title: Signal of Gastrointestinal Congenital Malformations with Antipsychotics After Minimising Competition Bias: A Disproportionality Analysis Using Data from Vigibase(®).
abstract: Investigations have highlighted the lack of evidence regarding the likelihood of congenital malformations following exposure to antipsychotic drugs during pregnancy. To gain further knowledge regarding their safety, we evaluated signals of congenital malformations with antipsychotics using VigiBase(®), the World Health Organization (WHO) Global Individual Case Safety Report (ICSR) database.
  
  
  
  A case/non-case study was conducted in VigiBase(®) between 1967 and 2014. Signals of disproportionate reporting (SDRs) were detected using the proportional reporting ratio (PRR), which defines SDRs as drug-report associations with a PRR ≥2, Chi square ≥4, and number of cases ≥3. SDR detection for antipsychotics was performed for congenital malformations after removing all reports related to drug competitors and reports of movement disorders from the database.
  
  
  
  After removing reports related to drug competitors (antiepileptics, antidepressants, antivirals) and movement disorders, three signals were revealed: 'palate disorders congenital' (PRR 2.1, 95 % CI 1.6-2.9, Chi square = 30; n = 41), 'oesophageal disorders congenital' (PRR 2.5, 95 % CI 1.3-4.7, Chi square = 11; n = 10) and 'anorectal disorders congenital' (PRR 3.0, 95 % CI 1.6-5.6, Chi square = 13; n = 11). Among antipsychotics, phenothiazines with a piperazine side-chain, risperidone and aripiprazole appeared to be more suspect.
  
  
  
  Confirming a first signal from spontaneous reporting data, three SDRs for antipsychotics and gastrointestinal congenital abnormalities were unmasked in VigiBase(®). This signal should be further explored by ad hoc pharmacoepidemiologic studies in order to assess whether it is relevant for prescription and public health.
authors.affiliation: INSERM, U1219-Pharmacoepidemiology, Université de Bordeaux, 33000, Bordeaux, France. francois.montastruc@univ-tlse3.fr.|Service de Pharmacologie Médicale et Clinique, Faculté de Médecine, CHU Toulouse, 37 alles Jules Guesde, 31000, Toulouse, France. francois.montastruc@univ-tlse3.fr.|French Regional Pharmacovigilance Centres Network, Bordeaux, France. francois.montastruc@univ-tlse3.fr.
authors.forename: François
authors.initials: F
authors.lastname: Montastruc
authors.affiliation: INSERM, U1219-Pharmacoepidemiology, Université de Bordeaux, 33000, Bordeaux, France.
authors.forename: Francesco
authors.initials: F
authors.lastname: Salvo
authors.affiliation: INSERM, U1219-Pharmacoepidemiology, Université de Bordeaux, 33000, Bordeaux, France.
authors.forename: Mickaël
authors.initials: M
authors.lastname: Arnaud
authors.affiliation: INSERM, U1219-Pharmacoepidemiology, Université de Bordeaux, 33000, Bordeaux, France.|French Regional Pharmacovigilance Centres Network, Bordeaux, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Bégaud
authors.affiliation: INSERM, U1219-Pharmacoepidemiology, Université de Bordeaux, 33000, Bordeaux, France.|French Regional Pharmacovigilance Centres Network, Bordeaux, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Pariente
mesh_terms: D016907:Adverse Drug Reaction Reporting Systems; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D015982:Bias; D016022:Case-Control Studies; D062313:Databases, Pharmaceutical; D004065:Digestive System Abnormalities / Q000139:chemically induced* / Q000453:epidemiology; D006801:Humans; D060735:Pharmacovigilance
chemical_list: D014150:Antipsychotic Agents