NOVEL MEASURES OF BENZODIAZEPINE & Z-DRUG UTILISATION TRENDS IN A CANADIAN PROVINCIAL ADULT POPULATION (2001-2016 )
Main Article Content
Keywords
Benzodiazepines, Z-Drugs, Drug Utilization, Population Use, Diazepam Milligram Equivalence, Defined Daily Dose
Abstract
Purpose
(1) To evaluate trends for benzodiazepines (BZD) and Z-Drugs over 15-years in a general Canadian adult population measured by: (a) consumption (b) pharmacologic exposure (c) dose intensity, and (d) prevalence of use. (2) To demonstrate the utility of Diazepam Milligram Equivalents (DME) based measurements when used in conjunction with traditional standard measurements of drug utilization.
Methods
Administrative data covering all prescriptions from April 2001-March 2016 for BZD and Z-Drugs for patients ?18 years was used. Consumption was calculated as DDD/1000-person days. Dose intensity (DI) was determined by conversion of individual daily doses to DME. Pharmacologic exposure (PE) was calculated as DME-DDD/1000 person days. Prevalence was determined as the proportion of the adult population with receipt of ?1 prescription in a given year. Changes were assessed using either Poisson or simple linear regression at an alpha of 0.05.
Results
Z-Drug usage (~99% zopiclone) statistically increased on every measure over the course of the study period; consumption (8.2 to 28.6 DDD/1000-person days), PE (4.1 to 14.3 DME-DDD/1000-person days), DI (5.0 to 5.43 DME/day) and prevalence (2.0% to 4.8%). For BZD the only statistically significant changes were in DI (17.1 to 20.1 DME/day) and prevalence (9.3% to 8.1%). Consumption and PE gradually increased from 2001 to 2011 for BZD before declining thus producing a non-significant trend for BZD.
Conclusion
(1) Z-Drug usage increased markedly from 2001 to 2016 whereas BZD use only increased in terms of DI. (2) DME-based measurements enable further interpretation of BZD utilization compared to sole reliance on DDD.
(1) To evaluate trends for benzodiazepines (BZD) and Z-Drugs over 15-years in a general Canadian adult population measured by: (a) consumption (b) pharmacologic exposure (c) dose intensity, and (d) prevalence of use. (2) To demonstrate the utility of Diazepam Milligram Equivalents (DME) based measurements when used in conjunction with traditional standard measurements of drug utilization.
Methods
Administrative data covering all prescriptions from April 2001-March 2016 for BZD and Z-Drugs for patients ?18 years was used. Consumption was calculated as DDD/1000-person days. Dose intensity (DI) was determined by conversion of individual daily doses to DME. Pharmacologic exposure (PE) was calculated as DME-DDD/1000 person days. Prevalence was determined as the proportion of the adult population with receipt of ?1 prescription in a given year. Changes were assessed using either Poisson or simple linear regression at an alpha of 0.05.
Results
Z-Drug usage (~99% zopiclone) statistically increased on every measure over the course of the study period; consumption (8.2 to 28.6 DDD/1000-person days), PE (4.1 to 14.3 DME-DDD/1000-person days), DI (5.0 to 5.43 DME/day) and prevalence (2.0% to 4.8%). For BZD the only statistically significant changes were in DI (17.1 to 20.1 DME/day) and prevalence (9.3% to 8.1%). Consumption and PE gradually increased from 2001 to 2011 for BZD before declining thus producing a non-significant trend for BZD.
Conclusion
(1) Z-Drug usage increased markedly from 2001 to 2016 whereas BZD use only increased in terms of DI. (2) DME-based measurements enable further interpretation of BZD utilization compared to sole reliance on DDD.
References
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2. Lader M. Benzodiazepine harm: How can it be reduced? Br J Clin Pharmacol 2014;77(2):295–301. doi:10.1111/j.1365-2125.2012.04418.x.
3. Khong TP, De Vries F, Goldenberg JSB, et al. Potential impact of benzodiazepine use on the rate of hip fractures in five large European countries and the United States. Calcif Tissue Int 2012;91(1):24–31. doi:10.1007/s00223-012-9603-8.
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5. Lingford-Hughes A, Welch S, Peters L, Nutt D. BAP updated guidelines: evidence-based guidelines for the pharmacological management of substance abuse, harmful use, addiction and comorbidity: recommendations from BAP. J Psychopharmacol 2012;26(7):899–52. doi:10.1177/0269881112444324.
6. Bandelow B, Zohar J, Hollander E, Kasper S, Moller H-J. World Federation of Societies of Biological Psychiatry (WfSBP) Guidelines for the Pharmacological Treatment of Anxiety, Obsessive-Compulsive and Psttraumatic Stress Disorders. World J Biol Psychiatry 2008;9(4):248–312. doi:10.1080/15622970802465807.
7. Sateia MJ, Buysse D, Krystal AD, Neubauer DN, Heald JL. Clinical Practice Guideline for the Pharmacologic Treatment of Chronic Insomnia in Adults: An American Academy of Sleep Medicine Clinical Practice Guideline. J Clin Sleep Med JCSM Off Publ Am Acad Sleep Med. December 2016.
8. Qaseem A, Kansagara D, Forciea MA, et al. Management of chronic insomnia disorder in adults: A clinical practice guideline from the American college of physicians. Ann Intern Med 2016;165(2):125–33. doi:10.7326/M15-2175.
9. Katzman et al. Canadian clinical practice guidelines for the management of anxiety, posttraumatic stress and obsessive-compulsive disorders. BMC Psychiatry. 2014;14(Suppl 1):1–83. doi:10.1186/1471-244X-14-S1-S1.
10. Baldwin DS, Anderson IM, Nutt DJ, et al. Evidence-based pharmacological treatment of anxiety disorders, post-traumatic stress disorder and obsessive-compulsive disorder: a revision of the 2005 guidelines from the British Association for Psychopharmacology. J Psychopharmacol 2014;28(5):403–39. doi:10.1177/0269881114525674.
11. American Geriatrics Society Expert Panel. American Geriatrics Society 2015 updated beers criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc 2015;63(11):2227–46. doi:10.1111/jgs.13702.
12. Ickowicz S, Hayashi K, Dong H, et al. Benzodiazepine use as an independent risk factor for HIV infection in a Canadian setting. Drug Alcohol Depend 2015;155:190–94. doi:10.1016/j.drugalcdep.2015.07.017.
13. Joya FL, Kripke DF, Loving RT, Dawson A, Kline LE. Meta-analyses of hypnotics and infections: Eszopiclone, ramelteon, zaleplon, and zolpidem. J Clin Sleep Med 2009;5(4):377–83.
14. Zhong G, Wang Y, Zhang Y, Zhao Y. Association between benzodiazepine use and dementia: A meta-analysis. PLoS One 2015;10(5):1–16. doi:10.1371/journal.pone.0127836.
15. Liaw G-W, Hung D-Z, Chen W-K, Lin C-L, Lin I-C, Kao C-H. Relationship between acute benzodiazepine poisoning and acute pancreatitis risk. Medicine (Baltimore) 2015;94(52):e2376. doi:10.1097/MD.0000000000002376.
16. Vozoris NT, Wang X, Fischer HD, et al. Benzodiazepine drug use and adverse respiratory outcomes among older adults with COPD. Eur Respir J 2014;44:332–40. doi:10.1183/13993003.01967-2015.
17. Brandt J, Leong C. Benzodiazepines and Z-Drugs: An updated review of major adverse outcomes reported on in epidemiologic research. Drugs R D 2017;17(4):493–507. doi:10.1007/s40268-017-0207-7.
18. Jann M, Kennedy WK, Lopez G. Benzodiazepines: a major component in unintentional prescription drug overdoses with opioid analgesics. J Pharm Pract 2014;27(1):5–16. doi:10.1177/0897190013515001.
19. Hwang CS, Kang EM, Kornegay CJ, Staffa JA, Jones CM, McAninch JK. Trends in the concomitant prescribing of opioids and benzodiazepines, 2002?2014. Am J Prev Med 2016;51(2):1–10. doi:10.1016/j.amepre.2016.02.014.
20. Olfson M, King M, Schoenbaum M. Benzodiazepine use in the United States. JAMA Psychiatr 2015;72(2):136–42. doi:10.1001/jamapsychiatry.2014.1763.
21. Sanyal C, Asbridge M, Kisely S, Sketris I, Andreou P. The utilization of antidepressants and benzodiazepines among people with major depression in Canada. Can J Psychiatr 2011;56(11):667–76. doi:10.1177/070674371105601105.
22. Berman E, Eyal S, Marom E. Trends in utilization of benzodiazepine and Z-drugs in Israel. Pharmacoepidemiol Drug Saf 2017;(September):1–6. doi:10.1002/pds.4338.
23. Islam MM, Conigrave KM, Day CA, Nguyen Y, Haber PS. Twenty-year trends in benzodiazepine dispensing in the Australian population. Intern Med J 2014;44(1):57–64. doi:10.1111/imj.12315.
24. Murphy KD, Sahm LJ, McCarthy S, Byrne S. Benzodiazepine prescribing guideline adherence and misuse potential in Irish minors. Int J Clin Pharm 2015;37(5):749–52. doi:10.1007/s11096-015-0138-8.
25. Tjagvad C, Clausen T, Handal M, Skurtveit S. Benzodiazepine prescription for patients in treatment for drug use disorders: a nationwide cohort study in Denmark, 2000-2010. BMC Psychiatr 2016;16:168. doi:10.1186/s12888-016-0881-y.
26. Alessi-Severini S, Bolton JM, Enns MW, et al. Use of benzodiazepines and related drugs in Manitoba: a population-based study. C Open 2014;2(4):E208-16. doi:10.9778/cmajo.20130076.
27. Univeristy of Manitoba. Manitoba Centre for Health Policy. Departmental Webpage. http://umanitoba.ca/faculties/health_sciences/medicine/units/chs/departmental_units/mchp/; 2017. Accessed November 6, 2017.
28. Kozyrskyj AL, Mustard CA. Validation of an electronic, population-based prescription database. Ann Pharmacother. 1998;32(11):1152–57. doi:10.1345/aph.18117.
29. Manitoba Centre for Health Policy. Population Estimates and Comparison of Data Sources. Concept Dictionary. http://mchp-appserv.cpe.umanitoba.ca/viewConcept.php?conceptID=1203; 2009. Accessed April 30, 2018.
30. WHO Collaborating Centre for Drug Statistics Methodology & Norweigan Institute of Public Health. Guidelines for ATC Classification and DDD Assignment - 2017; 2017.
31. Ashton H. The diagnosis and management of benzodiazepine dependence. Curr Opin Psychiatr 2005;18(3):249–55. doi:10.1097/01.yco.0000165594.60434.84.
32. Ashton H. benzo.org.uk?: Benzodiazepine Equivalence Table. http://www.benzo.org.uk/bzequiv.htm. Published 2007. Accessed February 3, 2017.
33. Brandt J, Alkkabanni W, Alessi-severini S, Leong C. Translating benzodiazepine utilization data into meaningful population exposure?: integration of two metrics for improved reporting. Clin Drug Investig 2018. doi:10.1007/s40261-018-0648-y.
34. Alessi-Severini S, Bolton JM, Enns MW. Sustained Use of benzodiazepines and escalation to high doses in a Canadian Population Psychiatr Serv 2016;67(9):1012–18. doi:10.1176/appi.ps.201500380.
35. Shader RI, Greenblatt DJ. Can you provide a table of equivalences for benzodiazepines and other marketed benzodiazepine receptor agonists? J Clin Psychopharmacol 1997;17(4):331.
36. Chateau D, Enns M, Ekuma O, et al. Evaluation of the Manitoba IMPRxOVE Program. Winnipeg, MB; 2015. http://mchp-appserv.cpe.umanitoba.ca/concept//ImproveRx_report_website.pdf.
37. Moore N, Pariente A, Bégaud B. Why are benzodiazepines not yet controlled substances? JAMA Psychiatr 2015;72(2):110–111. doi:10.1001/jamapsychiatry.2014.2190.
38. El-Guebaly N, Sareen J, Stein MB. Are there guidelines for the responsible prescription of benzodiazepines? Can J Psychiatr 2010;55(11):709–14.
39. Lembke A, Papac J, Humphreys K. Our other prescription drug problem. N Engl J Med 2018;378(8):693–94. doi:10.1056/NEJMp1715050.
40. 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. doi:10.1007/s40261-016-0397-8.
41. Canadian Centre on Substance Abuse. Prescription Sedatives (Canadian Drug Summary); 2015.
42. International Narcotics Control Board (INCB). Psychotropic Substances - Statistics for 2016. New York, NY: United Nations; 2018. https://www.incb.org/documents/Psychotropics/technical-publications/2017/Technical_Publication_2017_English_04042018.pdf.
43. Kurko TAT, Saastamoinen LK, Tahkapaa S, et al. Long-term use of benzodiazepines: Definitions, prevalence and usage patterns - A systematic review of register-based studies. Eur Psychiatr 2015;30(8):1037–47. doi:10.1016/j.eurpsy.2015.09.003.
44. Hausken AM, Furu K, Skurtveit S, Engeland A, Bramness JG. Starting insomnia treatment: The use of benzodiazepines versus z-hypnotics. A prescription database study of predictors. Eur J Clin Pharmacol 2009;65(3):295–301. doi:10.1007/s00228-008-0565-8.
45. Esposito E, Barbui C, Patten SB. Patterns of benzodiazepine use in a Canadian population sample. Epidemiol Psychiatr Soc 2009;18(3):248–54.
46. Lader M. Benzodiazepines revisited-will we ever learn? Addiction. 2011;106(12):2086–9. doi:10.1111/j.1360-0443.2011.03563.x.
47. Kurko T, Saastamoinen LK, Tuulio-Henriksson A, et al. Trends in the long-term use of benzodiazepine anxiolytics and hypnotics: A national register study for 2006 to 2014. Pharmacoepidemiol Drug Saf 2018;(October 2017):3–6. doi:10.1002/pds.4551.
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Jan 22, 2019
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Brandt, J., Alessi-Severini , S., Singer, A., & Leong, C. (2019). NOVEL MEASURES OF BENZODIAZEPINE & Z-DRUG UTILISATION TRENDS IN A CANADIAN PROVINCIAL ADULT POPULATION (2001-2016 ). Journal of Population Therapeutics and Clinical Pharmacology, 26(1), e22-e38. https://doi.org/10.22374/1710-6222.26.1.3
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