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drug adverse effects of benzodiazepines

Adverse effects: 1) cognitive impairment in the elderly - confusion, especially in the elderly - amnesia, aggression, delirium - impairment in inferring anger from facial expressions, posture or prosody [14] - use of benzodiazepines in the elderly is associated with increased risk of dementia [6]; RR-1.7 for >180 days use - use of benzodiazepines among older adults is associated with a 50% increased risk for developing Alzheimer disease [7] - benzodiazepine use is not associated with increased risk for dementia or Alzheimer's disease [8,15] - although both benzodiazepines & anxiety disorders increase risk of dementia in the elderly, benzodiazepine use in elderly with anxiety disorder does not increase risk of dementia [18] 2) urinary incontinence 3) increased risk falls & of hip fracture [1] 4) increased risk of community-acquired pneumonia & pneumonia-related death [4] - increased risk of pneumonia in Alzheimer's disease [11] 5) increased mortality - 2-fold increase in 8 year mortality [5] - risk may be smaller than previously reported [12] 6) use in early pregnancy is associated with increased risk for spontaneous abortion (1.4 vs 0.6%) [13] - highest risk with diazepam, temazepam, alprazolam [13] 7) withdrawal may occur within 24-48 hours after discontinuation* [2,3,16] a) moderate dose 1] agitation, anxiety 2] photophobia, phonophobia 3] paresthesias 4] muscle cramps 5] myoclonic jerks 6] tremor [3] 6] sleep disturbance 8] dizziness 9] tachycardia [3] b) high-dose 1] seizure 2] delirium c) peripheral manifestations of benzodiazepine withdrawal may be masked by beta-blockers [3] 8) benzodiazepine-induced neurological dysfunction (BIND) - associated adverse life consequences - may present during benzodiazepine use or tapering - may continue after benzodiazepine discontinuation - not all benzodiazepine users experience BIND [17] * see discontinuation of chronic benzodiazepine use

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DRUGS: benzodiazepine FORM: drug adverse effects benzodiazepine

References

  1. Wang PS et al Hazardous benzodiazepine regimens in the elderly: effects of half-life, dosage, and duration on risk of hip fracture. Am J Psychiatry 158:892 2001 PMID: 11384896
  2. The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996 pg 564
  3. Geriatric Review Syllabus, 7th edition Parada JT et al (eds) American Geriatrics Society, 2010 - Geriatric Review Syllabus, 9th edition (GRS9) Medinal-Walpole A, Pacala JT, Porter JF (eds) American Geriatrics Society, 2016 - Geriatric Review Syllabus, 11th edition (GRS11) Harper GM, Lyons WL, Potter JF (eds) American Geriatrics Society, 2022
  4. Obiora E et al The impact of benzodiazepines on occurrence of pneumonia and mortality from pneumonia: a nested case-control and survival analysis in a population-based cohort. Thorax. 5 December 2012 PMID: 23220867 http://thorax.bmj.com/content/early/2012/11/12/thoraxjnl-2012-202374
  5. Weich S et al Effect of anxiolytic and hypnotic drug prescriptions on mortality hazards: retrospective cohort study. BMJ 2014;348:g1996 PMID: 24647164 http://www.bmj.com/content/348/bmj.g1996
  6. Billioti de Gage S, Begaud B, Bazin F, Verdoux H et al Benzodiazepine use and risk of dementia: prospective population based study. BMJ. 2012 Sep 27;345:e6231. PMID: 23045258 - Billioti de Gage S et al. Benzodiazepine use and risk of Alzheimer's disease: Case- control study. BMJ 2014 Sep 9; 349:g5205 PMID: 25208536
  7. Young K, Fairchild DG, Di Francesco L Physician's First Watch, Sept 10, 2014 David G. Fairchild, MD, MPH, Editor-in-Chief Massachusetts Medical Society http://www.jwatch.org
  8. Gray SL, Dublin S, Yu O et al Benzodiazepine use and risk of incident dementia or cognitive decline: prospective population based study. BMJ 2016;352:i90 PMID: 26837813 http://www.bmj.com/content/352/bmj.i90
  9. Lader M. Benzodiazepine harm: how can it be reduced? Br J Clin Pharmacol. 2014 Feb;77(2):295-301. Review. PMID: 22882333 Free PMC Article
  10. Paquin AM, Zimmerman K, Rudolph JL. Risk versus risk: a review of benzodiazepine reduction in older adults. Expert Opin Drug Saf. 2014 Jul;13(7):919-34. Review. PMID: 24905348
  11. Taipale H, Tolppanen AM, Koponen M et al Risk of pneumonia associated with incident benzodiazepine use among community-dwelling adults with Alzheimer disease. CMAJ April 10, 2017 vol. 189 no. 14 E519-E529 PMID: 28396328 http://www.cmaj.ca/content/189/14/E519 - Rochon PA, Vozoris N, Gill SS. The harms of benzodiazepines for patients with dementia. CMAJ April 10, 2017 189:E517-E518 PMID: 28396327 http://www.cmaj.ca/content/189/14/E517
  12. Orciari Herman A, Sofair A, Chavey WE Link Between Benzodiazepines and Mortality Called into Question Physician's First Watch, July 2017 David G. Fairchild, MD, MPH, Editor-in-Chief Massachusetts Medical Society http://www.jwatch.org - Patorno E et al Benzodiazepines and risk of all cause mortality in adults: cohort study. BMJ 2017;358:j2941 http://www.bmj.com/content/358/bmj.j2941
  13. Sheehy O, Zhao JP, Berard A et al Association Between Incident Exposure to Benzodiazepines in Early Pregnancy and Risk of Spontaneous Abortion JAMA Psychiatry. Published online May 15, 2019. PMID: 31090881 https://jamanetwork.com/journals/jamapsychiatry/article-abstract/2733517
  14. Garcez H, Fernandes C, Barbosa F et al. Effects of benzodiazepines administration on identification of facial expressions of emotion: A meta-analysis. Psychopharmacology (Berl) 2019 Nov 18 PMID: 31740993
  15. Osler M, Jorgensen MB. Associations of benzodiazepines, Z-drugs, and other anxiolytics with subsequent dementia in patients with affective disorders: A nationwide cohort and nested case-control study. Am J Psychiatry 2020 Apr 7; PMID: 32252539 https://ajp.psychiatryonline.org/doi/10.1176/appi.ajp.2019.1903031
  16. Jobert A, Laforgue E, Grall-Bronnec M et al. Benzodiazepine withdrawal in older people: what is the prevalence, what are the signs, and which patients? Eur J Clin Pharmacol. 2021;77(2):171-177 PMID: 33006626 https://link.springer.com/article/10.1007/s00228-020-03007-7
  17. Rivito AD, Foster DE, Huff C et al Long-term consequences of benzodiazepine-induced neurological dysfunction: A survey. PLOS One, 2023. Jun 29;18(6):e0285584. PMID: 37384788 PMCID: PMC10309976 Free PMC article
  18. Brieler JA, Salas J, Amick ME et al Anxiety disorders, benzodiazepine prescription, and incident dementia. J Am Geriatr Soc. 2023. Nov 71(11):3376-3389 PMID: 37503956 https://agsjournals.onlinelibrary.wiley.com/doi/abs/10.1111/jgs.18515