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Twelve-year trend in the use of zolpidem and physicians’ non-compliance with recommended duration: a Korean national health insurance database study

  • Pharmacoepidemiology and Prescription
  • Published:
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Abstract

Objectives

Abuse of zolpidem has sporadically been reported and little is known regarding nationwide patterns of zolpidem use in Korea. This study investigates the extent of zolpidem usage exceeding the recommended duration and the predictors.

Methods

We conducted a drug utilization study using the national sample cohort database of the Korea National Health Insurance Corporation between 2002 and 2013. The study subjects were patients treated with zolpidem in the outpatient setting. An episode was defined as a period of continuous zolpidem therapy. The provider-based episode allowed for a gap of up to 3 days between two consecutive prescriptions from the same institution. The person-based episode allowed for a gap of up to 3 days, regardless of institution. We calculated the proportion of zolpidem use for periods over 30 days and conducted logistic regression analyses to investigate the relevant predictors. An adjusted odds ratio (aOR) with a 95% confidence interval (CI) was estimated for each predictor.

Results

The usage of zolpidem is dramatically increased by approximately 18 times since zolpidem was authorized in the market (1181 in 2002 vs. 21,399 in 2013). The treatment duration in 8.3% of episodes exceeded 30 days out of 75,087 zolpidem users. The odds of zolpidem prescription exceeding 30 days were highest in patients aged 65 years and older (aOR = 2.13, 95% CI 1.78–2.53) and at tertiary hospitals (aOR = 2.14, 95% CI 1.68–2.72). Women were more likely than men to be treated with zolpidem for over 30 days.

Conclusion

We found dramatic increase of zolpidem use from 2002 to 2013. In 8.3% of the prescribed episodes of zolpidem, the recommended duration was exceeded. Efforts are required to reduce prescriptions that are inconsistent with the recommended guidelines for older patients, women, and in tertiary hospitals.

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References

  1. Rush CR (1998) Behavioral pharmacology of zolpidem relative to benzodiazepines: a review. Pharmacol Biochem Behav 61:253–269

    Article  CAS  PubMed  Google Scholar 

  2. Darcourt G, Pringuey D, Sallière D, Lavoisy J (1999) The safety and tolerability of zolpidem--an update. J Psychopharmacol 13:81–93. https://doi.org/10.1177/026988119901300109

    Article  CAS  PubMed  Google Scholar 

  3. Terzano MG, Rossi M, Palomba V, Smerieri A, Parrino L (2003) New drugs for insomnia: comparative tolerability of zopiclone, zolpidem and zaleplon. Drug Saf 26:261–282

    Article  CAS  PubMed  Google Scholar 

  4. Holm KJ, Goa KL (2000) Zolpidem: an update of its pharmacology, therapeutic efficacy and tolerability in the treatment of insomnia. Drugs 59:865–889

    Article  CAS  PubMed  Google Scholar 

  5. Maarek L, Cramer P, Attali P, Coquelin JP, Morselli PL (1992) The safety and efficacy of zolpidem in insomniac patients: a long-term open study in general practice. J Int Med Res 20:162–170. https://doi.org/10.1177/030006059202000208

    Article  CAS  PubMed  Google Scholar 

  6. Walsh JK, Roth T, Randazzo A et al (2000) Eight weeks of non-nightly use of zolpidem for primary insomnia. Sleep 23:1087–1096

    Article  CAS  PubMed  Google Scholar 

  7. Dundar Y, Boland A, Strobl J et al (2004) Newer hypnotic drugs for the short-term management of insomnia: a systematic review and economic evaluation. Health Technol Assess 8:iii–iix 1–125

    Article  CAS  PubMed  Google Scholar 

  8. Kang D-Y, Park S, Rhee C-W, Kim YJ, Choi NK, Lee J, Park BJ (2012) Zolpidem use and risk of fracture in elderly insomnia patients. J Prev Med Public Health 45:219–226. https://doi.org/10.3961/jpmph.2012.45.4.219

    Article  PubMed  PubMed Central  Google Scholar 

  9. Berry SD, Lee Y, Cai S, Dore DD (2013) Nonbenzodiazepine sleep medication use and hip fractures in nursing home residents. JAMA Intern Med 173:754–761. https://doi.org/10.1001/jamainternmed.2013.3795

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Yang Y-H, Lai J-N, Lee C-H, Wang J-D, Chen P-C (2011) Increased risk of hospitalization related to motor vehicle accidents among people taking zolpidem: a case-crossover study. J Epidemiol 21:37–43

    Article  PubMed  PubMed Central  Google Scholar 

  11. Brodeur MR, Stirling AL (2001) Delirium associated with zolpidem. Ann Pharmacother 35:1562–1564. https://doi.org/10.1345/aph.10385

    Article  CAS  PubMed  Google Scholar 

  12. Aragona M (2000) Abuse, dependence, and epileptic seizures after zolpidem withdrawal: review and case report. Clin Neuropharmacol 23:281–283

    Article  CAS  PubMed  Google Scholar 

  13. Cubała WJ, Landowski J (2007) Seizure following sudden zolpidem withdrawal. Prog Neuro-Psychopharmacol Biol Psychiatry 31:539–540. https://doi.org/10.1016/j.pnpbp.2006.07.009

    Article  CAS  Google Scholar 

  14. Victorri-Vigneau C, Dailly E, Veyrac G, Jolliet P (2007) Evidence of zolpidem abuse and dependence: results of the French Centre for Evaluation and Information on Pharmacodependence (CEIP) network survey. Br J Clin Pharmacol 64:198–209. https://doi.org/10.1111/j.1365-2125.2007.02861.x

    Article  PubMed  PubMed Central  Google Scholar 

  15. Hajak G, Müller WE, Wittchen HU, Pittrow D, Kirch W (2003) Abuse and dependence potential for the non-benzodiazepine hypnotics zolpidem and zopiclone: a review of case reports and epidemiological data. Addiction 98:1371–1378

    Article  CAS  PubMed  Google Scholar 

  16. Kapil V, Green JL, Le Lait C, Wood DM, Dargan PI (2014) Misuse of benzodiazepines and Z-drugs in the UK. Br J Psychiatry 205:407–408. https://doi.org/10.1192/bjp.bp.114.149252

    Article  CAS  PubMed  Google Scholar 

  17. Andersen ABT, Frydenberg M (2011) Long-term use of zopiclone, zolpidem and zaleplon among Danish elderly and the association with sociodemographic factors and use of other drugs. Pharmacoepidemiol Drug Saf 20:378–385. https://doi.org/10.1002/pds.2104

    Article  CAS  PubMed  Google Scholar 

  18. Omvik S, Pallesen S, Bjorvatn B, Sivertsen B, Havik OE, Nordhus IH (2010) Patient characteristics and predictors of sleep medication use. Int Clin Psychopharmacol 25:91–100. https://doi.org/10.1097/YIC.0b013e328334e5e6

    Article  PubMed  Google Scholar 

  19. Ohayon MM (2002) Epidemiology of insomnia: what we know and what we still need to learn. Sleep Med Rev 6:97–111

    Article  PubMed  Google Scholar 

  20. Mulvale G, Hurley J (2008) Insurance coverage and the treatment of mental illness: effect on medication and provider use. J Ment Health Policy Econ 11:177–199

    PubMed  Google Scholar 

  21. 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 

  22. Lai M-M, Lin C-C, Lin C-C, Liu C-S, Li T-C, Kao C-H (2014) Long-term use of zolpidem increases the risk of major injury: a population-based cohort study. Mayo Clin Proc 89:589–594. https://doi.org/10.1016/j.mayocp.2014.01.021

    Article  CAS  PubMed  Google Scholar 

  23. Chen P-L, Lee W-J, Sun W-Z, Oyang Y-J, Fuh J-L (2012) Risk of dementia in patients with insomnia and long-term use of hypnotics: a population-based retrospective cohort study. PLoS One 7:e49113. https://doi.org/10.1371/journal.pone.0049113

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Hoffmann F, Pfannkuche M, Glaeske G (2008) High usage of zolpidem and zopiclone. Cross-sectional study using claims data. Nervenarzt 79:67–72. https://doi.org/10.1007/s00115-007-2280-6

    Article  CAS  PubMed  Google Scholar 

  25. Hsiao F-Y, Hsieh P-H, Gau C-S (2013) Ten-year trend in prescriptions of z-hypnotics among the elderly: a nationwide, cross-sectional study in Taiwan. Journal of Clinical Gerontology and Geriatrics 4:37–41. https://doi.org/10.1016/j.jcgg.2012.12.001

    Article  Google Scholar 

  26. Johnsen MT, Wynn R, Bratlid T (2012) Is there a negative impact of winter on mental distress and sleeping problems in the subarctic: the Tromsø study. BMC Psychiatry 12:225. https://doi.org/10.1186/1471-244X-12-225

    Article  PubMed  PubMed Central  Google Scholar 

  27. Morin CM, LeBlanc M, Daley M, Gregoire JP, Mérette C (2006) Epidemiology of insomnia: prevalence, self-help treatments, consultations, and determinants of help-seeking behaviors. Sleep Med 7:123–130. https://doi.org/10.1016/j.sleep.2005.08.008

    Article  CAS  PubMed  Google Scholar 

  28. Ohayon MM, Hong S-C (2002) Prevalence of insomnia and associated factors in South Korea. J Psychosom Res 53:593–600

    Article  PubMed  Google Scholar 

  29. Hausken AM, Furu K, Skurtveit S, Engeland A, Bramness JG (2009) Starting insomnia treatment: the use of benzodiazepines versus z-hypnotics. A prescription database study of predictors. Eur J Clin Pharmacol 65:295–301. https://doi.org/10.1007/s00228-008-0565-8

    Article  CAS  PubMed  Google Scholar 

  30. Kim C Prescription drugs for 300 days? Long term prescriptions that hold patients hostage make patients sick. hankookilbo. Available at: http://www.hankookilbo.com/v/2357613cc8904733b9992e18279dabde. Accessed August 9, 2017

  31. Kesselheim AS, Donneyong M, Dal Pan GJ, Zhou EH, Avorn J, Schneeweiss S, Seeger JD (2017) Changes in prescribing and healthcare resource utilization after FDA drug safety communications involving zolpidem-containing medications. Pharmacoepidemiol Drug Saf 26:712–721. https://doi.org/10.1002/pds.4215

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This study used National Health Insurance Service (NHIS)—National Sample Cohort data (REQ0000006111) made available by the NHIS.

Funding

This research was supported by Korea-Canada Cooperative Development Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (MSIT) (No.2017K1A3A1A12073341).

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Correspondence to Ju-Young Shin.

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The authors declare that they have no conflict of interest.

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Key points

1. The usage of zolpidem is dramatically increased by approximately 18 times since zolpidem was authorized in the market (1181 in 2002 vs. 21,399 in 2013).

2. Reimbursement guidelines in Korea recommend that zolpidem is used for a maximum duration of 30 days.

3. Zolpidem was prescribed for over 30 days in 8.3% of treatment episodes.

4. The odds of zolpidem prescription for over 30 days were higher for older patients, women, and prescriptions from tertiary hospitals.

5. The odds of zolpidem prescription for over 30 days were higher for the immediate release form than the controlled release form.

Yunjeung Jang and Inmyung Song are Co-first author

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Jang, Y., Song, I., Oh, IS. et al. Twelve-year trend in the use of zolpidem and physicians’ non-compliance with recommended duration: a Korean national health insurance database study. Eur J Clin Pharmacol 75, 109–117 (2019). https://doi.org/10.1007/s00228-018-2563-9

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  • DOI: https://doi.org/10.1007/s00228-018-2563-9

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