A Decade of Gabapentinoid Misuse: An Analysis of the European Medicines Agency’s ‘Suspected Adverse Drug Reactions’ Database



The gabapentinoids pregabalin and gabapentin are being increasingly prescribed for a range of clinical conditions. Recently, although gabapentinoids at therapeutic dosages may present with low addictive liability levels, cases of misuse and rising numbers of related fatalities have been reported.


The aim of the study was to identify and assess cases of gabapentinoid misuse or dependence as reported to the European Medicines Agency’s EudraVigilance database, to identify the magnitude of this problem and the characteristics of these reactions.


All spontaneous reports of both gabapentin- (2004–2015) and pregabalin- (2006–2015) related misuse/abuse/dependence were retrieved. A descriptive analysis by source, sex, age, and type of report was performed.


From the EudraVigilance database 7639 (6.6 % of a total of 115,616) and 4301 (4.8 % of 90,166) adverse drug reaction reports of misuse/abuse/dependence were, respectively, associated with pregabalin and gabapentin, with an overall reporting frequency increasing over time. For both molecules, subjects typically involved were female adults. A total of 27 and 86 fatalities, respectively, associated with pregabalin and gabapentin, and mostly in combination with opioids, were identified. Analysis of proportional reporting ratios for drug abuse/dependence/intentional product misuse values seem to indicate that these adverse drug reactions were more frequently reported for pregabalin (1.25, 1.39, and 1.58, respectively) compared with gabapentin.


Despite data collection/methodological approach limitations, the present data seem to suggest that gabapentinoid misuse may be a cause for concern, especially in patients with a history of substance misuse. Hence, healthcare professionals should be vigilant when prescribing these molecules.

This is a preview of subscription content, access via your institution.

Fig. 1


  1. 1.

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

    Article  PubMed  Google Scholar 

  2. 2.

    Martinotti G, Lupi M, Sarchione F, et al. The potential of pregabalin in neurology, psychiatry and addiction: a qualitative overview. Curr Pharm Des. 2013;19:6367–74.

    CAS  Article  PubMed  Google Scholar 

  3. 3.

    Anonymous. Gabapentin and pregabalin: abuse and addiction. Prescrire Int. 2012;21:152–4.

  4. 4.

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

    CAS  Article  PubMed  Google Scholar 

  5. 5.

    Corkery J, Claridge H, Loi B, et al. Drug-related deaths in the UK: annual report 2013. Drug-related deaths reported by Coroners in England, Wales, Northern Ireland, Guernsey, Jersey and the Isle of Man; Police forces in Scotland; the Northern Ireland Statistics and Research Agency: annual report 2013 on deaths between January–December 2013. London: International Centre for Drug Policy, St George’s University of London. http://www.sgul.ac.uk/images/docs/idcp%20pdfs/National%20programme%20on%20substance%20abuse%20deaths/National_Programme_on_Substance_Abuse_Deaths-Annual_Report_2013_on_Drug-related_Deaths_in_the_UK_January-December_2012_PDF.pdf. Accessed 1 Oct 2015.

  6. 6.

    EMCDDA-Europol 2009. Annual report on the implementation of council decision 2005/387/JHA. http://www.emcdda.europa.eu/html.cfm/index132910EN.html. Accessed 1 Oct 2015.

  7. 7.

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

    CAS  Article  PubMed  Google Scholar 

  8. 8.

    Schifano F, Orsolini L, et al. Novel psychoactive substances of interest for psychiatry. World Psychiatry. 2015;14:15–26.

    Article  PubMed  PubMed Central  Google Scholar 

  9. 9.

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

    CAS  Article  PubMed  Google Scholar 

  10. 10.

    Smith B, Higgins C, Baldacchino A, et al. Substance misuse of gabapentin. Br J Gen Pract. 2012;62:406–7.

    Article  PubMed  PubMed Central  Google Scholar 

  11. 11.

    Sweet AD. Pregabalin abuse and the risks associated for patients with a previous history of substance misuse. J Addict Res Ther. 2013;4:e116.

    Google Scholar 

  12. 12.

    Millar, et al. Lyrica nights—recreational pregabalin abuse in an urban emergency department. Emerg Med J. 2013;30:874.

    Article  Google Scholar 

  13. 13.

    Kapil V, Green JL, LeLait MC, et al. Misuse of the γ-aminobutyric acid analogues baclofen, gabapentin and pregabalin in the UK. Br J Clin Pharmacol. 2014;78:190–1.

    CAS  Article  PubMed  Google Scholar 

  14. 14.

    Schifano F, D’Offizi S, Piccione M, 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 

  15. 15.

    Toth C. Drug safety evaluation of pregabalin. Expert Opin Drug Saf. 2012;11:487–502.

    CAS  Article  PubMed  Google Scholar 

  16. 16.

    European Medicines Agency. European public assessment report (EPAR) for Lyrica-Pregabalin; 2010. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Summary_for_the_public/human/000546/WC500046603.pdf. Accessed 16 Sep 2015.

  17. 17.

    Food and Drug Administration. Lyrica (pregabalin) prescribing information; 2009. http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/021446s013s014lbl.pdf. Accessed 1 Dec 2015.

  18. 18.

    Oulis P, Konstantakopoulos G. Efficacy and safety of pregabalin in the treatment of alcohol and benzodiazepine dependence. Expert Opin Investig Drugs. 2012;21:1019–29.

    CAS  Article  PubMed  Google Scholar 

  19. 19.

    Drug Enforcement Administration. Drug scheduling, 2015. http://www.dea.gov/druginfo/ds.shtml. Accessed 16 Sep 2015.

  20. 20.

    MHRA. Drug analysis prints, 2015. http://www.mhra.gov.uk/drug-analysis-prints. Accessed 1 Dec 2015.

  21. 21.

    Caster O, Edwards I, Noren G, Lindquist M. Earlier discovery of pregabalin’s dependence potential might have been possible. Eur J Clin Pharmacol. 2011;67:319–20.

    Article  PubMed  Google Scholar 

  22. 22.

    Schwan S, Sundstrom A, Stjernberg E, et al. A signal for an abuse liability for pregabalin-results from the Swedish spontaneous drug reaction reporting system. EurJ Clin Psychopharmacol. 2010;66:947–53.

    Google Scholar 

  23. 23.

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

    Article  PubMed  Google Scholar 

  24. 24.

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

    Article  PubMed  Google Scholar 

  25. 25.

    Yargic I, Alyanak Ozdemiroglu F. Pregabalin abuse: case report. Klinik Psikofarmakol Bülteni. 2011;21:64–6.

    Article  Google Scholar 

  26. 26.

    Kriikku, et al. Pregabalin serum levels in apprehended drivers. Forensic Sci Int. 2014;243:112–6.

    CAS  Article  PubMed  Google Scholar 

  27. 27.

    Chalabianloo F, Schiott J. Pregabalin and abuse potential [review] [in Norwegian]. Tidsskr Nor Laegeforen. 2009;129:186–7.

    Article  PubMed  Google Scholar 

  28. 28.

    Aldemir E, Altıntoprak AE, Coşkunol H. Pregabalin dependence: a case report. Turk Psikiyatri Derg. 2015;26:217–20.

    PubMed  Google Scholar 

  29. 29.

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

    Article  PubMed  Google Scholar 

  30. 30.

    Gahr M, Franke B, Freudenmann RW, et al. Concerns about pregabalin: further experience with its potential of causing addictive behaviours. J Addict Med. 2013;7:147–9.

    CAS  Article  PubMed  Google Scholar 

  31. 31.

    Grosshans M, Mutschler J, Hermann D, et al. Pregabalin abuse, dependence, and withdrawal: a case report. Am J Psychiatry. 2010;167:869.

    Article  PubMed  Google Scholar 

  32. 32.

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

    Article  PubMed  Google Scholar 

  33. 33.

    Skopp G, Zimmer G. Pregabalin: a drug with abuse potential? [Article in German]. Arch Kriminol. 2012;229:44–54.

    PubMed  Google Scholar 

  34. 34.

    Kalso E, Aldington DJ, Moore RA. Drugs for neuropathic pain. BMJ. 2013;347:f7339.

    Article  PubMed  Google Scholar 

  35. 35.

    Howland RH. Gabapentin for substance use disorders: is it safe and appropriate? J Psychosoc Nurs Ment Health Serv. 2014;6:1–4.

    Google Scholar 

  36. 36.

    Mobasher M, Ziaaddini H, Sabzvari F, Sadeghipour S. The effect of gabapentin on withdrawal syndrome, psychiatric disorders and electroencephalogram of opium addicts during the detoxification period. Iran J Pharm Res. 2010;4:215–23.

    Google Scholar 

  37. 37.

    Sanders NC, Manino MJ, Gentry WB, et al. Randomized, placebo-controlled pilot trial of gabapentin during an outpatient, buprenorphine-assisted detoxification procedure. Exp Clin Psychopharmacol. 2013;21:294–302.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  38. 38.

    Ziaaddini H, Ziaaddini A, Asghari N, et al. Trial of tramadol plus gabapentin for opioid detoxification. Iran Red Crescent Med J. 2015;17:e18202.

    PubMed  Google Scholar 

  39. 39.

    Howland RH. Gabapentin: can it be misused? J Psychosoc Nurs Ment Health Serv. 2014;52:12–5.

    Article  PubMed  Google Scholar 

  40. 40.

    Markowitz JS, Finkenbine R, Myrick H, et al. Gabapentin abuse in a cocaine user: implications for treatment? J Clin Psychopharmacol. 1997;17:423–4.

    CAS  Article  PubMed  Google Scholar 

  41. 41.

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

    Article  PubMed  Google Scholar 

  42. 42.

    MHRA 2015. Drug analysis print; gabapentin. http://www.mhra.gov.uk/home/groups/public/documents/sentineldocuments/dap_8473480656172106.pdf. Accessed 14 May 2016.

  43. 43.

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

    Article  PubMed  Google Scholar 

  44. 44.

    Frampton JE. Pregabalin: a review of its use in adults with generalized anxiety disorder. CNS Drugs. 2014;28:835–54.

    CAS  Article  PubMed  Google Scholar 

  45. 45.

    Badgaiyan RD. A novel perspective on dopaminergic processing of human addiction. J Alcohol Drug Depend. 2013;1.

  46. 46.

    Nagakura Y, Oe T, Aoki T, Matsuoka N. Biogenic amine depletion causes chronic muscular pain and tactile allodynia accompanied by depression: a putative animal model of fibromyalgia. Pain. 2009;146:26–33.

    CAS  Article  PubMed  Google Scholar 

  47. 47.

    Brawek B, Loffler M, Dooley DJ, et al. Differential modulation of K(+)-evoked (3)H-neurotransmitter release from human neocortex by gabapentin and pregabalin. Naunyn Schmiedebergs Arch Pharmacol. 2008;376:301–7.

    CAS  Article  PubMed  Google Scholar 

  48. 48.

    Bockbrader HN, Wesche D, Miller R, et al. A comparison of the pharmacokinetics and pharmacodynamics of pregabalin and gabapentin. Clin Pharmacokinet. 2010;49:661–9.

    CAS  Article  PubMed  Google Scholar 

  49. 49.

    EudraVigilance. European Medicines Agency, 2015. https://eudravigilance.ema.europa.eu/human/index.asp. Accessed 1 Oct 2015.

  50. 50.

    Gov.uk. Countries in the EU and EEA. https://www.gov.uk/eu-eea. Accessed 5 Mar 2016.

  51. 51.

    Heads of Medicines Agency (HMA) and European Medicines Agency (EMA). Guideline on good pharmacovigilance practices (GVP). Module VI: management and reporting of adverse reactions to medicinal products 2014. http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2014/09/WC500172402.pdf. Accessed 1 Dec 2015.

  52. 52.

    Medical Dictionary for Adverse Drug Reactions. MedDRA Version 18.0 English March 2015. http://www.meddra.org/how-to-use/support-documentation/english. Accessed 5 Nov 2015.

  53. 53.

    MedDRA Term Selection: points to consider. Release 4.9 Based on MedDRA Version 18.0 March 2015. http://www.meddra.org/how-to-use/support-documentation/english. Accessed 23 Mar 2016.

  54. 54.

    WHO Expert Committee on Addiction-Producing Drugs. Thirteenth report of the WHO Expert Committee: WHO Technical Report Series, No. 273. Geneva: World Health Organization, 1964.

  55. 55.

    European Medicines Agency. Guideline on the use of statistical signal detection methods in the EudraVigilance data analysis system, 2008. http://www.ema.europa.eu/docs/en_GB/document_library/Regulatory_and_procedural_guideline/2009/11/WC500011434.pdf. Accessed 9 Mar 2016.

  56. 56.

    WHO. The WHO Programme for International Drug Monitoring. http://www.who.int/medicines/areas/quality_safety/safety_efficacy/National_PV_Centres_Map/en/. Accessed 27 Nov 2015.

  57. 57.

    Felicetti P, Trotta F, Bonetto C, et al; Brighton Collaboration Vasculitis Working Group. Spontaneous reports of vasculitis as an adverse event following immunization: a descriptive analysis across three international databases. Vaccine. 2015. doi:10.1016/j.vaccine.2015.09.027.

  58. 58.

    Gahr M, Freudenmann RW, Hiemke C, et al. Pregabalin abuse and dependence in Germany: results from a database query. Eur J Clin Pharmacol. 2013;63:1335–42.

    Article  Google Scholar 

  59. 59.

    Lowry F. Gabapentin new drug of abuse? Medscape Medical News; December 11, 2015. http://www.medscape.com/viewarticle/855819. Accessed 16 Dec 2015.

  60. 60.

    Nichter B, Chassin L. Separate dimensions of anxiety differentially predict alcohol use among male juvenile offenders. Addict Behav. 2015;50:144–8.

    Article  PubMed  Google Scholar 

  61. 61.

    Foster DW, Buckner JD, Schmidt NB, Zvolensky MJ. Multisubstance use among treatment-seeking smokers: synergistic effects of coping motives for cannabis and alcohol use and social anxiety/depressive symptoms. Subst Use Misuse. 2016;51:165–78.

    Article  PubMed  Google Scholar 

  62. 62.

    Nielsen M, Hansen EH, Gøtzsche PC. Dependence and withdrawal reactions to benzodiazepines and selective serotonin reuptake inhibitors. How did the health authorities react? Int J Risk Saf Med. 2013;25:155–68.

    PubMed  Google Scholar 

  63. 63.

    Fernández-Suárez E, Villa-Estébanez R, Garcia-Martinez A, et al. Prevalence, type of epilepsy and use of antiepileptic drugs in primary care. Rev Neurol. 2015;60:535–42.

    PubMed  Google Scholar 

  64. 64.

    Schiltenwolf M, Pogatzki-Zahn EM. Pain medicine from intercultural and gender-related perspectives. Schmerz. 2015;29:569–75.

    CAS  Article  PubMed  Google Scholar 

  65. 65.

    O’Donnell S, Vanderloo S, McRae L, et al. Comparison of the estimated prevalence of mood and/or anxiety disorders in Canada between self-report and administrative data. Epidemiol Psychiatr Sci. 2015;17:1–10.

    Google Scholar 

  66. 66.

    Lourenço S, Costa L, Rodrigues AM, et al. Gender and psychosocial context as determinants of fibromyalgia symptoms (fibromyalgia research criteria) in young adults from the general population. Rheumatol (Oxford). 2015;54:1806–15.

    Article  Google Scholar 

  67. 67.

    Szentkiralyi A, Fendrich K, Hoffmann W, et al. Socio-economic risk factors for incident restless legs syndrome in the general population. J Sleep Res. 2012;21:561–8.

    Article  PubMed  Google Scholar 

  68. 68.

    Finocchi C, Strada L. Sex-related differences in migraine. Neurol Sci. 2014;35(Suppl 1):207–13.

    Article  PubMed  Google Scholar 

  69. 69.

    Ojanperä I, Kriikku P, Vuori E. Fatal toxicity index of medicinal drugs based on a comprehensive toxicology database. Int J Legal Med. 2016. [Epub ahead of print].

  70. 70.

    Zand L, McKian KP, Qian Q. Gabapentin toxicity in patients with chronic kidney disease: a preventable cause of morbidity. Am J Med. 2010;123:367–73.

    CAS  Article  PubMed  Google Scholar 

  71. 71.

    Wills B, Reynolds P, Chu E, et al. Clinical outcomes in newer anticonvulsant overdose: a poison center observational study. J Med Toxicol. 2014;10:254–60.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  72. 72.

    Hakkinen M, Vuori E, Kalso E, et al. Profiles of pregabalin and gabapentin abuse by postmortem toxicology. Forensic Sci Int. 2014;241:1–6.

    CAS  Article  PubMed  Google Scholar 

  73. 73.

    Jones CM, Mack KA, Paulozzi LJ. Pharmaceutical overdose deaths, United States, 2010. JAMA. 2013;309:657–9.

    CAS  Article  PubMed  Google Scholar 

  74. 74.

    Pitkala KH, Juola AL, Hosia H, et al. Eight-year trends in the use of opioids, other analgesics, and psychotropic medications among institutionalized older people in Finland. J Am Med Dir Assoc. 2015;16:973–8.

    Article  PubMed  Google Scholar 

  75. 75.

    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;20:115–8.

    Article  PubMed  Google Scholar 

  76. 76.

    Loftus H, Wright A. Potential misuse of pregabalin and gabapentin. BMJ. 2014;348:g1290.

    Article  PubMed  Google Scholar 

  77. 77.

    Wilens T, Zulauf C, Ryland D, et al. Prescription medication misuse among opioid dependent patients seeking inpatient detoxification. Am J Addict. 2015;24:173–7.

    Article  PubMed  Google Scholar 

  78. 78.

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

    Article  PubMed  Google Scholar 

  79. 79.

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

    CAS  Article  PubMed  Google Scholar 

  80. 80.

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

    Article  PubMed  PubMed Central  Google Scholar 

Download references


We acknowledge the support offered by the EMA in providing access to the EV database. The views expressed here are those of the authors and do not necessarily reflect the EMA officers’ views.

Author information



Corresponding author

Correspondence to Stefania Chiappini.

Ethics declarations


In contributing to this paper, FS was supported in part by grants of the European Commission (Drug Prevention and Information Programme 2014–16, contract no. JUST/2013/DPIP/AG/4823, EU-MADNESS project). Further financial support was provided to FS by the EU Commission-targeted call on cross border law enforcement cooperation in the field of drug trafficking, DG Justice/DG Migrations and Home Affairs (JUST/2013/ISEC/DRUGS/AG/6429) Project EPS/NPS (Enhancing Police Skills concerning Novel Psychoactive Substances).

Conflict of interest

Prof. Schifano and Dr. Chiappini report no conflicts of interest with respect to the content of this manuscript; however, Prof. Schifano is a member of the EMA Psychiatry Advisory Board.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Chiappini, S., Schifano, F. A Decade of Gabapentinoid Misuse: An Analysis of the European Medicines Agency’s ‘Suspected Adverse Drug Reactions’ Database. CNS Drugs 30, 647–654 (2016). https://doi.org/10.1007/s40263-016-0359-y

Download citation


  • Gabapentin
  • Generalize Anxiety Disorder
  • Pregabalin
  • European Medicine Agency
  • Substance Misuse