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Chronic hypnotic use at 10 years—does the brand matter?

  • Pharmacoepidemiology and Prescription
  • Published:
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Abstract

Purpose

Chronic use of sedative-hypnotics is very common, although not guideline-endorsed. The incidence among new users is not well studied, and there are currently no recommendations favoring any specific agent. We quantified the risk for chronic use in first-time hypnotic users, and the association of the initial choice of hypnotic with later usage patterns.

Methods

We used the computerized database of Israel’s largest healthcare provider. All 236,597 new users of sedative-hypnotics between the years 2000–2005 were followed for 10 years. Filled prescriptions in the second, fifth, and tenth years were recorded. The association of the first hypnotic choice (benzodiazepine/Z-drug) with chronic consumption was assessed using multivariate logistic regression.

Results

Average age on first use was 63.7 (SD ± 16.4) years. 58.6% were women. Benzodiazepines were initiated in 154,929 (65.5%) of the cases. Benzodiazepine users were older and of lower socioeconomic status, compared to Z-drug users (p < 0.001). On the tenth year, 103,912 (66.8%) of new users claimed ≤ 30 DDDs of hypnotics, 3,1724 (20.4%) were long-term users (≥ 180 DDD/year), and 828 (0.5%) used excessively (≥ 720 DDD/year). Z-drugs were associated with an increased risk of long-term use on the second year [17.3% vs. 12.4%, RR = 1.40 (1.37–1.43)] as well as on the fifth [21.9% vs. 13.9%, RR = 1.58 (1.55–1.61)] and tenth year [25.1% vs. 17.7%, RR = 1.42 (1.39–1.45)], p < 0.0001. Similar results were also observed for daily and excessive use (p < 0.001).

Conclusions

One in five new users of sedative-hypnotics will become a long-term user, but only 0.5% will become excessive users. Z-drugs were associated with an increased risk of chronic use.

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References

  1. Solomon CG, Winkelman JW (2015) Insomnia disorder. N Engl J Med 373:1437–1444. https://doi.org/10.1056/NEJMcp1412740

    Article  CAS  Google Scholar 

  2. Riemann D, Baglioni C, Bassetti C, Bjorvatn B, Dolenc Groselj L, Ellis JG, Espie CA, Garcia-Borreguero D, Gjerstad M, Gonçalves M, Hertenstein E, Jansson-Fröjmark M, Jennum PJ, Leger D, Nissen C, Parrino L, Paunio T, Pevernagie D, Verbraecken J, Weeß HG, Wichniak A, Zavalko I, Arnardottir ES, Deleanu OC, Strazisar B, Zoetmulder M, Spiegelhalder K (2017) European guideline for the diagnosis and treatment of insomnia. J Sleep Res 26:675–700. https://doi.org/10.1111/jsr.12594

    Article  PubMed  Google Scholar 

  3. Qaseem A, Kansagara D, Forciea MA, Cooke M, Denberg TD, for the Clinical Guidelines Committee of the American College of Physicians (2016) Management of chronic insomnia disorder in adults: a clinical practice guideline from the American college of physicians. Ann Intern Med 165:125–133. https://doi.org/10.7326/M15-2175

    Article  PubMed  Google Scholar 

  4. Schmitz MF (2016) The ACP guidelines for treatment of chronic insomnia: the challenge of implementation. Behav Sleep Med 14:699–700. https://doi.org/10.1080/15402002.2016.1220131

    Article  PubMed  Google Scholar 

  5. Sateia MJ, Buysse DJ, Krystal AD, Neubauer DN, Heald JL (2017) 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 J Clin Sleep Med J Clin Sleep Med 1313:307–349. https://doi.org/10.5664/jcsm.6470

    Article  Google Scholar 

  6. Bertisch SM, Herzig SJ, Winkelman JW, Buettner C (2014) National use of prescription medications for insomnia: NHANES 1999-2010. Sleep 37:343–349. https://doi.org/10.5665/sleep.3410

    Article  PubMed  PubMed Central  Google Scholar 

  7. Kripke DF (2016) Hypnotic drug risks of mortality, infection, depression, and cancer: but lack of benefit. F1000Research 5:918. doi: https://doi.org/10.12688/f1000research.8729.1

    Article  Google Scholar 

  8. Kurko TAT, Saastamoinen LK, Tähkäpää S, Tuulio-Henriksson A, Taiminen T, Tiihonen J, Airaksinen MS, Hietala J (2015) Long-term use of benzodiazepines: definitions, prevalence and usage patterns – a systematic review of register-based studies. Eur Psychiatry 30:1037–1047. https://doi.org/10.1016/j.eurpsy.2015.09.003

    Article  CAS  PubMed  Google Scholar 

  9. Anthierens S, Pasteels I, Habraken H et al (2010) Barriers to nonpharmacologic treatments for stress, anxiety, and insomnia: family physicians’ attitudes toward benzodiazepine prescribing. Can Fam physician Médecin Fam Can 56:e398–e406

    Google Scholar 

  10. Sirdifield C, Anthierens S, Creupelandt H, Chipchase SY, Christiaens T, Siriwardena AN (2013) General practitioners’ experiences and perceptions of benzodiazepine prescribing: systematic review and meta-synthesis. BMC Fam Pract 14:191. https://doi.org/10.1186/1471-2296-14-191

    Article  PubMed  PubMed Central  Google Scholar 

  11. Everitt H, Mcdermott L, Leydon G et al (2014) GPs’ management strategies for patients with insomnia : 112–119. https://doi.org/10.3399/bjgp14X677176.Conclusion

  12. Campanelli CM (2013) American Geriatrics Society Updated Beers Criteria for potentially inappropriate medication use in older adults: the American Geriatrics Society 2012 Beers Criteria Update Expert Panel. J Am Geriatr Soc 60:616–631

    Google Scholar 

  13. Oecd (2015) Health at a glance 2015. OECD Publishing

  14. Matalon A, Yinnon AM, Hurwitz A (1990) Chronic use of hypnotics in a family practice--patients’ reluctance to stop treatment. Fam Pract 7:258–260

    Article  CAS  Google Scholar 

  15. Mah L, Upshur REG (2002) Long term benzodiazepine use for insomnia in patients over the age of 60: discordance of patient and physician perceptions. BMC Fam Pract 3:9

    Article  Google Scholar 

  16. van Hulten R, Teeuw B, Bakker A, Leufkens HG (2005) Initial benzodiazepine use and improved health-related quality of life. Pharm World Sci 27:41–46

    Article  Google Scholar 

  17. Soyka M (2017) Treatment of benzodiazepine dependence. N Engl J Med 376:1147–1157. https://doi.org/10.1056/NEJMra1611832

    Article  CAS  PubMed  Google Scholar 

  18. Huedo-Medina TB, Kirsch I, Middlemass J, Klonizakis M, Siriwardena AN (2012) Effectiveness of non-benzodiazepine hypnotics in treatment of adult insomnia: meta-analysis of data submitted to the Food and Drug Administration. BMJ 345:e8343. https://doi.org/10.1136/bmj.e8343

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Krystal AD, Walsh JK, Laska E, Caron J, Amato DA, Wessel TC, Roth T (2003) Sustained efficacy of eszopiclone over 6 months of nightly treatment: results of a randomized, double-blind, placebo-controlled study in adults with chronic insomnia. Sleep 26:793–799

    Article  Google Scholar 

  20. Roehrs TA, Randall S, Harris E et al (2011) Twelve months of nightly zolpidem does not lead to dose escalation: a prospective placebo-controlled study. Sleep 34:207–212

    Article  Google Scholar 

  21. Ancoli-Israel S, Richardson GS, Mangano RM, Jenkins L, Hall P, Jones WS (2005) Long-term use of sedative hypnotics in older patients with insomnia. Sleep Med 6:107–113. https://doi.org/10.1016/j.sleep.2004.10.015

    Article  PubMed  Google Scholar 

  22. Roth T, Walsh JK, Krystal A et al (2005) An evaluation of the efficacy and safety of eszopiclone over 12 months in patients with chronic primary insomnia. Sleep Med 6:487–495. https://doi.org/10.1016/j.sleep.2005.06.004

    Article  PubMed  Google Scholar 

  23. Randall S, Roehrs TA, Roth T (2012) Efficacy of eight months of nightly zolpidem: a prospective placebo-controlled study. Sleep 35:1551–1557. https://doi.org/10.5665/sleep.2208

    Article  PubMed  PubMed Central  Google Scholar 

  24. Krystal AD, Erman M, Zammit GK, Soubrane C, Roth T, ZOLONG Study Group (2008) Long-term efficacy and safety of zolpidem extended-release 12.5 mg, administered 3 to 7 nights per week for 24 weeks, in patients with chronic primary insomnia: a 6-month, randomized, double-blind, placebo-controlled, parallel-group, multicenter study. Sleep 31:79–90

    Article  Google Scholar 

  25. Mattila T, Stoyanova V, Elferink A, Gispen-de Wied C, de Boer A, Wohlfarth T (2011) Insomnia medication: do published studies reflect the complete picture of efficacy and safety? Eur Neuropsychopharmacol 21:500–507. https://doi.org/10.1016/j.euroneuro.2010.10.005

    Article  CAS  PubMed  Google Scholar 

  26. Wilson S, Nutt D, Alford C, Argyropoulos SV, Baldwin DS, Bateson AN, Britton TC, Crowe C, Dijk DJ, Espie CA, Gringras P, Hajak G, Idzikowski C, Krystal AD, Nash JR, Selsick H, Sharpley AL, Wade AG (2010) British Association for Psychopharmacology consensus statement on evidence-based treatment of insomnia, parasomnias and circadian rhythm disorders. J Psychopharmacol 24:1577–1601. https://doi.org/10.1177/0269881110379307

    Article  CAS  PubMed  Google Scholar 

  27. Matheson E, Hainer BL (2017) Insomnia: pharmacologic therapy. Am Fam Physician 96:29–35

    PubMed  Google Scholar 

  28. Creado S, Plante DT (2016) An update on the use of sedative-hypnotic medications in psychiatric disorders. Curr Psychiatry Rep 18:78. https://doi.org/10.1007/s11920-016-0717-y

    Article  PubMed  PubMed Central  Google Scholar 

  29. Ford ES, Wheaton AG, Cunningham TJ, Giles WH, Chapman DP, Croft JB (2014) Trends in outpatient visits for insomnia, sleep apnea, and prescriptions for sleep medications among US adults: findings from the National Ambulatory Medical Care Survey 1999-2010. Sleep 37:1283–1293. https://doi.org/10.5665/sleep.3914

    Article  PubMed  PubMed Central  Google Scholar 

  30. Wilt TJ, MacDonald R, Brasure M, Olson CM, Carlyle M, Fuchs E, Khawaja IS, Diem S, Koffel E, Ouellette J, Butler M, Kane RL (2016) Pharmacologic treatment of insomnia disorder: an evidence report for a clinical practice guideline by the American college of physicians. Ann Intern Med 165:103–112. https://doi.org/10.7326/M15-1781

    Article  PubMed  Google Scholar 

  31. OECD (2012) OECD reviews of health care quality: Israel 2012. OECD Publishing

  32. The Israel Drug Registry. http://www.old.health.gov.il/units/pharmacy/trufot/index.asp?safa=e. Accessed 13 Apr 2016

  33. Ray WA (2003) Evaluating medication effects outside of clinical trials: new-user designs. Am J Epidemiol 158:915–920. https://doi.org/10.1093/aje/kwg231

    Article  PubMed  Google Scholar 

  34. WHO Collaborating Centre for Drug Statistics Methodology (2016) Guidelines for ATC classification and DDD assignment 2016. Oslo. . Oslo

  35. Zandstra SM, Furer JW, van de Lisdonk EH, van’t Hof M, Bor JHJ, van Weel C, Zitman FG (2002) Different study criteria affect the prevalence of benzodiazepine use. Soc Psychiatry Psychiatr Epidemiol 37:139–144. https://doi.org/10.1007/s001270200006

    Article  CAS  PubMed  Google Scholar 

  36. Manor O (2015) Program for quality indicators in community healthcare in Israel Report 2013-2014

  37. Cloos J-M, Bocquet V, Rolland-Portal I, Koch P, Chouinard G (2015) Hypnotics and triazolobenzodiazepines – best predictors of high-dose benzodiazepine use: results from the Luxembourg National Health Insurance Registry. Psychother Psychosom 84:273–283. https://doi.org/10.1159/000434755

    Article  PubMed  Google Scholar 

  38. Tvete IF, Bjørner T, Aursnes IA, Skomedal T (2013) A 3-year survey quantifying the risk of dose escalation of benzodiazepines and congeners to identify risk factors to aid doctors to more rationale prescribing. BMJ Open 3:e003296. https://doi.org/10.1136/bmjopen-2013-003296

    Article  PubMed  PubMed Central  Google Scholar 

  39. Greenland S, Daniel R, Pearce N (2016) Outcome modelling strategies in epidemiology: traditional methods and basic alternatives. Int J Epidemiol 45:565–575. https://doi.org/10.1093/ije/dyw040

    Article  PubMed  PubMed Central  Google Scholar 

  40. McNutt LA, Wu C, Xue X, Hafner JP (2003) Estimating the relative risk in cohort studies and clinical trials of common outcomes. Am J Epidemiol 157:940–943. https://doi.org/10.1093/aje/kwg074

    Article  PubMed  Google Scholar 

  41. Norton EC, Miller MM, Kleinman LC (2013) Computing adjusted risk ratios and risk differences in Stata. Stata J 13:492–509

    Google Scholar 

  42. Cohen R, Rabin H (2015) Membership in sick funds 2014 [Hebrew]. Jerusalem

  43. Takeshima N, Ogawa Y, Hayasaka Y, Furukawa TA (2016) Continuation and discontinuation of benzodiazepine prescriptions: a cohort study based on a large claims database in Japan. Psychiatry Res 237:201–207. https://doi.org/10.1016/j.psychres.2016.01.040

    Article  PubMed  Google Scholar 

  44. Willems IAT, Gorgels WJMJ, Oude Voshaar RC, Mulder J, Lucassen PLBJ (2013) Tolerance to benzodiazepines among long-term users in primary care. Fam Pract 30:404–410. https://doi.org/10.1093/fampra/cmt010

    Article  PubMed  Google Scholar 

  45. Soumerai SB, Simoni-Wastila L, Singer C, Mah C, Gao X, Salzman C, Ross-Degnan D (2003) Lack of relationship between long-term use of benzodiazepines and escalation to high dosages. Psychiatr Serv 54:1006–1011. https://doi.org/10.1176/appi.ps.54.7.1006

    Article  PubMed  Google Scholar 

  46. Gray SL, Eggen AE, Blough D et al (2003) Benzodiazepine use in older adults enrolled in a health maintenance organization. Am J Geriatr Psychiatry 11:568–576. https://doi.org/10.1176/appi.ajgp.11.5.568

    Article  PubMed  Google Scholar 

  47. Mandrioli R, Mercolini L, Raggi M (2008) Benzodiazepine metabolism: an analytical perspective. Curr Drug Metab 9:827–844. https://doi.org/10.2174/138920008786049258

    Article  CAS  PubMed  Google Scholar 

  48. Schutte-Rodin S, Broch L, Buysse D, Dorsey C, Sateia M (2008) Clinical guideline for the evaluation and management of chronic insomnia in adults. J Clin Sleep Med 4:487–504

    PubMed  PubMed Central  Google Scholar 

  49. Salzman C (1991) The APA Task Force report on benzodiazepine dependence, toxicity, and abuse. Am J Psychiatry 148:151–152. https://doi.org/10.1176/ajp.148.2.151

    Article  CAS  PubMed  Google Scholar 

  50. de las Cuevas C, Sanz E, de la Fuente J (2003) Benzodiazepines: more “behavioural” addiction than dependence. Psychopharmacology 167:297–303. https://doi.org/10.1007/s00213-002-1376-8

    Article  CAS  PubMed  Google Scholar 

  51. Kjosavik SR, Ruths S, Hunskaar S (2012) Use of addictive anxiolytics and hypnotics in a national cohort of incident users in Norway. Eur J Clin Pharmacol 68:311–319. https://doi.org/10.1007/s00228-011-1124-2

    Article  CAS  PubMed  Google Scholar 

  52. Yen CF, Ko CH, Chang YP, Yu CY, Huang MF, Yeh YC, Lin JJ, Chen CS (2015) Dependence, misuse, and beliefs regarding use of hypnotics by elderly psychiatric patients taking zolpidem, estazolam, or flunitrazepam. Asia Pac Psychiatry 7:298–305. https://doi.org/10.1111/appy.12147

    Article  PubMed  Google Scholar 

  53. Fang SY, Chen CY, Chang IS, Wu ECH, Chang CM, Lin KM (2009) Predictors of the incidence and discontinuation of long-term use of benzodiazepines: a population-based study. Drug Alcohol Depend 104:140–146. https://doi.org/10.1016/j.drugalcdep.2009.04.017

    Article  CAS  PubMed  Google Scholar 

  54. Ayalon L, Gross R, Yaari A, Feldhamer E, Balicer RD, Goldfracht M (2013) Patients’ and physicians’ characteristics associated with the purchase of benzodiazepines by older primary care patients in Israel. Admin Pol Ment Health 40:117–123. https://doi.org/10.1007/s10488-011-0381-9

    Article  Google Scholar 

  55. Taipale H, Koponen M, Tanskanen A et al (2015) Long-term use of benzodiazepines and related drugs among community-dwelling individuals with and without Alzheimer’s disease. Int Clin Psychopharmacol 30:202–208. https://doi.org/10.1097/YIC.0000000000000080

    Article  PubMed  Google Scholar 

  56. Haukka J, Suvisaari J, Tuulio-Henriksson A, Lönnqvist J (2007) High concordance between self-reported medication and official prescription database information. Eur J Clin Pharmacol 63:1069–1074. https://doi.org/10.1007/s00228-007-0349-6

    Article  PubMed  Google Scholar 

  57. Lacasse A, Ware MA, Bourgault P et al (2015) Accuracy of self-reported prescribed analgesic medication use. Clin J Pain 32:1–102. https://doi.org/10.1097/AJP.0000000000000248

    Article  Google Scholar 

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Authors and Affiliations

  1. Department of Family Medicine, Rabin Medical Center, Clalit Health Services, Petah Tikva, Israel

    Yochai Schonmann & Ronen Bareket

  2. Department of Quality Measurements and Research, Chief Physician’s Office, Clalit Health Services, Tel Aviv, Israel

    Yochai Schonmann, Ronen Bareket, Doron Comaneshter & Arnon D. Cohen

  3. Department of Family Medicine, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

    Yochai Schonmann, Ronen Bareket & Shlomo Vinker

  4. Division of Anesthesiology, Pain, and Intensive Care, Tel Aviv Medical Center, Tel Aviv University Sackler School of Medicine, Tel Aviv, Israel

    Or Goren

  5. Department of Public Health, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beersheba, Israel

    Or Goren

  6. Siaal Research Center for Family Medicine and Primary Care, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beersheba, Israel

    Arnon D. Cohen

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  1. Yochai Schonmann
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Correspondence to Yochai Schonmann.

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Schonmann, Y., Goren, O., Bareket, R. et al. Chronic hypnotic use at 10 years—does the brand matter?. Eur J Clin Pharmacol 74, 1623–1631 (2018). https://doi.org/10.1007/s00228-018-2531-4

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  • DOI: https://doi.org/10.1007/s00228-018-2531-4

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