title: The importance of drug-drug interactions as a cause of adverse drug reactions: a pharmacovigilance study of serotoninergic reuptake inhibitors in France.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors: 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.
authors: Francois
authors: F
authors: Montastruc
authors: Agnès
authors: A
authors: Sommet
authors: Emmanuelle
authors: E
authors: Bondon-Guitton
authors: Geneviève
authors: G
authors: Durrieu
authors: Eric
authors: E
authors: Bui
authors: Haleh
authors: H
authors: Bagheri
authors: Maryse
authors: M
authors: Lapeyre-Mestre
authors: Laurent
authors: L
authors: Schmitt
authors: Jean-Louis
authors: JL
authors: Montastruc
mesh_terms: D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems; D000367:Age Factors; D000928:Antidepressive Agents / Q000009:adverse effects*; D015283:Citalopram / Q000009:adverse effects; D003221:Confusion / Q000139:chemically induced; D004232:Diuretics / Q000009:adverse effects; D004347:Drug Interactions; D005260:Female; D005343:Fibrinolytic Agents / Q000009:adverse effects; D005473:Fluoxetine / Q000009:adverse effects; D005602:France; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D007010:Hyponatremia / Q000139:chemically induced; D008297:Male; D060735:Pharmacovigilance; D011619:Psychotropic Drugs / Q000009:adverse effects*; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects*
chemical_list: D000928:Antidepressive Agents; D015283:Citalopram; D004232:Diuretics; D005343:Fibrinolytic Agents; D005473:Fluoxetine; D011619:Psychotropic Drugs; D017367:Selective Serotonin Reuptake Inhibitors