Advertisement

Clinical Drug Investigation

, Volume 38, Issue 4, pp 373–380 | Cite as

Intentional Drug Overdose Involving Pregabalin and Gabapentin: Findings from the National Self-Harm Registry Ireland, 2007–2015

  • Caroline DalyEmail author
  • Eve Griffin
  • Darren M. Ashcroft
  • Roger T. Webb
  • Ivan J. Perry
  • Ella Arensman
short communication

Abstract

Introduction

Intentional drug overdose (IDO) is a significant public health problem. Concerns about the misuse of gabapentinoids, i.e. pregabalin and gabapentin, including their consumption in IDO have grown in recent years. This paper examines the trends in the prevalence of gabapentinoids taken in IDO, the profile of individuals taking them, and associated overdose characteristics.

Methods

Presentations to emergency departments involving IDO, recorded by the National Self-Harm Registry Ireland between 1 January 2007 and 31 December 2015 were examined. Data items included patient demographics, drug names, total tablet quantity consumed and alcohol involvement.

Results

Gabapentinoids were involved in 2115 (2.9%) of the 72,391 IDOs recorded. Presentations involving a gabapentinoid increased proportionally from 0.5% in 2007 to 5.5% in 2015. The majority of IDOs involving a gabapentinoid were made by females (59.9%), with over one-third (37.2%) involving alcohol. Compared with IDOs involving other drugs, presentations with a gabapentinoid were made by persons who were older (median 37 vs. 32 years) and involved a significantly greater median quantity of tablets (30 vs. 21, p ≤ 0.001), with over one-quarter (27.4%) of these involving the ingestion of 50 tablets or more. Admission to hospital was significantly more common following IDOs with a gabapentinoid compared with those without (49.4% vs. 41.4%, p ≤ 0.001).

Conclusions

This study identified the increasing use of gabapentinoids in IDO, describing the profile and overdose characteristics of presentations. It is important for clinicians to exercise vigilance while prescribing gabapentinoids, including being aware of other medications that their patients may have access to. Our findings support the need for routine monitoring for signs of misuse among those prescribed gabapentinoids.

Notes

Acknowledgements

The authors would like to thank the DROs who work on the National Self-Harm Registry Ireland, collecting information on self-harm presentations to hospitals across Ireland.

Funding

This research was conducted as part of a Ph.D. that was jointly funded by the University of Manchester and the National Suicide Research Foundation, Cork, Ireland. The National Self-Harm Registry Ireland is funded by the Health Service Executive’s National Office for Suicide Prevention.

Compliance and Ethical Standards

Conflict of interest

Ms. Caroline Daly, Dr Eve Griffin, Prof. Darren M. Ashcroft, Prof. Roger T. Webb, Prof Ivan J. Perry and Prof Ella Arensman have no conflicts of interest to declare.

Ethics Approval

The National Self-Harm Registry Ireland has received ethical approval from the National Research Ethics Committee of the Faculty of Public Health Medicine and the Clinical Research Ethics Committees of all 36 hospitals. The National Suicide Research Foundation is registered with the Data Protection Agency and complies with the Irish Data Protection Act of 1988 and the Irish Data Protection (Amendment) Act of 2003.

Supplementary material

40261_2017_616_MOESM1_ESM.pdf (52 kb)
Supplementary material 1 (PDF 51 kb)

References

  1. 1.
    Griffin E, Corcoran P, Cassidy L, O’Carroll A, Perry IJ, Bonner B. Characteristics of hospital-treated intentional drug overdose in Ireland and Northern Ireland. BMJ Open. 2014;4(7):e005557.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Hawton K, Haw C, Casey D, Bale L, Brand F, Rutherford D. Self-harm in Oxford, England: epidemiological and clinical trends, 1996–2010. Soc Psychiatry Psychiatr Epidemiol. 2015;50(5):695–704.CrossRefPubMedGoogle Scholar
  3. 3.
    Hawton K, Bergen H, Cooper J, Turnbull P, Waters K, Ness J, et al. Suicide following self-harm: findings from the Multicentre Study of self-harm in England, 2000–2012. J Affect Disord. 2015;175:147–51.CrossRefPubMedGoogle Scholar
  4. 4.
    Hawton K, Saunders K, Topiwala A, Haw C. Psychiatric disorders in patients presenting to hospital following self-harm: a systematic review. J Affect Disord. 2013;151(3):821–30.CrossRefPubMedGoogle Scholar
  5. 5.
    Cooper J, Kapur N, Dunning J, Guthrie E, Appleby L, Mackway-Jones K. A clinical tool for assessing risk after self-harm. Ann Emerg Med. 2006;48(4):459–66.CrossRefPubMedGoogle Scholar
  6. 6.
    Hawton K, Bergen H, Casey D, Simkin S, Palmer B, Cooper J, et al. Self-harm in England: a tale of three cities. Multicentre study of self-harm. Soc Psychiatry Psychiatr Epidemiol. 2007;42(7):513–21.CrossRefPubMedGoogle Scholar
  7. 7.
    Perry IJ, Corcoran P, Fitzgerald AP, Keeley HS, Reulbach U, Arensman E. The incidence and repetition of hospital-treated deliberate self harm: findings from the world’s first national registry. PLoS One. 2012;7(2):e31663.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Ness J, Hawton K, Bergen H, Cooper J, Steeg S, Kapur N, et al. Alcohol use and misuse, self-harm and subsequent mortality: an epidemiological and longitudinal study from the multicentre study of self-harm in England. Emerg Med J. 2015;32(10):793–9.CrossRefPubMedGoogle Scholar
  9. 9.
    Bergen H, Hawton K, Waters K, Cooper J, Kapur N. Epidemiology and trends in non-fatal self-harm in three centres in England: 2000–2007. Br J Psychiatry. 2010;197(6):493–8.CrossRefPubMedGoogle Scholar
  10. 10.
    Corcoran PHB, Griffin E, Perry IJ, Arensman E. Psychotropic medication involved in intentional drug overdose: implications for treatment. Neuropsychiatry. 2013;3(3):285–93.CrossRefGoogle Scholar
  11. 11.
    Townsend EHK, Harriss L, Bale E, Bond A. Substances used in deliberate self-poisoning 1985–1997: trends and associations with age, gender, repetition and suicide intent. Soc Psychiatry Psychiatr Epidemiol. 2001;36(5):228–34.CrossRefPubMedGoogle Scholar
  12. 12.
    Baldessarini RJ, Leahy L, Arcona S, Gause D, Zhang W, Hennen J. Patterns of psychotropic drug prescription for U.S. patients with diagnoses of bipolar disorders. Psychiatr Serv. 2007;58(1):85–91.CrossRefPubMedGoogle Scholar
  13. 13.
    Spina E, Perugi G. Antiepileptic drugs: indications other than epilepsy. Epileptic Disord. 2004;6(2):57–75.PubMedGoogle Scholar
  14. 14.
    Italiano D, Capuano A, Alibrandi A, Ferrara R, Cannata A, Trifiro G, et al. Indications of newer and older anti-epileptic drug use: findings from a southern Italian general practice setting from 2005–2011. Br J Clin Pharmacol. 2015;79(6):1010–9.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Goodman CW, Brett AS. Gabapentin and pregabalin for pain—is increased prescribing a cause for concern? N Engl J Med. 2017;377(5):411–4.CrossRefPubMedGoogle Scholar
  16. 16.
    Kharasch ED, Eisenach JC. Wherefore gabapentinoids? Was there rush too soon to judgment? Anesthesiology. 2016;124(1):10–2.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Evoy KE, Morrison MD, Saklad SR. Abuse and misuse of pregabalin and gabapentin. Drugs. 2017;77(4):403–26.CrossRefPubMedGoogle Scholar
  18. 18.
    Schwan S, Sundstrom A, Stjernberg E, Hallberg E, Hallberg P. A signal for an abuse liability for pregabalin: results from the Swedish spontaneous adverse drug reaction reporting system. Eur J Clin Pharmacol. 2010;66(9):947–53.CrossRefPubMedGoogle Scholar
  19. 19.
    Public Health England and National Health Service England. Advice for prescribers on the risk of the misuse of pregabalin and gabapentin. 2014. Available at: http://guildfordadvancedcourses.co.uk/wp-content/uploads/2017/10/PHE-2014.pdf. Accessed 1 Sept 2017.
  20. 20.
    Elliott SP, Burke T, Smith C. Determining the toxicological significance of pregabalin in fatalities. J Forensic Sci. 2017;62(1):169–73.CrossRefPubMedGoogle Scholar
  21. 21.
    Schifano F. Misuse and abuse of pregabalin and gabapentin: cause for concern? CNS Drugs. 2014;28(6):491–6.CrossRefPubMedGoogle Scholar
  22. 22.
    Chiappini S, Schifano F. A decade of gabapentinoid misuse: an analysis of the european medicines agency’s ‘Suspected Adverse Drug Reactions’ database. CNS Drugs. 2016;30(7):647–54.CrossRefPubMedGoogle Scholar
  23. 23.
    Lyndon A, Audrey S, Wells C, Burnell ES, Ingle S, Hill R, et al. Risk to heroin users of polydrug use of pregabalin or gabapentin. Addiction. 2017;112(9):1580–9.CrossRefPubMedGoogle Scholar
  24. 24.
    Simonsen KW, Edvardsen HM, Thelander G, Ojanpera I, Thordardottir S, Andersen LV, et al. Fatal poisoning in drug addicts in the Nordic countries in 2012. Forensic Sci Int. 2015;248:172–80.CrossRefPubMedGoogle Scholar
  25. 25.
    Abrahamsson T, Berge J, Ojehagen A, Hakansson A. Benzodiazepine, z-drug and pregabalin prescriptions and mortality among patients in opioid maintenance treatment-A nation-wide register-based open cohort study. Drug Alcohol Depend. 2017;174:58–64.CrossRefPubMedGoogle Scholar
  26. 26.
    Frauger E, Pochard L, Boucherie Q, Giocanti A, Chevallier C, Daveluy A, et al. Surveillance system on drug abuse: interest of the French national OPPIDUM program of French addictovigilance network [in French]. Therapie. 2017;72(4):491–501.CrossRefPubMedGoogle Scholar
  27. 27.
    McNamara S, Stokes S, Kilduff R, Shine A. Pregabalin abuse amongst opioid substitution treatment patients. Ir Med J. 2015;108(10):309–10.PubMedGoogle Scholar
  28. 28.
    Hakkinen M, Vuori E, Kalso E, Gergov M, Ojanpera I. Profiles of pregabalin and gabapentin abuse by postmortem toxicology. Forensic Sci Int. 2014;241:1–6.CrossRefPubMedGoogle Scholar
  29. 29.
    Bronstein AC, Spyker DA, Cantilena LR Jr, Green J, Rumack BH, Heard SE. 2006 Annual report of the american association of poison control centers’ national poison data system (NPDS). Clin Toxicol (Phila). 2007;45(8):815–917.CrossRefGoogle Scholar
  30. 30.
    Litovitz TL, Klein-Schwartz W, White S, Cobaugh DJ, Youniss J, Omslaer JC, et al. 2000 Annual report of the american association of poison control centers toxic exposure surveillance system. Am J Emerg Med. 2001;19(5):337–95.CrossRefPubMedGoogle Scholar
  31. 31.
    Wood DM, Berry DJ, Glover G, Eastwood J, Dargan PI. Significant pregabalin toxicity managed with supportive care alone. J Med Toxicol. 2010;6(4):435–7.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Nixon AC, Doak MW, Crozier H, Crooks DP, Waring WS. Patterns of antiepileptic drug overdose differ between men and women: admissions to the Edinburgh Poisons Unit, 2000–2007. QJM. 2009;102(1):51–6.CrossRefPubMedGoogle Scholar
  33. 33.
    Office for National Statistics. Deaths related to drug poisoning in England and Wales: 2016 registrations. 2017. Available at: https://www.ons.gov.uk/peoplepopulationandcommunity/birthsdeathsandmarriages/deaths/bulletins/deathsrelatedtodrugpoisoninginenglandandwales/2016registrations. Accessed 1 Sept 2017.
  34. 34.
    Health Research Board. National Drug-Related Deaths Index, 2004 to 2014 data. 2014. Available at: http://www.hrb.ie/uploads/tx_hrbpublications/National_Drug-Related_Deaths_Index_2004_to_2014_data_01.pdf. Accessed 18 Dec 2017.
  35. 35.
    Schjerning O, Rosenzweig M, Pottegard A, Damkier P, Nielsen J. Abuse potential of pregabalin: a systematic review. CNS Drugs. 2016;30(1):9–25.CrossRefPubMedGoogle Scholar
  36. 36.
    Wilens T, Zulauf C, Ryland D, Carrellas N, Catalina-Wellington I. Prescription medication misuse among opioid dependent patients seeking inpatient detoxification. Am J Addict. 2015;24(2):173–7.CrossRefPubMedGoogle Scholar
  37. 37.
    Grosshans M, Lemenager T, Vollmert C, Kaemmerer N, Schreiner R, Mutschler J, et al. Pregabalin abuse among opiate addicted patients. Eur J Clin Pharmacol. 2013;69(12):2021–5.CrossRefPubMedGoogle Scholar
  38. 38.
    Schjerning O, Pottegard A, Damkier P, Rosenzweig M, Nielsen J. Use of pregabalin: a nationwide pharmacoepidemiological drug utilization study with focus on abuse potential. Pharmacopsychiatry. 2016;49(4):155–61.CrossRefPubMedGoogle Scholar
  39. 39.
    Health and Social Care Information Centre. Prescription Cost Analysis England 2012-Prescription items dispensed in the community in England and listed alphabetically within chemical entity by therapeutic class. 2013. Available at: https://digital.nhs.uk/catalogue/PUB10610. Accessed 1 Sept 2017.
  40. 40.
    Savica R, Beghi E, Mazzaglia G, Innocenti F, Brignoli O, Cricelli C, et al. Prescribing patterns of antiepileptic drugs in Italy: a nationwide population-based study in the years 2000–2005. Eur J Neurol. 2007;14(12):1317–21.CrossRefPubMedGoogle Scholar
  41. 41.
    US FDA. Statistical review and evaluation-Antiepileptic drugs and suicidality. 2008. Available at: https://www.fda.gov/ohrms/dockets/ac/08/briefing/2008-4372b1-01-FDA.pdf. Accessed 1 Sept 2017.
  42. 42.
    EMCDDA-Europol 2009 Annual Report on the implementation of Council Decision 2005/387/JHA; Annex 2 – New psychoactive substances reported to the EMCDDA and Europol for the first time in 2009 under the terms of Council. Available at: http://www.emcdda.europa.eu/html.cfm/index33227EN.html. Accessed 1 Sept 2017.
  43. 43.
    Health and Social Care Board. Advice for prescribers on the risk of the misuse of pregabalin and gabapentin. 2015. Available at: http://niformulary.hscni.net/Formulary/Adult/PDF/PregabalinAndGabapentinRiskOfMisuseAdviceHSCBWebVersion.pdf. Accessed 1 Sept 2017.
  44. 44.
    Home Office and the Health Service Executive. A consultation on proposals to schedule pregabalin and gabapentin under the Misuse of Drugs Regulations 2001. 2017. Available at: https://www.gov.uk/government/consultations/pregabalin-and-gabapentin-proposal-to-schedule-under-the-misuse-of-drugs-regulations-2001. Accessed 1 Sept 2017.
  45. 45.
    World Health Organization. Collaborating Centre for Drug Statistics Methodology, Guidelines for ATC classification and DDD assignment. 2017. Available at: https://www.whocc.no/filearchive/publications/2017_guidelines_web.pdf. Accessed 1 Nov 2017.
  46. 46.
    Finkelstein Y, Macdonald EM, Hollands S, Sivilotti ML, Hutson JR, Mamdani MM, et al. Repetition of intentional drug overdose: a population-based study. Clin Toxicol (Phila). 2016;54(7):585–9.CrossRefGoogle Scholar
  47. 47.
    de Groot MC, Schuerch M, de Vries F, Hesse U, Oliva B, Gil M, et al. Antiepileptic drug use in seven electronic health record databases in Europe: a methodologic comparison. Epilepsia. 2014;55(5):666–73.CrossRefPubMedGoogle Scholar
  48. 48.
    Bazazi AR, Zelenev A, Fu JJ, Yee I, Kamarulzaman A, Altice FL. High prevalence of non-fatal overdose among people who inject drugs in Malaysia: correlates of overdose and implications for overdose prevention from a cross-sectional study. Int J Drug Policy. 2015;26(7):675–81.CrossRefPubMedGoogle Scholar
  49. 49.
    Haw C, Hawton K, Casey D, Bale E, Shepherd A. Alcohol dependence, excessive drinking and deliberate self-harm: trends and patterns in Oxford, 1989–2002. Soc Psychiatry Psychiatr Epidemiol. 2005;40(12):964–71.CrossRefPubMedGoogle Scholar
  50. 50.
    Sinclair JM, Gray A, Hawton K. Systematic review of resource utilization in the hospital management of deliberate self-harm. Psychol Med. 2006;36(12):1681–93.CrossRefPubMedGoogle Scholar
  51. 51.
    Bonnet U, Scherbaum N. How addictive are gabapentin and pregabalin? A systematic review. Eur Neuropsychopharmacol. 2017;27(12):1185–215.CrossRefPubMedGoogle Scholar
  52. 52.
    Haw C, Casey D, Holmes J, Hawton K. Suicidal intent and method of self-harm: a large-scale study of self-harm patients presenting to a general hospital. Suicide Life Threat Behav. 2015;45(6):732–46.CrossRefPubMedGoogle Scholar
  53. 53.
    Hori S, Kinoshita K. Clinical characteristics of patients who overdose on multiple psychotropic drugs in Tokyo. J Toxicol Sci. 2016;41(6):765–73.CrossRefPubMedGoogle Scholar
  54. 54.
    Crombie IK, McLoone P. Does the availability of prescribed drugs affect rates of self poisoning? Br J Gen Pract. 1998;48(433):1505–6.PubMedPubMedCentralGoogle Scholar
  55. 55.
    Gjelsvik B, Heyerdahl F, Hawton K. Prescribed medication availability and deliberate self-poisoning: a longitudinal study. J Clin Psychiatry. 2012;73(4):e548–54.CrossRefPubMedGoogle Scholar
  56. 56.
    Tournier M, Grolleau A, Cougnard A, Molimard M, Verdoux H. Factors associated with choice of psychotropic drugs used for intentional drug overdose. Eur Arch Psychiatry Clin Neurosci. 2009;259(2):86–91.CrossRefPubMedGoogle Scholar
  57. 57.
    Okumura Y, Nishi D. Risk of recurrent overdose associated with prescribing patterns of psychotropic medications after nonfatal overdose. Neuropsychiatr Dis Treat. 2017;13:653–65.CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Zalsman G, Hawton K, Wasserman D, van Heeringen K, Arensman E, Sarchiapone M, et al. Suicide prevention strategies revisited: 10-year systematic review. Lancet Psychiatry. 2016;3(7):646–59.CrossRefPubMedGoogle Scholar
  59. 59.
    Health Service Executive. Connecting for Life, Irelands National Strategy to Reduce Suicide 2015–2020. 2015. Available at: https://www.healthpromotion.ie/hp-files/docs/HME00945.pdf. Accessed 1 Sept 2017.
  60. 60.
    World Health Organization. Practice manual for establishing and maintaining surveillance systems for suicide attempts and self-harm. 2016. Available at: http://apps.who.int/iris/bitstream/10665/208895/1/9789241549578_eng.pdf. Accessed 1 Sept 2017.

Copyright information

© Springer International Publishing AG, part of Springer Nature 2017

Authors and Affiliations

  1. 1.National Suicide Research FoundationUniversity College CorkCorkIreland
  2. 2.Centre for Pharmacoepidemiology and Drug Safety, Division of Pharmacy and Optometry, School of Health Sciences, Faculty of Biology, Medicine and HealthUniversity of Manchester, Manchester Academic Health Sciences Centre (MAHSC)ManchesterUK
  3. 3.NIHR Greater Manchester Patient Safety Translational Research CentreUniversity of Manchester, Manchester Academic Health Sciences Centre (MAHSC)ManchesterUK
  4. 4.Centre for Mental Health and Safety, Division of Psychology and Mental Health, School of Health Sciences, Faculty of Biology, Medicine and HealthUniversity of Manchester, Manchester Academic Health Sciences Centre (MAHSC)ManchesterUK
  5. 5.School of Public HealthUniversity College CorkCorkIreland

Personalised recommendations