Skip to main content
SpringerLink
Log in

Disproportionality Analysis for the Assessment of Abuse and Dependence Potential of Pregabalin in the French Pharmacovigilance Database

  • Original Research Article
  • Published:
Clinical Drug Investigation Aims and scope Submit manuscript

Abstract

Background and Objective

Pregabalin abuse and dependence has been increasingly described; however, it is not described in France. Our study aimed to investigate the abuse and dependence potential of pregabalin by a disproportionality analysis, in the French Pharmacovigilance Database (FPVD), in comparison with amitriptyline and clonazepam.

Methods

We performed a case/noncase study in the FPVD. Between January, 1 2010 and December, 31 2015, we identified cases of abuse and or dependence (excluding isolated withdrawal syndromes) using MedDRA (Medical Dictionary for Regular Activities) terms. Exposure to pregabalin was defined as the mention of pregabalin in the report. Clonazepam was used as positive control and amitriptyline as negative control.

Results

Among the 184,310 reports in the database, 521 were abuse or dependence cases. Exposure to pregabalin was found in eight (1.5 %) of them. We did not find any significant association between exposure to pregabalin and drug abuse or dependence: reporting odds ratio (ROR) = 1.1 95 % confidence interval (CI) (0.6–2.3). ROR for clonazepam was 5.7 95 % CI (3.5–9.2). No case of an amitriptyline-related abuse or dependence was recorded in the FPVD.

Conclusions

The first cases of pregabalin-related abuse or dependence reported in France occurred later than in other European countries, since none had been described before 2010. This analysis in the FPVD did not find a higher proportion of abuse/dependence with pregabalin in comparison with other drugs. Considering evidence of pregabalin abuse worldwide, this analysis underlines the limitations of spontaneous reporting system in the field of addictovigilance.

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. Sills GJ. The mechanisms of action of gabapentin and pregabalin. Curr Opin Pharmacol. 2006;6(1):108–13.

    Article  CAS  PubMed  Google Scholar 

  2. Matsuzawa R, Fujiwara T, Nemoto K, Fukushima T, Yamaguchi S, Akagawa K, et al. Presynaptic inhibitory actions of pregabalin on excitatory transmission in superficial dorsal horn of mouse spinal cord: further characterization of presynaptic mechanisms. Neurosci Lett. 2014;558:186–91.

    Article  CAS  PubMed  Google Scholar 

  3. Lapeyre-Mestre M, Dupui M. Drug abuse monitoring: which pharmacoepidemiological resources at the European level? Thérapie. 2015;70(2):147–65.

    Article  PubMed  Google Scholar 

  4. 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 

  5. 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 

  6. 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 

  7. 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 

  8. European Medicines Agency (EMA). Lyrica Procedural steps taken and scientific information after the authorisation [Internet]. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Procedural_steps_taken_and_scientific_information_after_authorisation/human/000546/WC500046604.pdf. Accessed 12 June 2016.

  9. 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 

  10. 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.

    Article  CAS  PubMed  Google Scholar 

  11. Kapil V, Green JL, Le Lait M-C, 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 

  12. Schjøtt J, Bergman J. Joint medicine-information and pharmacovigilance services could improve detection and communication about drug-safety problems. Drug Healthc Patient Saf. 2014;6:89–92.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Assurance Maladie. ameli.fr - Medic’AM [Internet]. ameli.fr. Available from: http://www.ameli.fr/l-assurance-maladie/statistiques-et-publications/donnees-statistiques/medicament/medic-am/medic-am-2012-2014.php. Accessed 12 June 2016.

  14. Fuzier R, Serres I, Guitton E, Lapeyre-Mestre M, Montastruc JL, French Network of Pharmacovigilance Centres. Adverse drug reactions to gabapentin and pregabalin: a review of the French pharmacovigilance database. Drug Saf. 2013;36(1):55–62.

    Article  CAS  PubMed  Google Scholar 

  15. Arimone Y, Bidault I, Dutertre J-P, Gérardin M, Guy C, Haramburu F, et al. Updating the French method for the causality assessment of adverse drug reactions. Thérapie. 2013;68(2):69–76.

    Article  PubMed  Google Scholar 

  16. European Parliament and Council of Ministers. Directive 2010/84/EU [Internet]. Available from: http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2010:348:0074:0099:EN:PDF. Accessed 12 June 2016.

  17. ANSM: Agence nationale de sécurité du médicament et des produits de santé. Pharmacodépendance (Addictovigilance) [Internet]. Available from: http://ansm.sante.fr/Declarer-un-effet-indesirable/Pharmacodependance-Addictovigilance/Pharmacodependance-Addictovigilance/%28offset%29/0. Accessed 12 June 2016.

  18. Jouanjus E, Lapeyre-Mestre M, Micallef J, French Association of the Regional Abuse and Dependence Monitoring Centres (CEIP-A) Working Group on Cannabis Complications. Cannabis use: signal of increasing risk of serious cardiovascular disorders. J Am Heart Assoc. 2014;3(2):e000638.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Jouanjus E, Gibaja V, Kahn J-P, Haramburu F, Daveluy A. Signal identification in addictovigilance: the functioning of the French system. Thérapie. 2015;70(2):113–31.

    Article  PubMed  Google Scholar 

  20. Bate A, Evans SJW. Quantitative signal detection using spontaneous ADR reporting. Pharmacoepidemiol Drug Saf. 2009;18(6):427–36.

    Article  CAS  PubMed  Google Scholar 

  21. Montastruc J-L, Sommet A, Bagheri H, Lapeyre-Mestre M. Benefits and strengths of the disproportionality analysis for identification of adverse drug reactions in a pharmacovigilance database. Br J Clin Pharmacol. 2011;72(6):905–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Montastruc G, Favreliere S, Sommet A, Pathak A, Lapeyre-Mestre M, Perault-Pochat M-C, et al. Drugs and dilated cardiomyopathies: a case/noncase study in the French PharmacoVigilance Database. Br J Clin Pharmacol. 2010;69(3):287–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Martinez V, Attal N, Bouhassira D, Lantéri-Minet M. Les douleurs neuropathiques chroniques: diagnostic, évaluation et traitement en médecine ambulatoire. Recommandations pour la pratique clinique de la Société française d’étude et de traitement de la douleur. Douleurs Eval Diagn Trait. 2010;11(1):3–21.

    Article  Google Scholar 

  24. Rothman KJ, Lanes S, Sacks ST. The reporting odds ratio and its advantages over the proportional reporting ratio. Pharmacoepidemiol Drug Saf. 2004;13(8):519–23.

    Article  PubMed  Google Scholar 

  25. 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 

  26. Schjerning O, Rosenzweig M, Pottegård A, Damkier P, Nielsen J. Abuse potential of pregabalin: a systematic review. CNS Drugs. 2016;30(1):9–25.

    Article  CAS  PubMed  Google Scholar 

  27. Millar J, Sadasivan S, Weatherup N, Lutton S. Lyrica nights–recreational pregabalin abuse in an Urban Emergency Department. Emerg Med J. 2013;30(10):874.

    Article  Google Scholar 

  28. Baird CRW, 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 

  29. European Medicines Agency (EMA). European Medicines Agency (EMA) Lyrica (pregabalin) Scientific Discussion. [Internet]. Disponible sur: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Scientific_Discussion/human/000546/WC500046600.pdf. Accessed 13 June 2016.

  30. 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 

  31. Bramness JG, Sandvik P, Engeland A, Skurtveit S. Does Pregabalin (Lyrica(®)) help patients reduce their use of benzodiazepines? A comparison with gabapentin using the Norwegian Prescription Database. Basic Clin Pharmacol Toxicol. 2010;107(5):883–6.

    CAS  PubMed  Google Scholar 

  32. Pauly V, Lapeyre-Mestre M, Braunstein D, Rueter M, Thirion X, Jouanjus E, et al. Detection of signals of abuse and dependence applying disproportionality analysis. Eur J Clin Pharmacol. 2015;71(2):229–36.

    Article  CAS  PubMed  Google Scholar 

  33. Beau-Salinas F, Jonville-Béra AP, Cissoko H, Bensouda-Grimaldi L, Autret-Leca E. Drug dependence associated with triptans and ergot derivatives: a case/non-case study. Eur J Clin Pharmacol. 2010;66(4):413–7.

    Article  PubMed  Google Scholar 

  34. Victorri-Vigneau C, Dailly E, Veyrac G, Jolliet P. Evidence of zolpidem abuse and dependence: results of the French Centre for Evaluation and Information on Pharmacodependence (CEIP) network survey. Br J Clin Pharmacol. 2007;64(2):198–209.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Laboratoire Roche®. RIVOTRIL®: Informations importantes sur le bon usage - Réduction du conditionnement des comprimés [Internet]. Available from: http://ansm.sante.fr/S-informer/Informations-de-securite-Lettres-aux-professionnels-de-sante/Informations-importantes-sur-le-bon-usage-du-RIVOTRIL-R-et-sur-la-reduction-du-conditionnement-des-comprimes. Accessed 12 June 2016.

  36. Expériences - Lyrica [Internet]. PsychoActif. 2015 Available from: https://www.psychoactif.org/forum/t13178-p1-Lyrica.html#divx. Accessed 12 June 2016.

  37. Pariente A, Didailler M, Avillach P, Miremont-Salamé G, Fourrier-Reglat A, Haramburu F, et al. A potential competition bias in the detection of safety signals from spontaneous reporting databases. Pharmacoepidemiol Drug Saf. 2010;19(11):1166–71.

    Article  PubMed  Google Scholar 

  38. Driot D, Dupouy J, Palmaro A, Jouanjus E, Lapeyre-Mestre M. Pregabalin abuse in France: resulst of a national retrospective and comparative cohort study. Fundam Clin Pharmacol. 2016;30:40.

    Google Scholar 

Download references

Acknowledgments

We wish to thank the 31 Regional Pharmacovigilance Centres (CRPV, Centres Régionaux de Pharmacovigilance) for providing data, and the French Drug Agency (ANSM, Agence Nationale de Sécurité du Médicament), who own the database, for agreeing for us to explore the FPVD. The results and conclusions reported in this article are exclusively those of the authors and are independent from the ANSM. The authors declare that they have no conflict of interest. This study was not funded.

Contributions of Authors

J-B. Bossard and C. Ponté: acquisition, analysis and interpretation of data, drafting the article and revising it critically for important intellectual content, and final approval of the version to be published. E. Jouanjus and J. Dupouy: conception and design, analysis and interpretation of data, revising the article critically for important intellectual content, and final approval of the version to be published. M. Lapeyre-Mestre: conception and design, interpretation of data, revising the article critically for important intellectual content, and final approval of the version to be published.

Author information

Authors and Affiliations

  1. Equipe de Pharmacoepidemiologie, UMR1027-Université Paul Sabatier Toulouse III, 37 allées Jules Guesde, 31000, Toulouse, France

    Jean-Baptiste Bossard, Julie Dupouy, Maryse Lapeyre-Mestre & Emilie Jouanjus

  2. CEIP-Addictovigilance, Service de Pharmacologie Médicale et Clinique, CHU Toulouse, 37 allées Jules Guesde, 31000, Toulouse, France

    Camille Ponté, Maryse Lapeyre-Mestre & Emilie Jouanjus

  3. Département Universitaire de Médecine Générale, Université Paul Sabatier Toulouse III, Faculté de Médecine, 133, route de Narbonne, Toulouse, 31062, France

    Julie Dupouy

Authors
  1. Jean-Baptiste Bossard
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Camille Ponté
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Julie Dupouy
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Maryse Lapeyre-Mestre
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Emilie Jouanjus
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Emilie Jouanjus.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bossard, JB., Ponté, C., Dupouy, J. et al. Disproportionality Analysis for the Assessment of Abuse and Dependence Potential of Pregabalin in the French Pharmacovigilance Database. Clin Drug Investig 36, 735–742 (2016). https://doi.org/10.1007/s40261-016-0421-z

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40261-016-0421-z

Keywords

Search

Navigation