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The importance of drug–drug interactions as a cause of adverse drug reactions: a pharmacovigilance study of serotoninergic reuptake inhibitors in France

  • Pharmacoepidemiology and Prescription
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European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

To quantify the importance of drug–drug interactions (DDIs) in the occurrence of adverse drug reactions (ADRs) reported with serotoninergic reuptake inhibitors in a pharmacovigilance database.

Methods

All spontaneous reports of ADRs registered in 2008 by the Midi-Pyrénées PharmacoVigilance Centre that contained mention of one of the serotoninergic reuptake inhibitor (SRI) antidepressants marketed in France were reviewed. DDIs were identified according to the French National Drug Formulary (Vidal) and the interaction supplement of the French independent drug bulletin La Revue Prescrire. ADRs explained by DDIs were characterised.

Results

Among the 2,101 spontaneous reports recorded, 177 involved at least one SRI antidepressant. Among the 156 ADRs with at least one theoretical DDI, 41% (95% confidence interval 34–49%) could be explained by a DDI. The most frequent antidepressant involved in DDIs was escitalopram, followed by fluoxetine and citalopram. Among the 65 ADRs related to DDIs, 37 (52.9%) were “serious”, mainly bleedings, confusion and falls, hyponatremia and serotoninergic syndromes. The most frequent drug interactions occurred with psychotropics (antipsychotics, benzodiazepines, among others), followed by antithrombotic agents (antagonists of vitamin K, antiplatelets), diuretics and angiotensin II antagonists. The group with ADRs related to DDIs was older than the group with ADRs not related to DDIs. ADRs were threefold more “serious” in the case of DDIs.

Conclusion

Around 40% of ADRs reported with SRIs were related to DDIs. Most of these occurred after association with psychotropics, antithrombotics, or diuretics, especially in the elderly.

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Authors and Affiliations

  1. Laboratoire de Pharmacologie Médicale et Clinique, UMR-INSERM U1027, Equipe de Pharmacoépidémiologie, Faculté de Médecine , Université de Toulouse, 37 allées Jules-Guesde, 31000, Toulouse, France

    Francois Montastruc, Agnès Sommet, Emmanuelle Bondon-Guitton, Geneviève Durrieu, Haleh Bagheri, Maryse Lapeyre-Mestre & Jean-Louis Montastruc

  2. Service de Pharmacologie Clinique, Centre Midi-Pyrénées de Pharmacovigilance, de Pharmacoépidémiologie et d’Informations sur le Médicament, Centre Hospitalier Universitaire de Toulouse, Toulouse, France

    Francois Montastruc, Agnès Sommet, Emmanuelle Bondon-Guitton, Geneviève Durrieu, Haleh Bagheri, Maryse Lapeyre-Mestre, Laurent Schmitt & Jean-Louis Montastruc

  3. Service Hospitalo-Universitaire de Psychiatrie et Psychologie Médicale, Centre Hospitalier Universitaire, Hôpital Purpan, Faculté de Médecine de l’Université de Toulouse, Toulouse, France

    Francois Montastruc, Eric Bui & Laurent Schmitt

Authors
  1. Francois Montastruc
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  2. Agnès Sommet
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  3. Emmanuelle Bondon-Guitton
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  4. Geneviève Durrieu
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  5. Eric Bui
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  6. Haleh Bagheri
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  7. Maryse Lapeyre-Mestre
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  8. Laurent Schmitt
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  9. Jean-Louis Montastruc
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Corresponding author

Correspondence to Jean-Louis Montastruc.

Additional information

Contributions

F.M. and J-L.M performed the study in the French National PharmacoVigilance database. F.M and A.S analysed the data. J-L.M wrote the manuscript. E.B-G, G.D, H.B reviewed all the reports of ADRs. All of the authors revised the text.

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Montastruc, F., Sommet, A., Bondon-Guitton, E. et al. The importance of drug–drug interactions as a cause of adverse drug reactions: a pharmacovigilance study of serotoninergic reuptake inhibitors in France. Eur J Clin Pharmacol 68, 767–775 (2012). https://doi.org/10.1007/s00228-011-1156-7

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  • DOI: https://doi.org/10.1007/s00228-011-1156-7

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