. 2024 [internet publication].[Full Text]
33. Bezchlibnyk-Butler JZ, Jeffries JJ. Clinical handbook of psychotropic drugs, 16th ed. Toronto, Canada: Hogrefe & Huber Publishing; 2006.
34. Haverkos GP, DiSalvo RP, Imhoff TE. Fatal seizures after flumazenil administration in a patient with mixed overdose. Ann Pharmacother. 1994 Dec;28(12):1347-9.[Abstract]
35. Spivey WH. Flumazenil and seizures: analysis of 43 cases. Clin Ther. 1992 Mar-Apr;14(2):292-305.[Abstract]
36. Kyong YY, Park JT, Choi KH. Serial monitoring of sedation scores in benzodiazepine overdose. Am J Emerg Med. 2014 Nov;32(11):1438;e5-6.[Abstract]
37. Chyka PA, Seger D, Krenzelok EP, et al. Position paper: single-dose activated charcoal. Clin Toxicol (Phila). 2005;43(2):61-87.[Abstract]
38. Pottie K, Thompson W, Davies S, et al. Deprescribing benzodiazepine receptor agonists: evidence-based clinical practice guideline. Can Fam Physician. 2018 May;64(5):339-51.[Abstract][Full Text]
39. National Institute for Health and Care Excellence. Self-harm: assessment, management and preventing recurrence. Sep 2022 [internet publication].[Full Text]
40. Darker CD, Sweeney BP, Barry JM, et al. Psychosocial interventions for benzodiazepine harmful use, abuse or dependence. Cochrane Database Syst Rev. 2015;(5):CD009652.[Abstract][Full Text]
