Pharmacoepidemiological characterisation of zolpidem and zopiclone usage



Zolpidem and zopiclone are two widely used non-benzodiazepine hypnotics whose usage seems to be associated to pharmacodependence. However, to our knowledge, there has as yet been no published epidemiological study which has compared their abuse or dependence potential. We used a pharmacoepidemiological approach to identify and characterise zolpidem and zopiclone users in real life situations.


Regular users of zolpidem or zopiclone were identified in the database of a French regional health insurance organisation. A latent class analysis (LCA) was used to identify different subgroups of users of these two hypnotics.


The study cohort comprised 25,168 patients who regularly used zolpidem and 21,860 who regularly used zopiclone. The results of the latent class analysis, which enables subgroups with similar patterns of response to be identified, revealed four clinical subtypes of users of zolpidem: non-problematic users, users with associations with hypnotics/anxiolytics or with associated mental disorders, and problematic users. Only three subgroups were identified for zopiclone, and LCA did not discriminate a special class of problematic users for this drug.


Our analysis indicates that there is a subclass of zolpidem user suggestive of abuse; this was not the case for zopiclone. This methodology is very interesting because it allows analysis of databases and determination of a specific signature of drugs potentially leading to abuse or dependence.

This is a preview of subscription content, log in to check access.

Fig. 1
Fig. 2


  1. 1.

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

    PubMed  Article  CAS  Google Scholar 

  2. 2.

    LRP (2002) Dependance aux hypnotiques: zolpidem et zopiclone aussi. Rev Prescr 20:675–676

    Google Scholar 

  3. 3.

    LRP (2002) Zolpidem : classé comme psychotrope à risque d’abus. Rev Prescr 22:819

    Google Scholar 

  4. 4.

    Briot M (2006) Report on the appropriate use of psychotropic drugs in France. Assemblée Nationale, ISSN 1249-3872; no. 3187. Office Parlementaire d’Evaluation des Politiques de Santé, Assemblée Nationale, Paris

  5. 5.

    Frauger E, Pauly V, Natali F et al (2011) Patterns of methylphenidate use and assessment of its abuse and diversion in two French administrative areas using a proxy of deviant behaviour determined from a reimbursement database: main trends from 2005 to 2008. CNS Drugs 25(5):415–424

    PubMed  Article  Google Scholar 

  6. 6.

    Frauger E, Pauly V, Thirion X et al (2009) Estimation of clonazepam abuse liability: a new method using a reimbursed drug database. Int Clin Psychopharmacol 24(6):318–324

    PubMed  Article  Google Scholar 

  7. 7.

    Micaleff J, Jolliet P, Victorri-Vigneau C et al (2008) First meeting of the French CEIP (centres d’evaluation et d’information sur la pharmacodependance). Assessment of the abuse and pharmacodependence potential during drug development. Therapie 63(1):55–65

    PubMed  Article  Google Scholar 

  8. 8.

    Pauly V, Pradel V, Frauger E et al (2011) Evolution of opioids reimbursement since 2004 from the National Database of the General Health Insurance System. Therapie 66(4):369–372

    PubMed  Article  Google Scholar 

  9. 9.

    Pradel V, Frauger E, Thirion X et al (2009) Impact of a prescription monitoring program on doctor-shopping for high dosage buprenorphine. Pharmacoepidemiol Drug Saf 18(1):36–43

    PubMed  Article  Google Scholar 

  10. 10.

    Victorri-Vigneau C, Larour K, Simon D et al (2009) Creating and validating a tool able to detect fraud by prescription falsification from health insurance administration databases. Therapie 64(1):27–31

    PubMed  Article  Google Scholar 

  11. 11.

    Victorri-Vigneau C, Sebille V, Gerardin M et al (2011) Epidemiological characterization of drug overconsumption: the example of antidepressants. J Addict Dis 30(4):342–350

    PubMed  Article  Google Scholar 

  12. 12.

    Wainstein L, Victorri-Vigneau C, Sebille V et al (2011) Pharmacoepidemiological characterization of psychotropic drugs consumption using a latent class analysis. Int Clin Psychopharmacol 26(1):54–62

    PubMed  Article  Google Scholar 

  13. 13.

    McCutcheon (1987) Latent class analysis. Sage university paper series on quantitative applications in the social sciences. Series no. 07-064. Sage, Newbury Park

  14. 14.

    Moss HB, Chen CM, Yi HY (2007) Subtypes of alcohol dependence in a nationally representative sample. Drug Alcohol Depend 91(2–3):149–158

    PubMed  Article  Google Scholar 

  15. 15.

    Reboussin BA, Song EY, Shrestha A et al (2006) A latent class analysis of underage problem drinking: evidence from a community sample of 16–20 year olds. Drug Alcohol Depend 83(3):199–209

    PubMed  Article  Google Scholar 

  16. 16.

    Agrawal A, Lynskey MT, Madden PA et al (2007) A latent class analysis of illicit drug abuse/dependence: results from the National Epidemiological Survey on Alcohol and Related Conditions. Addiction 102(1):94–104

    PubMed  Article  Google Scholar 

  17. 17.

    Martin-Latry K, Begaud B (2010) Pharmacoepidemiological research using French reimbursement databases: yes we can! Pharmacoepidemiol Drug Saf 19(3):256–265

    PubMed  Article  Google Scholar 

  18. 18.

    Latry P, Molimard M, Begaud B et al (2010) How reimbursement databases can be used to support drug utilisation studies: example using the main French national health insurance system database. Eur J Clin Pharmacol 66(7):743–748

    PubMed  Article  CAS  Google Scholar 

  19. 19.

    Victorri-Vigneau C, Dailly E, Veyrac G et al (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(2):198–209

    PubMed  Article  Google Scholar 

  20. 20.

    Krueger TH, Kropp S, Huber TJ (2005) High-dose zolpidem dependence in a patient with chronic facial pain. Ann Pharmacother 39(4):773–774

    PubMed  Article  Google Scholar 

  21. 21.

    Sethi PK, Khandelwal DC (2005) Zolpidem at supratherapeutic doses can cause drug abuse, dependence and withdrawal seizure. J Assoc Physicians India 53:139–140

    PubMed  CAS  Google Scholar 

  22. 22.

    Quaglio G, Lugoboni F, Fornasiero A et al (2005) Dependence on zolpidem: two case reports of detoxification with flumazenil infusion. Int Clin Psychopharmacol 20(5):285–287

    PubMed  Article  Google Scholar 

  23. 23.

    Brunelle E, Rotily M, Lancon C et al (2005) Zolpidem: intravenous misuse in drug abusers. Addiction 100(9):1377–1378

    PubMed  Article  Google Scholar 

  24. 24.

    Liappas IA, Papageorgiou CC, Rabavilas AD (2006) Abnormal auditory N400 in a case of zolpidem dependence, during a working memory test. Eur Psychiatry 21(2):135–137

    PubMed  Article  Google Scholar 

  25. 25.

    Djezzar S, Dugarin J, Dally S (2006) Zolpidem and dextromoramide abuse with increased metabolism. Am J Addict 15(5):405–406

    PubMed  Article  Google Scholar 

  26. 26.

    Cubala WJ, Landowski J (2007) Seizure following sudden zolpidem withdrawal. Prog Neuropsychopharmacol Biol Psychiatry 31(2):539–540

    PubMed  Article  CAS  Google Scholar 

  27. 27.

    Askew JP (2007) Zolpidem addiction in a pregnant woman with a history of second-trimester bleeding. Pharmacotherapy 27(2):306–308

    PubMed  Article  CAS  Google Scholar 

  28. 28.

    Huang MC, Lin HY, Chen CH (2007) Dependence on zolpidem. Psychiatry Clin Neurosci 61(2):207–208

    PubMed  Article  Google Scholar 

  29. 29.

    Mariani JJ, Levin FR (2007) Quetiapine treatment of zolpidem dependence. Am J Addict 16(5):426

    PubMed  Article  Google Scholar 

  30. 30.

    Benyamina A, Dublanchet O, Karila L et al (2007) Intravenous zolpidem abuse: a case for serotonin depletion. Am J Addict 16(6):534

    PubMed  Article  Google Scholar 

  31. 31.

    Svitek J, Heberlein A, Bleich S et al (2008) Extensive craving in high dose zolpidem dependency. Prog Neuropsychopharmacol Biol Psychiatry 32(2):591–592

    PubMed  Article  CAS  Google Scholar 

  32. 32.

    Sharan P, Bharadwaj R, Grover S et al (2007) Dependence syndrome and intoxication delirium associated with zolpidem. Natl Med J India 20(4):180–181

    PubMed  Google Scholar 

  33. 33.

    Jana AK, Arora M, Khess CR et al (2008) A case of zolpidem dependence successfully detoxified with clonazepam. Am J Addict 17(4):343–344

    PubMed  Article  Google Scholar 

  34. 34.

    Boucher A, Assaad S, Pariset C et al (2008) Digital ischemia following injection of a crushed tablet of zolpidem: tardive improvement with iloprost. Therapie 63(6):463–467

    PubMed  Article  Google Scholar 

  35. 35.

    Pitchot W, Ansseau M (2009) Zolpidem dependence and withdrawal seizure. Rev Med Liege 64(7–8):407–408

    PubMed  CAS  Google Scholar 

  36. 36.

    Chen CY, Shiah IS, Lee WK et al (2009) Dependence on quetiapine in combination with zolpidem and clonazepam in bipolar depression. Psychiatry Clin Neurosci 63(3):427–428

    PubMed  Article  Google Scholar 

  37. 37.

    Spyridi S, Diakogiannis I, Nimatoudis J et al (2009) Zolpidem dependence in a geriatric patient: a case report. J Am Geriatr Soc 57(10):1962–1963

    PubMed  Article  Google Scholar 

  38. 38.

    Damm J, Eser D, Moeller HJ et al (2010) Severe dependency on zolpidem in a patient with multiple sclerosis suffering from paraspasticity. World J Biol Psychiatry 11(2 Pt 2):516–518

    PubMed  Article  Google Scholar 

  39. 39.

    Aggarwal A, Sharma DD (2010) Zolpidem withdrawal delirium: a case report. J Neuropsychiatry Clin Neurosci 22(4):451-o.e27–451.e28

    Article  Google Scholar 

  40. 40.

    Wang LJ, Ree SC, Chu CL et al (2011) Zolpidem dependence and withdrawal seizure—report of two cases. Psychiatr Danub 23(1):76–78

    PubMed  Google Scholar 

  41. 41.

    Oulis P, Nakkas G, Masdrakis VG (2011) Pregabalin in zolpidem dependence and withdrawal. Clin Neuropharmacol 34(2):90–91

    PubMed  Google Scholar 

  42. 42.

    Cimolai N (2007) Zopiclone: is it a pharmacologic agent for abuse? Can Fam Physician 53(12):2124–2129

    PubMed  Google Scholar 

  43. 43.

    Hajak G, Muller WE, Wittchen HU et al (2003) Abuse and dependence potential for the non-benzodiazepine hypnotics zolpidem and zopiclone: a review of case reports and epidemiological data. Addiction 98(10):1371–1378

    PubMed  Article  CAS  Google Scholar 

  44. 44.

    Fung HT, Lai CH, Wong OF et al (2009) Hemolytic anemia after zopiclone overdose. Clin Toxicol (Phila) 47(9):902–903

    Article  CAS  Google Scholar 

  45. 45.

    Wong CP, Chiu PK, Chu LW (2005) Zopiclone withdrawal: an unusual cause of delirium in the elderly. Age Ageing 34(5):526–527

    PubMed  Article  Google Scholar 

  46. 46.

    Haasen C, Mueller-Thomsen T, Fink T et al (2005) Zopiclone dependence after insomnia related to torticollis. Int J Neuropsychopharmacol 8(2):309–310

    PubMed  Article  CAS  Google Scholar 

Download references

Conflict of interest

Pascale Jolliet declares consulting fees. Other authors declare that they have no conflict of interest.

Author information



Corresponding author

Correspondence to Caroline Victorri-Vigneau.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Victorri-Vigneau, C., Feuillet, F., Wainstein, L. et al. Pharmacoepidemiological characterisation of zolpidem and zopiclone usage. Eur J Clin Pharmacol 69, 1965–1972 (2013).

Download citation


  • Zolpidem
  • Zopiclone
  • Pharmacodependence
  • Abuse
  • Pharmacoepidemiology