Skip to main content
SpringerLink
Log in

Abuse and Misuse of Pregabalin and Gabapentin

  • Systematic Review
  • Published:
Drugs Aims and scope Submit manuscript

Abstract

Background

Gabapentinoid (pregabalin and gabapentin) abuse is increasingly being reported.

Objective

To assess the extent of gabapentinoid abuse, characteristics of typical abusers, patterns of abuse, and potential harms in order to bring this trend to providers’ attention.

Methods

A systematic review of MEDLINE, Cochrane Library, ClinicalTrials.gov, and US FDA data, indexed through 28 July 2016, utilizing the following searches: pregabalin OR gabapentin OR gabapentinoid AND one of the following: abuse, misuse, overdose, or substance-related disorders[MESH], was conducted. Additional studies were identified through review of references. English-language epidemiological studies, clinical studies, and case reports/series of gabapentinoid abuse/misuse/overdose were included. The authors reached consensus regarding study inclusion after full-text review. The body of literature was assessed for bias qualitatively.

Results

Fifty-nine studies were included in this systematic review (24 epidemiological, three clinical abuse liability, 16 abuse/misuse/dependence case reports/series, 17 acute overdose case reports/series—one included both an epidemiological study and case series and was included in both counts). Analysis of these studies indicates increasing numbers of patients are self-administering higher than recommended doses to achieve euphoric highs. In the general population, a 1.6% prevalence of gabapentinoid abuse was observed, whereas prevalence ranged from 3% to 68% among opioid abusers. An international adverse event database identified 11,940 reports of gabapentinoid abuse from 2004–2015, with >75% reported since 2012. Risk factors include a history of substance abuse, particularly opioids, and psychiatric co-morbidities. While effects of excessively high doses are generally non-lethal, gabapentinoids are increasingly being identified in post-mortem toxicology analyses.

Conclusion

Evidence suggests gabapentinoids possess potential for abuse, particularly in individuals with a history of opioid abuse, and reports of such abuse are increasingly being documented. Prescribers should be aware of high-risk populations and monitor for signs of abuse.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Volkow ND. National Institute of Health National Institute on Drug Abuse. https://www.drugabuse.gov/publications/research-reports/prescription-drugs/director. Accessed 30 May 2016.

  2. National Institutes of Health. How Many People Abuse Prescription Drugs? https://www.drugabuse.gov/publications/research-reports/prescription-drugs/trends-in-prescription-drug-abuse/how-many-people-abuse-prescription-drugs. Accessed 16 June 2016.

  3. Rudd RA, Aleshire N, Zibbell JE, Gladden RM. Centers for disease control. increase in drug and opioid overdose deaths—USA, 2000–2014. Morbid Mortal Wkly Rep. 2016;64(50):1378–82.

    Article  Google Scholar 

  4. Bastiaens L, Galus J, Mazur C. Abuse of gabapentin is associated with opioid addiction. Psychiatr Q. 2016. (Epub ahead of print).

  5. Neurontin® [package insert]. New York: Pfizer, Inc.; 2015.

  6. Lexi-Drugs. Lexicomp. Hudson: Wolters Kluwer Health, Inc. http://online.lexi.com. Accessed 6/12/16.

  7. Lyrica® [package insert]. New York: Pfizer, Inc. 2016.

  8. Martinotti G. Pregabalin in clinical psychiatry and addiction: pros and cons. Expert Opin Investig Drugs. 2012;21(9):1243–5.

    Article  CAS  PubMed  Google Scholar 

  9. Bockbrader HN, Wesche D, Miller R, Chapel S, Janiczek N, Burger P. A comparison of the pharmacokinetics and pharmacodynamics of pregabalin and gabapentin. Clin Pharmacokinet. 2010;49:661–9.

    Article  CAS  PubMed  Google Scholar 

  10. Baird CR, Fox P, Colvin LA. Gabapentinoid abuse in order to potentiate the effect of methadone: a survey among substance misusers. Eur Addict Res. 2014;20(3):115–8.

    Article  PubMed  Google Scholar 

  11. Schwan S, Sundström 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.

    Article  PubMed  Google Scholar 

  12. Papazisis G, Tzachanis D. Pregabalin’s abuse potential: a mini review focusing on the pharmacological profile. Int J Clin Pharmacol Ther. 2014;52(8):709–16.

    Article  CAS  PubMed  Google Scholar 

  13. Schifano F. Misuse and abuse of pregabalin and gabapentin: cause for concern? CNS Drugs. 2014;28:491–6.

    Article  CAS  PubMed  Google Scholar 

  14. Kruszewski SP, Paczynski RP, Kahn DA. Gabapentin-induced delirium and dependence. J Psychiatr Pract. 2009;15(4):314–9.

    Article  PubMed  Google Scholar 

  15. Pittinger C, Desan PH. Gabapentin abuse, and delirium tremens upon gabapentin withdrawal. J Clin Psychiatry. 2007;68(3):483–4.

    Article  Google Scholar 

  16. Grosshans M, Lemenager T, Vollmert C. Pregabalin abuse among opiate addicted patients. Eur J Clin Pharmacol. 2013;69(12):2021–5.

    Article  CAS  PubMed  Google Scholar 

  17. Fischer JH, Barr AN, Rogers SL, Fischer PA, Trudeau VL. Lack of serious toxicity following gabapentin overdose. Neurology. 1994;44:937–8.

    Article  Google Scholar 

  18. Schifano F, D’Offizi S, Piccione M, Corazza O, Deluca P, Davey Z, et al. Is there a recreational misuse potential for pregabalin? Analysis of anecdotal online reports in comparison with related gabapentin and clonazepam data. Psychother Psychosom. 2011;80(2):118–22.

    Article  PubMed  Google Scholar 

  19. 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.

    Article  PubMed  Google Scholar 

  20. Häkkinen M, Vuori E, Kalso E, Gergov M, Ojanperä I. Profiles of pregabalin and gabapentin abuse by postmortem toxicology. Forensic Sci Int. 2014;241:1–6.

    Article  PubMed  Google Scholar 

  21. Smith RV, Lofwall MR, Havens JR. Abuse and diversion of gabapentin among nonmedical prescription opioid users in Appalachian Kentucky. Am J Psychiatry. 2015;172(5):487–8.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Kapil V, Green JL, Le Lait MC, Wood DM, Dargan PI. Misuse of the γ-aminobutyric acid analogues baclofen, gabapentin and pregabalin in the UK. Br J Clin Pharmacol. 2014;78(1):190–1.

    Article  CAS  PubMed  Google Scholar 

  23. Wills B, Reynolds P, Chu E, Murphy C, Cumpston K, Stromberg P, et al. Clinical outcomes in newer anticonvulsant overdose: a poison center observational study. J Med Toxicol. 2014;10(3):254–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Smith BH, Higgins C, Baldacchino A, Kidd B, Bannister J. Substance misuse of gabapentin. Br J Gen Pract. 2012;62(601):406–7.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Spence D. Bad medicine: gabapentin and pregabalin. BMJ. 2013;347:f6747.

    Article  PubMed  Google Scholar 

  26. Lottner-Nau S, Ovguer B, Paul LD, Graw M, Sachs H, Roider G. Abuse of pregabalin—results of the postmortem toxicology from 2010–2012. Toxichem Krimtech. 2013;80:339.

    Google Scholar 

  27. Smith SM, Dart RC, Katz NP, Paillard F, Adams EH, Comer SD, et al. Classification and definition of misuse, abuse, and related events in clinical trials: ACTTION systematic review and recommendations. Pain. 2013;154:2287–96.

    Article  PubMed  Google Scholar 

  28. 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. (Epub ahead of print).

  29. Jonsson B, Backman E, Salmonson H, Höjer J. Injection of crushed tablets—a prospective observational study. Clin Toxicol (Phila). 2014;52(9):982–3.

    Article  PubMed  Google Scholar 

  30. Launiainen T, Broms U, Keskitalo-Vuokko K, Pitkäniemi J, Pelander A, Kaprio J, et al. Nicotine, alcohol, and drug findings in young adults in a population-based postmortem database. Nicotine Tob Res. 2011;13(9):763–71.

    Article  CAS  PubMed  Google Scholar 

  31. Asomaning K, Abramsky S, Liu Q, Zhou X, Sobel RE, Watt S. Pregabalin prescriptions in the UK: a drug utilization study of The Health Improvement Network (THIN) primary care database. Int J Clin Pract. 2016;70(5):380–8.

    Article  CAS  PubMed  Google Scholar 

  32. Schjerning O, Pottegård A, Damkier P, Rosenzweig M, Nielsen J. Use of pregabalin—a nationwide pharmacoepidemiological drug utilization study with focus on abuse potential. Pharmacopsychiatry. 2016. (Epub ahead of print).

  33. McNamara S, Stokes S, Kilduff R, Shine A. Pregabalin abuse amongst opioid substitution treatment patients. Ir Med J. 2015;108(10):309–10.

    CAS  PubMed  Google Scholar 

  34. Bodén R, Wettermark B, Brandt L, Kieler H. Factors associated with pregabalin dispensing at higher than the approved maximum dose. Eur J Clin Pharmacol. 2014;70(2):197–204.

    Article  PubMed  Google Scholar 

  35. Eastwood JA, Davison E. Pregabalin concentrations in post-mortem blood—a two year study. Forensic Sci Int. 2016;266:197–201.

    Article  CAS  PubMed  Google Scholar 

  36. Bossard JB, Ponte C, Dupouy J, Lapeyre-Mestre M, Jouanjus E. Disproportionality analysis for the assessment of abuse and dependence potential of pregabalin in the French pharmacovigilance database. Clin Drug Investig. 2016. (Epub ahead of print).

  37. Gahr M, Freudenmann RW, Hiemke C, Kölle MA, Schönfeldt-Lecuona C. Pregabalin abuse and dependence in Germany: results from a database query. Eur J Clin Pharmacol. 2013;69(6):1335–42.

    Article  PubMed  Google Scholar 

  38. Alblooshi H, Hulse GK, El Kashef A, Al Hashmi H, Shawky M, Al Ghaferi H, et al. The pattern of substance use disorder in the United Arab Emirates in 2015: results of a National Rehabilitation Centre cohort study. Subst Abuse Treat Prev Policy. 2016;11:19.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Caster O, Edwards IR, Norén GN, Lindquist M. Earlier discovery of pregabalin’s dependence potential might have been possible. Eur J Clin Pharmacol. 2011;67(3):319–20.

    Article  PubMed  Google Scholar 

  40. Zacny JP, Paice JA, Coalson DW. Subjective, psychomotor, and physiological effects of pregabalin alone and in combination with oxycodone in healthy volunteers. Pharmacol Biochem Behav. 2012;100(3):560–5.

    Article  CAS  PubMed  Google Scholar 

  41. Lile JA, Wesley MJ, Kelly TH, Hays LR. Separate and combined effects of gabapentin and [INCREMENT]9-tetrahydrocannabinol in humans discriminating [INCREMENT]9-tetrahydrocannabinol. Behav Pharmacol. 2016;27:215–24.

    Article  CAS  PubMed  Google Scholar 

  42. Reccoppa L, Malcolm R, Ware M. Gabapentin abuse in inmates with prior history of cocaine dependence. Am J Addict. 2004;13(3):321–3.

    Article  PubMed  Google Scholar 

  43. Millar J, Sadasivan S, Weatherup N, Lutton S. Lyrica nights–recreational pregabalin abuse in an urban emergency department. Emery Med J. 2013;30:874.

    Google Scholar 

  44. Markowitz JS, Finkenbine R, Myrick H, King L, Carson WH. Gabapentin abuse in a cocaine user: implications for treatment? J Clin Psychopharmacol. 1997;17(5):423–4.

    Article  CAS  PubMed  Google Scholar 

  45. Reeves RR, Ladner ME. Potentiation of the effect of buprenorphine/naloxone with gabapentin or quetiapine. Am J Psychiatry. 2014;171(6):691.

    Article  PubMed  Google Scholar 

  46. Reeves RR, Burke RS. Abuse of combinations of gabapentin and quetiapine. Prim Care Companion CNS Disord. 2014;16(5). doi:10.4088/PCC.14l01660.

  47. Halaby A, Kassm SA, Naja WJ. Pregabalin dependence: a case report. Curr Drug Saf. 2015;10(2):184–6.

    Article  PubMed  Google Scholar 

  48. Satish R, Kandasamy A, Jayarajan D, Benegal V. Gabapentin dependence in a patient with opioid dependence syndrome. J Neuropsychiatry Clin Neurosci. 2015;27(1):e64.

    Article  PubMed  Google Scholar 

  49. Papazisis G, Garyfallos G, Sardeli C, Kouvelas D. Pregabalin abuse after past substance-seeking behavior. Int J Clin Pharmacol Ther. 2013;51(5):441–2.

    Article  PubMed  Google Scholar 

  50. Gahr M, Franke B, Freudenmann RW, Kölle MA, Schönfeldt-Lecuona C. Concerns about pregabalin: further experience with its potential of causing addictive behaviors. J Addict Med. 2013;7(2):147–9.

    Article  CAS  PubMed  Google Scholar 

  51. Carrus D, Schifano F. Pregabalin misuse-related issues; intake of large dosages, drug-smoking allegations, and possible association with myositis: two case reports. J Clin Psychopharmacol. 2012;32(6):839–40.

    Article  PubMed  Google Scholar 

  52. Filipetto FA, Zipp CP, Coren JS. Potential for pregabalin abuse or diversion after past drug-seeking behavior. J Am Osteopath Assoc. 2010;110(10):605–7.

    PubMed  Google Scholar 

  53. Grosshans M, Mutschler J, Hermann D, Klein O, Dressing H, Kiefer F, et al. Pregabalin abuse, dependence, and withdrawal: a case report. Am J Psychiatry. 2010;167(7):869.

    Article  PubMed  Google Scholar 

  54. Victorri-Vigneau C, Guerlais M, Jolliet P. Abuse, dependency and withdrawal with gabapentin: a first case report. Pharmacopsychiatry. 2007;40(1):43–4.

    Article  CAS  PubMed  Google Scholar 

  55. Rohman L, Hebron A. Acute dystonic reaction caused by gabapentin. J Emerg Med. 2014;46:e89.

    Article  PubMed  Google Scholar 

  56. Klein-Schwartz W, Shepherd JG, Gorman S, Dahl B. Characterization of gabapentin overdose using a poison center case series. J Toxicol Clin Toxicol. 2003;41(1):11–5.

    Article  CAS  PubMed  Google Scholar 

  57. Moore KA, Levine B, Fowler D. A fatality involving metaxalone. Forensic Sci Int. 2005;149:249–51.

    Article  PubMed  Google Scholar 

  58. Fernandez MC, Walter FG, Peterson LR, Walkotte SM. Gabapentin, valproic acid, and ethanol intoxication: elevated blood levels with mild clinical effects. Clin Toxicol. 1996;34(4):437–9.

    CAS  Google Scholar 

  59. Stopforth J. Overdose with gabapentin and lamotrigine. SAMJ. 1997;87(10):1388.

    CAS  PubMed  Google Scholar 

  60. Middleton O. Suicide by gabapentin overdose. J Forensic Sci. 2011;56(5):1373–5.

    Article  CAS  PubMed  Google Scholar 

  61. Schauer SG, Varney SM. Gabapentin overdose in a military beneficiary. Mil Med. 2013;178(1):e133–5.

    Article  PubMed  Google Scholar 

  62. Miljevic CD, Crnobaric C, Nikolic S, Lecic-Tosevski D. A case of pregabalin intoxication. Psychiatriki. 2012;23(2):162–5.

    CAS  PubMed  Google Scholar 

  63. Spiller HA, Dunaway MD, Cutino L. Massive gabapentin and presumptive quetiapine overdose. Vet Hum Toxicol. 2002;44(4):243–4.

    PubMed  Google Scholar 

  64. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  65. Braga AJ, Chidley K. Self-poisoning with lamotrigine and pregabalin. Anaesthesia. 2007;62(5):524–7.

    Article  CAS  PubMed  Google Scholar 

  66. Spiller HA, Bratcher R, Griffith JR. Pregabalin overdose with benign outcome. Clin Toxicol (Phila). 2008;46(9):917.

    Article  PubMed  Google Scholar 

  67. Cantrell FL, Mena O, Gary RD, McIntyre IM. An acute gabapentin fatality: a case report with postmortem concentrations. Int J Legal Med. 2015;129:771–5.

    Article  PubMed  Google Scholar 

  68. Rasimas JJ, Burkhart KK. Cardiac conduction disturbances after an overdose of nefazodone and gabapentin. Am J Emerg Med. 2006;24:886–8.

    Article  PubMed  Google Scholar 

  69. Koschny R, Lutz M, Seckinger J, Schwenger V, Stremmel W, Eisenbach C. Extracorporeal life support and plasmapheresis in a case of severe polyintoxication. J Emerg Med. 2014;47(5):527–31.

    Article  PubMed  Google Scholar 

  70. Roberge RJ, Francis EH III. Use of naloxone in valproic acid overdose: case report and review. J Emerg Med. 2002;22:67–70.

    Article  PubMed  Google Scholar 

  71. Saar E, Beyer J, Gerostamoulos D, Drummer OH. The time-dependent post-mortem redistribution of antipsychotic drugs. Forensic Sci Int. 2012;222:223–7.

    Article  CAS  PubMed  Google Scholar 

  72. Berry D, Millington C. Analysis of pregabalin at the therapeutic concentrations in human plasma/serum by reversed-phase HPLC. Ther Drug Monit. 2005;27:451–6.

    Article  CAS  PubMed  Google Scholar 

  73. Schulz M, Iwersen-Bergmann S, Andresen H, Schmoldt A. Therapeutic and toxic blood concentrations of nearly 1000 drugs and other xenobiotics. Crit Care. 2012;16:R136.

    Article  PubMed  PubMed Central  Google Scholar 

  74. Zaccara G, Gangemi P, Perucca P, Specchio L. The adverse event profile of pregabalin: a systematic review and meta-analysis of randomized controlled trials. Epilepsia. 2011;52(4):826–36.

    Article  CAS  PubMed  Google Scholar 

  75. Piskorska B, Miziak B, Czuczwar SJ, et al. Safety issues around misuse of antiepileptics. Expert Opin Drug Saf. 2013;12(5):647–57.

    Article  CAS  PubMed  Google Scholar 

  76. Bicknell M. The pain of pregabalin prescribing in prisons. Br J Gen Pract. 2013;63(613):405.

    Article  PubMed  PubMed Central  Google Scholar 

  77. Del Paggio D. Bay area psychopharmacology. Newsletter. 2005;8(2):1–5. http://www.acbhcs.org/Psychopharmacology/2005/June2005.pdf.

  78. Mah L, Hart M. Gabapentin withdrawal: case report in an older adult and review of the literature. J Am Geriatr Soc 2013;61(9):1635–7.

    Article  PubMed  Google Scholar 

  79. See S, Hendriks E, Hsiung L. Akathisia induced by gabapentin withdrawal. Ann Pharmacother. 2011;45:e31.

    Article  PubMed  Google Scholar 

  80. Hellwig TR, Hammerquist R, Termaat J. Withdrawal symptoms after gabapentin discontinuation. Am J Health Syst Pharm. 2010;67:910–2.

    Article  PubMed  Google Scholar 

  81. Verma A, St. Clair EW, Radtke RA. A case of sustained massive gabapentin overdose without serious side effects. Ther Drug Monit. 1999;21(6):615.

    Article  CAS  PubMed  Google Scholar 

  82. Howland RH. Gabapentin for substance use disorders: is it safe and appropriate? J Psychosoc Nurs Ment Health Serv. 2014;52(2):13–6.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. College of Pharmacy, The University of Texas at Austin, 7703 Floyd Curl Dr., MC 6220, San Antonio, TX, 78229-3900, USA

    Kirk E. Evoy, Megan D. Morrison & Stephen R. Saklad

  2. University Health System, 1055 Ada Street, San Antonio, TX, 78223, USA

    Kirk E. Evoy

Authors
  1. Kirk E. Evoy
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Megan D. Morrison
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Stephen R. Saklad
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kirk E. Evoy.

Ethics declarations

Funding

The authors did not receive any funding for this study.

Conflict of interest

Steven Saklad declares the following: Employee of The University of Texas at Austin College of Pharmacy. Appointed to the Texas Department of State Health Services, San Antonio State Hospital and the UT Health Science Center San Antonio School of Medicine. Speakers bureau for Otsuka/Lundbeck. Consultant for NCS Pearson, and Takeda. Speaker for several professional organizations. Board of Directors for the College of Psychiatric and Neurologic Pharmacists Foundation. Business Development Council for the College of Psychiatric and Neurologic Pharmacists. Expert witness on both defendant and plaintiff sides. No direct stock ownership in pharmaceutical corporations. Kirk Evoy and Megan Morrison report no conflicts of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Evoy, K.E., Morrison, M.D. & Saklad, S.R. Abuse and Misuse of Pregabalin and Gabapentin. Drugs 77, 403–426 (2017). https://doi.org/10.1007/s40265-017-0700-x

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40265-017-0700-x

Keywords

Search

Navigation