Advertisement

CNS Drugs

, Volume 24, Issue 7, pp 611–620 | Cite as

Assessment of abuse potential of benzodiazepines from a prescription database using ‘doctor shopping’ as an indicator

  • Vincent Pradel
  • Catherine Delga
  • Frank Rouby
  • Joëlle Micallef
  • Maryse Lapeyre-MestreEmail author
Original Research Article

Abstract

Background: Benzodiazepines are widely used for different purposes because of their pharmacological properties, but their abuse potential may represent a limitation to their use. Data suggest that this abuse potential may vary between products and available dosages. Doctor shopping (the simultaneous use of several physicians by a patient) is one of the most important ways in which prescription drugs, in particular benzodiazepines, are diverted.

Objective: To assess the potential for abuse of several benzodiazepines using doctor shopping in a French administrative area as a proxy for abuse.

Methods: All prescriptions reimbursed during the year 2003 in Haute-Garonne, France (one million inhabitants) for benzodiazepines that were available in ambulatory care through community pharmacies as solid oral forms were extracted from a reimbursement database. The benzodiazepines were alprazolam (0.25 mg, 0.50 mg), bromazepam 6 mg, clonazepam 2mg, clorazepate (5mg, 10 mg, 50 mg), diazepam (1 mg, 5 mg, 10 mg), flunitrazepam 1 mg, lorazepam (1 mg, 2.5 mg) and tetrazepam 50 mg. For each patient, the quantities prescribed, dispensed and obtained by doctor shopping (i.e. overlap between prescriptions from different prescribers) were computed. Benzodiazepines were compared using their ‘doctor shopping indicator’ (DSI, the percentage of each drug obtained through doctor shopping among the total reimbursed quantity).

Results: About 128 000 patients received at least one benzodiazepine during the year. Four groups of benzodiazepines were identified according to their abuse potential: very high abuse potential (flunitrazepam, DSI = 42.8%); high abuse potential (diazepam 10 mg, DSI = 3.2%; clorazepate 50 mg, DSI = 2.7%); intermediate abuse potential (alprazolam 0.50 mg, bromazepam, clonazepam, DSI ranging from 1.8% to 1.9%); and low abuse potential (other benzodiazepines and dosages, DSI ranging from 0.3% to 1.1%).

Conclusion: The DSI can be used to assess the relative abuse liability of benzodiazepines and to detect signals of new patterns of abuse in settings where centralized records of prescription or deliveries are available for the great majority of patients.

Keywords

Buprenorphine Community Pharmacy Alprazolam Clonazepam Define Daily Dose 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

The authors would like to acknowledge Dr Robert Bourrel, practitioner at the Regional Medical Department of the French Health Insurance System (Caisse Nationale d’Assurance Maladie des Travailleurs Salariés) for giving access to the data, and Pascale Morandi for editing the manuscript.

None of the authors has any conflict of interest to declare in relation to this work. There was no specific funding for the study and the preparation of the manuscript. The CEIP annually receives funds from the Afssaps (the French Medicine Agency) to collect data and to perform studies about abuse and dependence of any psychoactive drugs. The Unit of Pharmacoepidemiology, EA 3696 annually receives funds from the French Ministry of Research.

References

  1. 1.
    Ator NA, Griffiths RR. Principles of drug abuse liability assessment in laboratory animals. Drug Alcohol Depend 2003; 70(3 Suppl. ): S55–72PubMedCrossRefGoogle Scholar
  2. 2.
    EMA. Guidelines on the non clinical investigation of the dependence potential of medicinal products: EMEA/ CHMP/SWP/94227/2004, March 2006, 1–12 [online]. Available from URL: http://www.ema.europa.eu/pdfs/human/ewp/36996305en.pdf [Accessed 2010 May 20]
  3. 3.
    Balster RL, Bigelow GE. Guidelines and methodological reviews concerning drug abuse liability assessment. Drug Alcohol Depend 2003; 70: S13–40PubMedCrossRefGoogle Scholar
  4. 4.
    Brady KT, Lydiard RB, Brady JV. Assessing abuse liability in clinical trials. Drug Alcohol Depend 2003; 70(3 Suppl. ): S87–95PubMedCrossRefGoogle Scholar
  5. 5.
    Comer SD, Ashworth JB, Foltin RW, et al. The role of human drug self-administration procedures in the development of medications. Drug Alcohol Depend 2008; 96: 1–15PubMedCrossRefGoogle Scholar
  6. 6.
    Gerada C, Ashworth M. ABC of mental health: addiction and dependence. I: illicit drugs. BMJ 1997; 315: 297–300Google Scholar
  7. 7.
    Malcolm R, Brady KT, Johnston AL, et al. Types of benzodiazepines abused by chemically dependent inpatients. J Psychoactive Drugs 1993; 25: 315–9PubMedCrossRefGoogle Scholar
  8. 8.
    Fry CL, Bruno RB. Recent trends in benzodiazepine use by injecting drug users in Victoria and Tasmania. Drug Alcohol Rev 2002; 21: 363–7PubMedCrossRefGoogle Scholar
  9. 9.
    Jaffe JH, Bloor R, Crome I, et al. A postmarketing study of relative abuse liability of hypnotic sedative drugs. Addiction 2004; 99: 165–73PubMedCrossRefGoogle Scholar
  10. 10.
    Barrau K, Thirion X, Micallef J, et al. Comparison of methadone and high dosage buprenorphine users in French care centres. Addiction 2001; 96: 1433–41PubMedCrossRefGoogle Scholar
  11. 11.
    Thirion X, Micallef J, Barrau K, et al. Observation of psychoactive substance consumption: methods and results of the French OPPIDUM programme. Eur Addict Res 2001; 7: 32–6PubMedCrossRefGoogle Scholar
  12. 12.
    Degenhardt L, Roxburgh A, van Beek I, et al. The effects of the market withdrawal of temazepam gel capsules on benzodiazepine injecting in Sydney, Australia. Drug Alcohol Rev 2008; 27: 145–51PubMedCrossRefGoogle Scholar
  13. 13.
    Drug Abuse Warning Network (DAWN) [online]. Available from URL: http://dawninfo.samhsa.gov/ [Accessed 2010 May 3]
  14. 14.
    Thirion X, Lapierre V, Micallef J, et al. Buprenorphine prescription by general practitioners in a French region. Drug Alcohol Depend 2002; 65: 197–204PubMedCrossRefGoogle Scholar
  15. 15.
    Sajan A, Corneil T, Grzybowski S. The street value of prescription drugs. CMAJ 1998; 159: 139–42PubMedGoogle Scholar
  16. 16.
    O’Brien CP. Benzodiazepine use, abuse, and dependence. J Clin Psychiatry 2005; 66: 28–33PubMedCrossRefGoogle Scholar
  17. 17.
    Bergman U, Dahl-Puustinen ML. Use of prescription forgeries in a drug abuse surveillance network. Eur J Clin Pharmacol 1989; 36: 621–3PubMedCrossRefGoogle Scholar
  18. 18.
    Boeuf O, Lapeyre-Mestre M; French Network of Centers for Evaluation and Information Pharmacodependence (CEIP). Survey of forged prescriptions to investigate risk of psychoactive medications abuse in France: results of OSIAP survey. Drug Saf 2007; 30: 265–76PubMedCrossRefGoogle Scholar
  19. 19.
    Inciardi JA, Surratt HL, Kurtz SP, et al. Mechanisms of prescription drug diversion among drug-involved club and street-based populations. Pain Med 2007; 8: 171–83PubMedCrossRefGoogle Scholar
  20. 20.
    Martyres RF, Clode D, Burns JM. Seeking drugs or seeking help? Escalating “doctor shopping” by young heroin users before fatal overdose. Med J Aust 2004; 180: 211–4PubMedGoogle Scholar
  21. 21.
    Pradel V, Thirion X, Ronfle E, et al. Assessment of doctor-shopping for high dosage buprenorphine maintenance treatment in a French region: development of a new method for prescription database. Pharmacoepidemiol Drug Saf 2004; 13: 473–81PubMedCrossRefGoogle Scholar
  22. 22.
    Pradel V, Frauger E, Thirion X, et al. Impact of a prescription monitoring program on doctor-shopping for high dosage buprenorphine. Pharmacoepidemiol Drug Saf 2009; 18: 36–43PubMedCrossRefGoogle Scholar
  23. 23.
    Griffiths RR, Johnson MW. Relative abuse liability of hypnotic drugs: a conceptual framework and algorithm for differentiating among compounds. J Clin Psychiatry 2005; 66 Suppl. 9: 31–41Google Scholar
  24. 24.
    Lapeyre-Mestre M, Llau ME, Gony M, et al. Opiate maintenance with buprenorphine in ambulatory care: a 24-week follow-up study of new users. Drug Alcohol Depend 2003; 72: 297–303PubMedCrossRefGoogle Scholar
  25. 25.
    Isacson D, Carsjö K, Bergman U, et al. Long-term use of benzodiazepines in a Swedish community: an eight-year follow-up. J Clin Epidemiol 1992; 45: 429–36PubMedCrossRefGoogle Scholar
  26. 26.
    Egan M, Moride Y, Wolfson C, et al. Long-term continuous use of benzodiazepines by older adults in Quebec: prevalence, incidence and risk factors. J Am Geriatr Soc 2000; 48: 811–6PubMedGoogle Scholar
  27. 27.
    van Hulten R, Isacson D, Bakker A, et al. Comparing patterns of long-term benzodiazepine use between a Dutch and a Swedish community. Pharmacoepidemiol Drug Saf 2003; 12: 49–53PubMedCrossRefGoogle Scholar
  28. 28.
    Fourrier A, Letenneur L, Dartigues J, et al. Benzodiazepine use in an elderly community-dwelling population: characteristics of users and factors associated with subsequent use. Eur J Clin Pharmacol 2001; 57: 419–25PubMedCrossRefGoogle Scholar
  29. 29.
    Lagnaoui R, Depont F, Fourrier A, et al. Patterns and correlates of benzodiazepine use in the French general population. Eur J Clin Pharmacol 2004; 60: 523–9PubMedCrossRefGoogle Scholar
  30. 30.
    Who Collaborating Centre for Drug Statistics Methodology. ATC/DDD index [online]. Available from URL: http://www.whocc.no/atcddd/ [Accessed 2010 Mar 29]
  31. 31.
    International Narcotics Control Board. Defined daily doses for statistical purposes (S-DDD) for psychotropic substances [online]. Available from URL: http://www.incb.org/pdf/e/tr/psy/2003/psychotropics_table3.pdf [Accessed 2010 Mar 29]
  32. 32.
    Woods JH, Winger G. Abuse liability of flunitrazepam. J Clin Psychopharmacol 1997; 17(3 Suppl. 2): 1S–57SPubMedCrossRefGoogle Scholar
  33. 33.
    Frauger E, Pradel V, Natali F, et al. Misuse of clonazepam (Rivotril): recent trends. Therapie 2006; 61: 49–55PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2010

Authors and Affiliations

  • Vincent Pradel
    • 1
    • 2
  • Catherine Delga
    • 3
  • Frank Rouby
    • 1
  • Joëlle Micallef
    • 1
    • 4
  • Maryse Lapeyre-Mestre
    • 3
    • 5
    Email author
  1. 1.Centre d’Evaluation et d’Information sur la Pharmacodépendance CEIP PACA-Corse, centre associéService de Pharmacologie CliniqueMarseilleFrance
  2. 2.Laboratoire de Santé PubliqueMarseilleFrance
  3. 3.Unité de Pharmacoépidémiologie, Faculté de MédecineUniversité de ToulouseToulouseFrance
  4. 4.Institut des Neurosciences Cognitives de la Méditerranée, Faculté de MédecineUniversité de la Méditerranée-CNRSMarseilleFrance
  5. 5.Centre d’Evaluation et d’Information sur la Pharmacodépendance Addictovigilance CEIP Midi-PyrénéesService de Pharmacologie CliniqueToulouseFrance

Personalised recommendations