Advertisement

European Journal of Clinical Pharmacology

, Volume 75, Issue 1, pp 77–85 | Cite as

Presentations to the emergency department with non-medical use of benzodiazepines and Z-drugs: profiling and relation to sales data

  • C . LyphoutEmail author
  • C. Yates
  • Z. R. Margolin
  • P. I. Dargan
  • A. M. Dines
  • F. Heyerdahl
  • K. E. Hovda
  • I. Giraudon
  • B. Bucher-Bartelson
  • J. L. Green
  • Euro-DEN Research Group
  • D. M. Wood
Pharmacoepidemiology and Prescription

Abstract

Background

Non-medical use of benzodiazepines and Z-drugs is common; however, there is limited information available on the extent of harm related to this in Europe, as well as the relationship between misuse and availability.

Aim

To describe presentations to the emergency department in Europe related to the recreational use of benzodiazepines and Z-drugs and compare regional differences in these presentations with legal drug sales of benzodiazepines and Z-drugs within each country.

Methods

Emergency department presentations with recreational misuse of benzodiazepines and Z-drugs were obtained from the Euro-DEN dataset for the period from October 2013 to September 2015; data extracted included demographics, clinical features, reported coused drugs, and outcome data. Sales figures obtained by QuintilesIMS™ (Atlanta, Georgia) were used to compare regional differences in the proportion of benzodiazepines and Z-drugs in the emergency department presentations and legal drug sales across Europe.

Results

Over the 2 years, there were 2119 presentations to the Euro-DEN project associated with recreational use of benzodiazepines and/or Z-drugs (19.3% of all Euro-DEN presentations). Presentations with 25 different benzodiazepines and Z-drugs were registered in all countries, most (1809/2340 registered benzodiazepines and Z-drugs, 77.3%) of which were prescription drugs. In 24.9%, the benzodiazepine was not specified. Where the benzodiazepine/Z-drug was known, the most frequently used benzodiazepines and Z-drugs were respectively clonazepam (29.5% of presentations), diazepam (19.9%), alprazolam (11.7%), and zopiclone (9.4%). The proportions of types of benzodiazepines/Z-drugs related to ED-presentations varied between countries. There was a moderate (Spain, UK, Switzerland) to high (France, Ireland, Norway) positive correlation between ED presentations and sales data (Spearman Row’s correlation 0.66–0.80, p < 0.005), with higher correlation in countries with higher ED presentation rates.

Conclusion

Presentations to the emergency department associated with the non-medical use of benzodiazepines and/or Z-drugs are common, with variation in the benzodiazepines and/or Z-drugs between countries. There was a moderate to high correlation with sales data, with higher correlation in countries with higher ED presentation rates. However, this is not the only explanation for the variation in non-medical use and in the harm associated with the non-medical use of benzodiazepines/Z-drugs.

Keywords

Acute toxicity Benzodiazepine Z-drug Prescription Emergency department Euro-DEN 

Notes

Funding information

The Euro-DEN Project was funded by the DPIP/ISEC Programme of the European Union; all of the authors had funding from the European Commission through the Euro-DEN project except ML and EL, whose costs were co-funded by the Swiss Centre of Applied Human Toxicology (SCAHT), and BB, JG, ZM, and CL.

Compliance with ethical standards

Conflict of interest

PD and DW have received financial and statistical support to undertake population and web monitoring studies on the non-medical use of prescription and non-prescription medicines in the UK and Singapore and travel and honorarium costs to attend and present at the Annual RADARS International Symposium and Scientific Meeting from the RADARS System, Denver Health and Hospital Authority, Denver, US.

Supplementary material

228_2018_2550_MOESM1_ESM.docx (26 kb)
Online Supplement 1 (DOCX 26 kb)
228_2018_2550_MOESM2_ESM.docx (116 kb)
Online Supplement 2 (DOCX 115 kb)

References

  1. 1.
    EMCDDA. Legal topic overviews: classification of controlled drugs. [Internet]. Lisbon; 2016. Available from: http://www.emcdda.europa.eu/html.cfm/index146601EN.html
  2. 2.
    Jones JD, Mogali S, Comer SD (2012) Polydrug abuse: a review of opioid and benzodiazepine combination use. Drug Alcohol Depend 125:8–18CrossRefGoogle Scholar
  3. 3.
    BNF. Hypnotics and anxiolytics [Internet]. 2013 [cited 2017 Dec 12]. Available from: https://www.bnf.org
  4. 4.
    Casati A, Sedefov R, Pfeiffer-Gerschel T (2012) Misuse of medicines in the European union: a systematic review of the literature. Eur Addict Res 18:228–245CrossRefGoogle Scholar
  5. 5.
    Gunja N (2013) The clinical and forensic toxicology of Z-drugs. J. Med. Toxicol. 9:155–162CrossRefGoogle Scholar
  6. 6.
    Home Office. The Misuse of Drugs Act 1971 (Modification) Order 2003. Br Med J. 2003;2–3. Available from: https://www.gov.uk/government/publications/controlled-drugs%2D%2D7
  7. 7.
    EMA. Zerene (zaleplon): Withdrawal of the marketing authorisation in the European Union. 2012Google Scholar
  8. 8.
    EMA. Sonata: withdrawal of the marketing authorisation in the European Union [Internet]. 2015. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/Public_statement/2015/10/WC500195873.pdf
  9. 9.
    United Nations Office on Drugs and Crime. The non-medical use of prescription drugs Policy direction issues [Internet]. Vienna; 2011. Available from: http://www.unodc.org/docs/youthnet/Final_Prescription_Drugs_Paper.pdf
  10. 10.
    Cole J, Chiarello R (1990) The benzodiazepines as drugs of abuse. J Psychiatr Res 24:135–144CrossRefGoogle Scholar
  11. 11.
    Griffiths R, Wolf B (1990) Relative abuse liability of different benzodiazepines in drug abusers. J Clin Psychopharmacol 10:237–243CrossRefGoogle Scholar
  12. 12.
    Zawertailo L, Busto U, Kaplan H, Greenblatt D, Sellers E (2003) Comparative abuse liability and pharmacological effects of meprobamate, triazolam, and butabarbital. J Clin Psychopharmacol 23:269–280Google Scholar
  13. 13.
    Abanades S, Farré M, Barral D, Torrens M, Neus Closas Y, Langohr K et al (2007) Relative abuse liability of +-hydroxybutyric acid, flunitrazepam, and ethanol in club drug users. J Clin Psychopharmacol 27:625–638CrossRefGoogle Scholar
  14. 14.
    Kapil V, Green J, Le Lait C, Wood D, Dargan P (2014) Misuse of benzodiazepines and Z-drugs in the UK. Br J Psychiatry 205:407–408CrossRefGoogle Scholar
  15. 15.
    Vijayaraghavan M, Freitas D, Miaskowskiel C, Kushel M (2014) Non-medical use of non-opioid psychotherapeutic medications in a community-based cohort of HIV-infected indigent adults. Drug Alcohol Depend 143:263–267CrossRefGoogle Scholar
  16. 16.
    EMCDDA. PERSPECTIVES ON DRUGS The misuse of benzodiazepines among high-risk opioid users in Europe [Internet]. 2015 [cited 2017 Jul 5]. Available from: http://www.emcdda.europa.eu/system/files/publications/2733/Misuse of benzos_POD2015.pdf
  17. 17.
    Vogel M, Knöpfli B, Schmid O, Prica M, Strasser J, Prieto L, Wiesbeck GA, Dürsteler-MacFarland KM (2013) Treatment or “high”: benzodiazepine use in patients on injectable heroin or oral opioids. Addict Behav 38:2477–2484CrossRefGoogle Scholar
  18. 18.
    Maddahian E, Newcomb MDBP (1986) Adolescents’ substance use: impact of ethnicity, income, and availability. Adv Alcohol Subst Abus 5:63–78CrossRefGoogle Scholar
  19. 19.
    Coffey C, Lynskey M, Wolfe R, Patton G (2000) Initiation and progression of cannabis use in a population-based Australian adolescent longitudinal study. Addiction 95:1679–1690CrossRefGoogle Scholar
  20. 20.
    Korf DJ (2002) Dutch coffee shops and trends in cannabis use. Addict Behav 27:851–866CrossRefGoogle Scholar
  21. 21.
    Dart RC, Surratt HL, Cicero TJ, Parrino MW, Severtson SG, Ph D et al (2015) Trends in opioid analgesic abuse and mortality in the United States. N Engl J Med 372:241–248CrossRefGoogle Scholar
  22. 22.
    The National Center on, Abuse A and S. UNDER THE COUNTER: THE DIVERSION AND ABUSE OF CONTROLLED PRESCRIPTION DRUGS IN THE U.S. [Internet]. Columbia; 2005. Available from: https://www.centeronaddiction.org/addiction-research/reports/under-counter-diversion-and-abuse-controlled-prescription-drugs-us
  23. 23.
    Wood DM, Heyerdahl F, Yates CB, Dines AM, Giraudon I, Hovda KE et al The European drug emergencies. Network (Euro-DEN)Google Scholar
  24. 24.
    Dines M, Wood D, Yates C, Heyerdahl F, Knut E, Giraudon I et al (2015) Acute recreational drug and new psychoactive substance toxicity in Europe: 12 months data collection from the European drug emergencies network (Euro-DEN). Clin Toxicol 53:893–900CrossRefGoogle Scholar
  25. 25.
    European Monitoring Centre for Drugs and Drug Addiction. Hospital emergency presentations and acute drug toxicity in Europe [Internet]. 2016. Available from: http://www.emcdda.europa.eu/system/files/publications/2973/TD0216713ENN-1_Final pdf.pdf
  26. 26.
    Yamamoto T. Euro-DEN analysis on emergency department presentations related to benzodiazepine and heroin use.Google Scholar
  27. 27.
    Moeller KE, Lee KC KJ. Urine drug screening: practical guide for clinicians. 2008;7231:66–76Google Scholar
  28. 28.
    Licata SC, Rowlett JK (2008) Abuse and dependence liability of benzodiazepine-type drugs: GABA-A receptor modulation and beyond. Pharmacol Biochem Behav 90:74–89CrossRefGoogle Scholar
  29. 29.
    Schuermeyer J, Salomonsen-Sautel S, Price RK, Balan S, Thurstone C, Min SJ, Sakai JT (2014) Temporal trends in marijuana attitudes, availability and use in Colorado compared to non-medical marijuana states: 2003-11. Drug alcohol depend. [Internet]. Elsevier Ireland Ltd 140:145–155 Available from:  https://doi.org/10.1016/j.drugalcdep.2014.04.016 Google Scholar
  30. 30.
    Daniulaityte R, Falck R, Carlson RG (2014) Sources of pharmaceutical opioids for non-medical use among young adults. J Psychoactive Drugs 46:198–207.  https://doi.org/10.1080/02791072.2014.916833 CrossRefGoogle Scholar
  31. 31.
    Wood DM, Dargan PI (2012) Understanding how data triangulation identifies acute toxicity of novel psychoactive drugs. J Med Toxicol 8:300–303CrossRefGoogle Scholar
  32. 32.
    Wood DM, Dargan P (2012) Novel psychoactive substances: how to understand the acute toxicity associated with the use of these substances. Ther Drug Monit 34:363–367CrossRefGoogle Scholar
  33. 33.
    Heyerdahl F, Hovda KE, Giraudon I, Yates C, Dines AM, Sedefov R et al (2014) Current European data collection on emergency department presentations with acute recreational drug toxicity: gaps and national variations. Clin Toxicol (Phila) 52:1005–1012Google Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • C . Lyphout
    • 1
    • 2
    Email author
  • C. Yates
    • 3
  • Z. R. Margolin
    • 4
  • P. I. Dargan
    • 1
    • 5
  • A. M. Dines
    • 1
  • F. Heyerdahl
    • 6
  • K. E. Hovda
    • 6
  • I. Giraudon
    • 7
  • B. Bucher-Bartelson
    • 4
  • J. L. Green
    • 4
    • 8
  • Euro-DEN Research Group
  • D. M. Wood
    • 1
    • 5
  1. 1.Clinical ToxicologyGuy’s and St Thomas’ Hospitals NHS Foundation Trust, and King’s Health PartnersLondonUK
  2. 2.Emergency DepartmentUniversity HospitalGhentBelgium
  3. 3.Emergency Department and Clinical Toxicology UnitHospital Universitari Son EspasesMallorcaSpain
  4. 4.Denver Health Rocky Mountain Poison & Drug CenterDenverUSA
  5. 5.Faculty of Life Sciences and MedicineKing’s College LondonLondonUK
  6. 6.The National CBRNe Centre of Medicine, Department of Acute Medicine, Medical DivisionOslo University HospitalOsloNorway
  7. 7.European Monitoring Centre for Drugs and Drug Addiction (EMCDDA)LisbonPortugal
  8. 8.Inflexxion, Inc.WalthamUSA

Personalised recommendations