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Benzodiazepine Prescribing in People with Chronic Obstructive Pulmonary Disease: Clinical Considerations

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Abstract

Benzodiazepines, available clinically for almost six decades, are still one of the most widely prescribed classes of medication. The proportion of the population prescribed benzodiazepines increases with age, and harms also increase with age. The prevalence of prescribing in people > 85 years of age is as high as one in three, including in people with chronic obstructive pulmonary disease (COPD). The prevalence of COPD also increases with age. In COPD, indications cited for prescribing a benzodiazepine include anxiety, sleep disorders, or chronic breathlessness. Each of these symptoms is prevalent in the population with COPD, especially later in the course of the illness. For anxiety and insomnia, there is evidence to support short-term use, with little robust evidence to support prescribing for the symptomatic reduction of chronic breathlessness. People prescribed benzodiazepines are more likely to experience drowsiness or somnolence, exacerbations of their COPD, and respiratory tract infections. Furthermore, the longer people take benzodiazepines, the more likely they will become dependent on them. Prescribing patterns vary internationally but prescriptions of longer-acting benzodiazepines are declining in favour of shorter-acting compounds. Other evidence-based therapies that can more safely treat these problematic symptoms are available. For people already taking benzodiazepines, there are a number of interventions that have been shown to reduce the rate of prescribing. For people with COPD and not taking a benzodiazepine, but with symptoms where there is evidence of benefit, clinicians should weigh carefully the potential net benefit and prescribe at the lowest dose for the briefest time possible.

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References

  1. Tsai SC. Chronic obstructive pulmonary disease and sleep related disorders. Curr Opin Pulm Med. 2017;23(2):124–8.

    Article  PubMed  Google Scholar 

  2. Johnson MJ, Yorke J, Hansen-Flaschen J, Lansing R, Ekström M, Similowski T, et al. Towards an expert consensus to delineate a clinical syndrome of chronic breathlessness. Eur Respir J. 2017. https://doi.org/10.1183/13993003.02277-2016.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Singh D, Agusti A, Anzueto A, Barnes PJ, Bourbeau J, Celli BR, et al. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Lung Disease: the GOLD science committee report 2019. Eur Respir J. 2019. https://doi.org/10.1183/13993003.00164-2019.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Kunik ME, Roundy K, Veazey C, Souchek J, Richardson P, Wray NP, et al. Surprisingly high prevalence of anxiety and depression in chronic breathing disorders. Chest. 2005;127(4):1205–11.

    PubMed  Google Scholar 

  5. Maurer J, Rebbapragada V, Borson S, Goldstein R, Kunik ME, Yohannes AM, et al. Anxiety and depression in COPD: current understanding, unanswered questions, and research needs. Chest. 2008;134(4 Suppl):43S–56S.

    Article  PubMed  Google Scholar 

  6. Currow DC, Chang S, Reddel H, Kochovska S, Ferreira D, Johnson MJ, et al. Breathlessness, anxiety, depression and function—the BAD-F study: a cross-sectional, population prevalence study in adults. J Pain Symptom Manag. 2020;59(2):197–205.e2.

    Article  Google Scholar 

  7. Nishimura K, Izumi T, Tsukino M, Oga T. Dyspnea is a better predictor of 5-year survival than airway obstruction in patients with COPD. Chest. 2002;121(5):1434–40.

    Article  PubMed  Google Scholar 

  8. Wick JY. The history of benzodiazepines. Consult Pharm. 2013;28(9):538–48.

    Article  PubMed  Google Scholar 

  9. Longo LP, Johnson B. Addiction: part 1. Benzodiazepines—side effects, abuse risk and alternatives. Am Fam Physician. 2000;61:2121–8.

    CAS  PubMed  Google Scholar 

  10. Lader M, Kyriacou A. Withdrawing benzodiazepines in patients with anxiety disorders. Curr Psychiatry Rep. 2016;18(1):8.

    Article  PubMed  Google Scholar 

  11. Jorm AF, Grayson D, Creasey H, Waite L, Broe GA. Long-term benzodiazepine use by elderly people living in the community. Aust N Z J Public Health. 2000;24(1):7–10.

    Article  CAS  PubMed  Google Scholar 

  12. Simon GE, Ludman EJ. Outcome of new benzodiazepine prescriptions to older adults in primary care. Gen Hosp Psychiatry. 2006;28(5):374–8.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Hämmeralein A, Derendorf H, Lowenthal DT. Pharmacokinetic and pharmacodynamics changes in the elderly. Clin Pharmacokinet. 1998;35(1):49–64.

    Article  Google Scholar 

  14. Geddes DM, Rudolf M, Saunders KB. Effect of nitrazepam and flurazepam on the ventilator response to carbon dioxide. Thorax. 1976;31:548–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Lu K-M, Zhu J-PZX-M. The effect of benzodiazepines on insomnia in patients with chronic obstructive pulmonary disease: a meta-analysis of treatment efficacy and safety. Int J COPD. 2016;11:675–85.

    Article  CAS  Google Scholar 

  16. Guilleminault C. Benzodiazepines, breathing and sleep. Am J Med. 1990;88(Suppl 3A):25S–8S.

    Article  CAS  PubMed  Google Scholar 

  17. Sieghart W. Pharmacology of benzodiazepine receptors: an update. J Psychiatr Neurosci. 1994;19(1):24–9.

    CAS  Google Scholar 

  18. Obiora E, Hubbard R, Sanders RD, Myles PR. 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. 2013;68(2):163–70.

    Article  PubMed  Google Scholar 

  19. Stephens DN, King SL, Lambert JJ, Belelli D, Duka T. GABAA receptor subtype involvement in addictive behaviour. Genes Brain Behav. 2017;16(1):149–84.

    Article  CAS  PubMed  Google Scholar 

  20. Chen TR, Huang HC, Hsu JH, Ouyang WC, Lin KC. Pharmacological and psychological interventions for generalized anxiety disorder in adults: a network meta-analysis. J Psychiatr Res. 2019;118:73–83. https://doi.org/10.1016/j.jpsychires.2019.08.014.

    Article  PubMed  Google Scholar 

  21. Shinfuku M, Kishimoto T, Uchida H, Suzuki T, Mimura M, Kikuchi T. Effectiveness and safety of long-term benzodiazepine use in anxiety disorders: a systematic review and meta-analysis. Int Clin Psychopharmacol. 2019;34(5):211–21.

    Article  PubMed  Google Scholar 

  22. Slee A, Nazareth I, Bondaronek P, Liu Y, Cheng Z, Freemantle N. Pharmacological treatments for generalised anxiety disorder: a systematic review and network meta-analysis. Lancet. 2019;393(10173):768–77.

    Article  CAS  PubMed  Google Scholar 

  23. Gomez AF, Barthel AL, Hofmann SG. Comparing the efficacy of benzodiazepines and serotonergic anti-depressants for adults with generalized anxiety disorder: a meta-analytic review. Expert Opin Pharmacother. 2018;19(8):883–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Mayo-Wilson E, Dias S, Mavranezouli I, Kew K, Clark DM, Ades AE, et al. Psychological and pharmacological interventions for social anxiety disorder in adults: a systematic review and network meta-analysis. Lancet Psychiatry. 2014;1(5):368–76. https://doi.org/10.1016/S2215-0366(14)70329-3.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Williams T, Hattingh CJ, Kariuki CM, Tromp SA, van Balkom AJ, Ipser JC, et al. Pharmacotherapy for social anxiety disorder (SAnD). Cochrane Database Syst Rev. 2017. https://doi.org/10.1002/14651858.cd001206.pub3.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Bighelli I, Trespidi C, Castellazzi M, Cipriani A, Furukawa TA, Girlanda F, et al. Antidepressants and benzodiazepines for panic disorder in adults. Cochrane Database Syst Rev. 2016. https://doi.org/10.1002/14651858.cd011567.pub2.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Budhiraja R, Parthasarathy S, Budhiraja P, Habib MP, Wendel C, Quan SF. Insomnia in patients with COPD. Sleep. 2012;35(3):360–75.

    Article  Google Scholar 

  28. Winkler A, Auer C, Doering BK, Rief W. Drug treatment of primary insomnia: a meta-analysis of polysomnographic randomized controlled trials. CNS Drugs. 2014;28(9):799–816.

    Article  CAS  PubMed  Google Scholar 

  29. Buscemi N, Vandermeer B, Friesen C, Bialy L, Tubman M, Ospina M, et al. The efficacy and safety of drug treatments for chronic insomnia in adults: a meta-analysis of RCTs. J Gener Intern Med. 2007;22(9):1335–50.

    Article  Google Scholar 

  30. Simon ST, Higginson IJ, Booth S, Harding R, Weingärtner V, Bausewein C. Benzodiazepines for the relief of breathlessness in advanced malignant and non-malignant diseases in adults. Cochrane Database Syst Rev. 2016;10:CD007354.

    PubMed  Google Scholar 

  31. Peoples AR, Bushunow PW, Garland SN, Heckler CE, Roscoe JA, Peppone LL, et al. Buspirone for management of dyspnea in cancer patients receiving chemotherapy: a randomized placebo-controlled URCC CCOP study. Support Care Cancer. 2016;24(3):1339–47.

    Article  PubMed  Google Scholar 

  32. Currow DC, Ekström M, Louw S, Hill J, Fazekas B, Clark K, et al. Sertraline in symptomatic chronic breathlessness: a double blind, randomised trial. Eur Respir J. 2019;53(1).

  33. Allcroft P, Margitanovic V, Greene A, Agar MR, Clark K, Abernethy AP, et al. The role of benzodiazepines in breathlessness: a single site, open label pilot of sustained release morphine together with clonazepam. J Palliat Med. 2013;16(7):741–4.

    Article  PubMed  Google Scholar 

  34. Holbrook AM, Crowther R, Lotter A, Cheng C, King D. Meta-analysis of benzodiazepine use in the treatment of insomnia. CMAJ. 2000;162(2):225–33.

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Murphy Y, Wilson E, Goldner EM, Fischer B. Benzodiazepine use, misuse, and harm at the population level in Canada: a comprehensive narrative review of data and developments since 1995. Clin Drug Investig. 2016;36(7):519–30.

    Article  CAS  PubMed  Google Scholar 

  36. Poly TN, Islam MM, Yang HC, Li YJ. Association between benzodiazepines use and risk of hip fracture in the elderly people: a meta-analysis of observational studies. Jt Bone Spine. 2019. https://doi.org/10.1016/j.jbspin.2019.11.003(Epub 25 Nov 2019).

    Article  Google Scholar 

  37. Nowell PD, Mazumdar S, Buysse DJ, Dew MA, Reynolds CF 3rd, Kupfer DJ. Benzodiazepines and zolpidem for chronic insomnia: a meta-analysis of treatment efficacy. JAMA. 1997;278(24):2170–7.

    Article  CAS  PubMed  Google Scholar 

  38. Parsaik AK, Mascarenhas SS, Khosh-Chashm D, Hashmi A, John V, Okusaga O, et al. Mortality associated with anxiolytic and hypnotic drugs: a systematic review and meta-analysis. Aust N Z J Psychiatry. 2016;50(6):520–33.

    Article  PubMed  Google Scholar 

  39. Chung WS, Lai CY, Lin CL, Kao CH. Adverse respiratory events associated with hypnotics use in patients of chronic obstructive pulmonary disease: a population-based case-control study. Medicine (Baltimore). 2015;94(27):e1110.

    Article  Google Scholar 

  40. Lu XM, Zhu JP, Zhou XM. The effect of benzodiazepines on insomnia in patients with chronic obstructive pulmonary disease: a meta-analysis of treatment efficacy and safety. Int J Chron Obstruct Pulmon Dis. 2016;11:675–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Mason M, Cates CJ, Smith I. Effects of opioid, hypnotic and sedating medications on sleep-disordered breathing in adults with obstructive sleep apnoea. Cochrane Database Syst Rev. 2015;7:CD011090.

    Google Scholar 

  42. Rodriguez-Roisin R, Garcia-Aymerich J. Should we exercise caution with benzodiazepine use in patients with COPD? Eur Respir J. 2014;44(2):284–6.

    Article  CAS  PubMed  Google Scholar 

  43. Vozoris NT, Fischer HD, Wang X, Stephenson AL, Gershon AS, Gruneir A, et al. Benzodiazepine drug use and adverse respiratory outcomes among older adults with COPD. Eur Respir J. 2014;44(2):332–40.

    Article  CAS  PubMed  Google Scholar 

  44. 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  CAS  PubMed  PubMed Central  Google Scholar 

  45. Chen SJ, Yeh CM, Chao TF, Liu CJ, Wang KL, Chen TJ, et al. The use of benzodiazepine receptor agonists and risk of respiratory failure in patients with chronic obstructive pulmonary disease: a nationwide population-based case-control study. Sleep. 2015;38(7):1045–50.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Vozoris NT, Fischer HD, Wang X, Anderson GM, Bell CM, Gershon AS, et al. Benzodiazepine use among older adults with chronic obstructive pulmonary disease: a population-based cohort study. Drugs Aging. 2013;30:183–92.

    Article  CAS  PubMed  Google Scholar 

  47. Tu K, Mamdani MM, Hux JE, Tu J. Progressive trends in the prevalence of benzodiazepine prescribing in older people in Ontario, Canada. J Am Geriatri Soc. 2001;49(10):1341–5.

    Article  CAS  Google Scholar 

  48. Mell T, Jacob L, Fuhr I, Dick S, Rapp MA, Kostev K. Patterns of benzodiazepine prescribing by neuropsychiatrists and general practitioners for elderly patients in Germany in 2014. Int J Clin Pharmacol Ther. 2017;55(6):466–71.

    Article  PubMed  Google Scholar 

  49. NICE National Institute for Health and Care Excellence. Clinical Knowledge Summary - insomnia. https://www.nice.org.uk/insomnia. Accessed 24 Feb 2020.

  50. Ford ES, Wheaton AG. Trends in outpatient visits with benzodiazepines among US adults with and without bronchitis or chronic obstructive pulmonary disease from 1999 to 2010. COPD. 2015;12(6):649–57.

    PubMed  Google Scholar 

  51. Kaufmann CN, Spira AP, Alexander GC, Rutkow L, Mojtabai R. Trends in prescribing of sedative-hypnotic medications in the USA: 1993-2010. Pharmacoepidemiol Drug Saf. 2016;25(6):637–45.

    Article  CAS  PubMed  Google Scholar 

  52. Greenblatt DJ, Harmatz JS, Shader RI. Update on psychotropic drug prescribing in the United States 2014-2015. J Clin Psychopharmacol. 2019;38(1):1–3.

    Article  Google Scholar 

  53. Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD). 2017. http://goldcopd.org. Accessed 15 Jan 2020.

  54. National Institute for Health and Care Excellence. Chronic obstructive pulmonary disease in over 16 s: diagnosis and management. 2010. https://www.nice.org.uk/guidance/cg101/resources/chronic-obstructive-pulmonary-disease-in-over-16s-diagnosis-and-management-pdf-35109323931589. Accessed 15 Jan 2020.

  55. Parshall MB, Schwartzstein RM, Adams L, Banzett RB, Manning HL, Bourbeau J, et al. An official American Thoracic Society statement: update on the mechanisms, assessment, and management of dyspnea. Am J Respir Crit Care Med. 2012;185(4):435–52.

    Article  PubMed  PubMed Central  Google Scholar 

  56. George CF, Bayliff CD. Management of insomnia in patients with chronic obstructive pulmonary disease. Drugs. 2003;63(4):379–87.

    Article  PubMed  Google Scholar 

  57. Steens RD, Pouliot Z, Millar TW, Kryger MH, George CF. Effects of zolpidem and triazolam on sleep and respiration in mild to moderate chronic obstructive pulmonary disease. Sleep. 1993;16(4):318–26.

    Article  CAS  PubMed  Google Scholar 

  58. Kryger M, Roth T, Wang-Weigand S, Zhang J. The effects of ramelteon on respiration during sleep in subjects with moderate to severe chronic obstructive pulmonary disease. Sleep Breath. 2009;13(1):79–84.

    Article  PubMed  Google Scholar 

  59. Nunes DM, Mota RM, Machado MO, Pereira ED, Bruin VM, Bruin PF. Effect of melatonin administration on subjective sleep quality in chronic obstructive pulmonary disease. Braz J Med Biol Res. 2008;41:926–31.

    Article  CAS  PubMed  Google Scholar 

  60. Marciniuk DD, Goodridge D, Hernandez P, Rocker G, Balter M, Bailey P, et al. Managing dyspnea in patients with advanced chronic obstructive pulmonary disease: a Canadian Thoracic Society clinical practice guideline. Can Respir J. 2011;18(2):69–78.

    Article  PubMed  PubMed Central  Google Scholar 

  61. Ekstrom M, Nilsson F, Abernethy AP, Currow DC. Effects of opioids on breathlessness and exercise capacity in chronic obstructive pulmonary disease. A systematic review. Ann Am Thoracic Soc. 2015;12(7):1079–92.

    Article  Google Scholar 

  62. Ekström M, Bajwah S, Bland JM, Currow DC, Hussain J, Johnson MJ. One evidence base; three stories: do opioids relieve chronic breathlessness? Thorax. 2018;73:88–90.

    Article  PubMed  Google Scholar 

  63. Halvorsen T, Martinussen PE. Benzodiazepine us in COPD: empirical evidence from Norway. Int J COPD. 2015;10:1695–702.

    CAS  Google Scholar 

  64. Parr JM, Kavanagh DJ, Cahill L, Mitchell G, McD Young R. Effectiveness of current treatment approaches for benzodiazepine discontinuation: a meta-analysis. Addiction. 2009;104(1):13–24.

    Article  PubMed  Google Scholar 

  65. Voshaar RC, Couvée JE, van Balkom AJ, Mulder PG, Zitman FG. Strategies for discontinuing long-term benzodiazepine use: meta-analysis. Br J Psychiatry. 2006;189:213–20.

    Article  PubMed  Google Scholar 

  66. Gould RL, Coulson MC, Patel N, Highton-Williamson E, Howard RJ. Interventions for reducing benzodiazepine use in older people: meta-analysis of randomised controlled trials. Br J Psychiatry. 2014;204(2):98–107.

    Article  PubMed  Google Scholar 

  67. Mugunthan K, McGuire T, Glasziou P. Minimal interventions to decrease long-term use of benzodiazepines in primary care: a systematic review and meta-analysis. Br J Gen Pract. 2011;61(590):e573–8.

    Article  PubMed  PubMed Central  Google Scholar 

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  1. IMPACCT (Improving Palliative, Aged and Chronic Care through Clinical Research and Translation), Faculty of Health, University of Technology Sydney, PO Box 123, Ultimo, NSW, 2007, Australia

    David C. Currow & Meera R. Agar

  2. Wolfson Palliative Care Research Centre, Hull York Medical School, University of Hull, Hull, UK

    David C. Currow

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Correspondence to David C. Currow.

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David C. Currow has received intellectual property payments and consultancy fees from Mayne Pharma Pty Ltd, consultancy fees from Specialist Therapeutics Pty Ltd, and is on an Advisory Board for Helsinn Pharmaceuticals. Meera R. Agar declares no competing interests.

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Currow, D.C., Agar, M.R. Benzodiazepine Prescribing in People with Chronic Obstructive Pulmonary Disease: Clinical Considerations. Drugs Aging 37, 263–270 (2020). https://doi.org/10.1007/s40266-020-00756-z

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