Use of Benzodiazepines in Treatment of Depression and Anxiety in Patients with Chronic Obstructive Pulmonary Disease. Trends, Controversies and Alternatives
Main Article Content
Abstract
Chronic obstructive pulmonary disease (COPD) is primarily affecting the lungs but is also associated with a number of accompanying conditions known as comorbidities. Depression, anxiety and insomnia are very common among older people and especially those with COPD. Treatment of these conditions is often related to prescription of benzodiazepines, a class of drugs which is highly addictive and has adverse effects on the respiratory function. Despite of the known harms and controversial benefits, the use of benzodiazepines in the general population and in COPD patients is increasing. In this article are discussed the mechanisms of coexistence of anxiety and depression in COPD patients and the use of benzodiazepines in their treatment: trends of prescription, indications and harmful effects. The use of this group of medications is a matter of debate and suggests further use of alternative treatment, more specific personalized therapeutic approach and non-pharmacological interventions.
Keywords:
COPD, benzodiazepines, anxiety, depression, non-pharmacological treatment
Article Details
How to Cite
STRATEV, Velin K.; SØBORG, Christian.
Use of Benzodiazepines in Treatment of Depression and Anxiety in Patients with Chronic Obstructive Pulmonary Disease. Trends, Controversies and Alternatives.
Medical Research Archives, [S.l.], v. 13, n. 7, july 2025.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/6686>. Date accessed: 06 dec. 2025.
doi: https://doi.org/10.18103/mra.v13i7.6686.
Section
Review Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
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3. Stratev, Velin; Fjeldstad, Odd-Magne. Comorbidities of COPD: Mechanisms and Treatment. Update 2023. Medical Research Archives, [S.l.], v. 11, n. 6, june 2023. ISSN 2375-1924. doi: 10.18103/mra.v11i6.3949.
4. Hill K, Geist R, Goldstein RS, Lacasse Y. Anxiety and depression in end-stage COPD. Eur Respir J. 2008;31(3):667-677. doi:10.1183/09031936.00125707
5. 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;30(3):183-192. doi:10.1007/s40266-013-0056-1
6. Halvorsen T, Martinussen PE. Benzodiazepine use in COPD: empirical evidence from Norway. Int J Chron Obstruct Pulmon Dis. 2015;10:1695-1702. Published 2015 Aug 27. doi:10.2147/COPD.S83107
7. Yohannes AM, Alexopoulos GS. Depression and anxiety in patients with COPD. Eur Respir Rev. 2014;23(133):345-349. doi:10.1183/09059180.00007813
8. Tselebis A, Pachi A, Ilias I, et al. Strategies to improve anxiety and depression in patients with COPD: a mental health perspective. Neuropsychiatr Dis Treat. 2016;12:297-328. Published 2016 Feb 9. doi:10.2147/NDT.S79354
9. Hynninen KM, Breitve MH, Wiborg AB, Pallesen S, Nordhus IH. Psychological characteristics of patients with chronic obstructive pulmonary disease: a review. J Psychosom Res. 2005;59(6):429-443. doi:10.1016/j.jpsychores.2005.04.007
10. Solano JP, Gomes B, Higginson IJ. A comparison of symptom prevalence in far advanced cancer, AIDS, heart disease, chronic obstructive pulmonary disease and renal disease. J Pain Symptom Manage. 2006;31(1):58-69. doi:10.1016/j.jpainsymman.2005.06.007
11. Hanania NA, Müllerova H, Locantore NW, et al. Determinants of depression in the ECLIPSE chronic obstructive pulmonary disease cohort. Am J Respir Crit Care Med. 2011;183(5):604-611. doi:10.1164/rccm.201003-0472OC.
12. Schneider C, Jick SS, Bothner U, Meier CR. COPD and the risk of depression. Chest. 2010;137(2):341-347. doi:10.1378/chest.09-0614
13. Ishii T, Wakabayashi R, Kurosaki H, Gemma A, Kida K. Association of serotonin transporter gene variation with smoking, chronic obstructive pulmonary disease, and its depressive symptoms. J Hum Genet. 2011;56(1):41-46. doi:10.1038/jhg.2010.133
14. Norwood R. Prevalence and impact of depression in chronic obstructive pulmonary disease patients. Curr Opin Pulm Med. 2006;12(2):113-117. doi:10.1097/01.mcp.0000208450.50231.c6
15. Eagan TM, Ueland T, Wagner PD, et al. Systemic inflammatory markers in COPD: results from the Bergen COPD Cohort Study. Eur Respir J. 2010;35(3):540-548. doi:10.1183/09031936.00088209
16. Currow DC, Agar MR. Benzodiazepine Prescribing in People with Chronic Obstructive Pulmonary Disease: Clinical Considerations. Drugs Aging. 2020;37(4):263-270. doi:10.1007/s40266-020-00756-z
17. 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):163-170. doi:10.1136/thoraxjnl-2012-202374
18. 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. doi:10.1111/j.1467-842x.2000.tb00715.x
19. Simon GE, Ludman EJ. Outcome of new benzodiazepine prescriptions to older adults in primary care. Gen Hosp Psychiatry.2006;28(5):374-378. doi:10.1016/j.genhosppsych.2006.05.008
20. Murciano D, Armengaud MH, Cramer PH, et al. Acute effects of zolpidem, triazolam and flunitrazepam on arterial blood gases and control of breathing in severe COPD. Eur Respir J. 1993;6(5):625-629.
21. Cohn MA, Morris DD, Juan D. Effects of estazolam and flurazepam on cardiopulmonary function in patients with chronic obstructive pulmonary disease. Drug Saf. 1992;7(2):152-158. doi:10.2165/00002018-199207020-00006
22. Beaupré A, Soucy R, Phillips R, Bourgouin J. Respiratory center output following zopiclone or diazepam administration in patients with pulmonary disease. Respiration. 1988;54(4):235-240. doi:10.1159/000195530
23. 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;11:675-685. Published 2016 Apr 4. doi:10.2147/COPD.S98082
24. 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. doi:10.1016/j.jpsychires.2019.08.014
25. Williams T, Hattingh CJ, Kariuki CM, et al. Pharmacotherapy for social anxiety disorder (SAnD). Cochrane Database Syst Rev. 2017;10(10):CD001206. Published 2017 Oct 19. doi:10.1002/14651858.CD001206.pub3
26. Budhiraja R, Parthasarathy S, Budhiraja P, Habib MP, Wendel C, Quan SF. Insomnia in patients with COPD. Sleep. 2012;35(3):369-375. Published 2012 Mar 1. doi:10.5665/sleep.1698
27. 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. doi:10.1007/s40263-014-0198-7
28. 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(10):CD007354. Published 2016 Oct 20. doi:10.1002/14651858.CD007354.pub3
29. Allcroft P, Margitanovic V, Greene A, 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):741-744. doi:10.1089/jpm.2012.0505
30. Rosenqvist TW, Wium-Andersen MK, Wium-Andersen IK, Jørgensen MB, Osler M. Long-Term Use of Benzodiazepines and Benzodiazepine-Related Drugs: A Register-Based Danish Cohort Study on Determinants and Risk of Dose Escalation [published correction appears in Am J Psychiatry. 2024 Mar 1;181(3):254. doi: 10.1176/appi.ajp.2023007 5correction.]. Am J Psychiatry. 2024;181(3):246-254. doi:10.1176/appi.ajp.20230075
31. Tu K, Mamdani MM, Hux JE, Tu JB. Progressive trends in the prevalence of benzodiazepine prescribing in older people in Ontario, Canada. J Am Geriatr Soc. 2001;49(10):1341-1345. doi:10.1046/j.1532-5415.2001.49262.x
32. 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):649-657. doi:10.3109/15412555.2015.1007932
33. 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):637-645. doi:10.1002/pds.3951
34. 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;11:675-685. Published 2016 Apr 4. doi:10.2147/COPD.S98082
35. 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. Published 2014 Jan 30. doi:10.1136/bmj.g445
36. Chen SJ, Yeh CM, Chao TF, 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):1045-1050. Published 2015 Jul 1. doi:10.5665/sleep.4808
37. George CF, Bayliff CD. Management of insomnia in patients with chronic obstructive pulmonary disease. Drugs. 2003;63(4):379-387. doi:10.2165/00003495-200363040-00004
38. 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):318-326. doi:10.1093/sleep/16.4.318
39. 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. doi:10.1007/s11325-008-0196-4
40. 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(10):926-931. doi:10.1590/s0100-879x2008001000016
41. National Institute for Health and Clinical Excellence. CG91 Depression with a Chronic Physical Health Problem: NICE Guideline. London, UK: National Collaborating Centre for Mental Health; 2009. Available from: https://www.nice.org.uk/guidance/cg91. [accessed 2025 June 06].
42. Tselebis A, Bratis D, Pachi A, et al. Anxiety and depression in patients with chronic obstructive pulmonary disease (COPD). In: Zirimis L, Papazoglakis A, editors. Chronic Obstructive Pulmonary Disease:New Research. New York, NY: Nova Science Publishers; 2013:15–40
43. Heslop K, De Soyza A, Baker CR, Stenton C, Burns GP. Using individualised cognitive behavioural therapy as a treatment for people with COPD. Nurs Times. 2009;105(14):14-17.
44. Kunik ME, Braun U, Stanley MA, et al. One session cognitive behavioural therapy for elderly patients with chronic obstructive pulmonary disease. Psychol Med. 2001;31(4):717-723. doi:10.1017/s0033291701003890
45. Ma RC, Yin YY, Wang YQ, Liu X, Xie J. Effectiveness of cognitive behavioural therapy for chronic obstructive pulmonary disease patients: A systematic review and meta-analysis. Complement Ther Clin Pract. 2020;38:101071. doi:10.1016/j.ctcp.2019.101071
46. Zuwallack R. The nonpharmacologic treatment of chronic obstructive pulmonary disease: advances in our understanding of pulmonary rehabilitation. Proc Am Thorac Soc. 2007;4(7):549-553. doi:10.1513/pats.200701-015FM47.
47. Paz-Díaz H, Montes de Oca M, López JM, Celli BR. Pulmonary rehabilitation improves depression, anxiety, dyspnea and health status in patients with COPD. Am J Phys Med Rehabil. 2007;86(1):30-36. doi:10.1097/phm.0b013e31802b8eca
48. Jácome C, Marques A. Impact of pulmonary rehabilitation in subjects with mild COPD. Respir Care. 2014;59(10):1577-1582. doi:10.4187/respcare.03091
49. Alexopoulos GS, Sirey JA, Raue PJ, et al. Outcomes of depressed patients undergoing inpatient pulmonary rehabilitation. Am J Geriatr Psychiatry. 2006;14:466–475.
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