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Signal of Gastrointestinal Congenital Malformations with Antipsychotics After Minimising Competition Bias: A Disproportionality Analysis Using Data from Vigibase®

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Abstract

Introduction

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.

Method

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.

Results

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.

Conclusion

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.

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Acknowledgments

The authors would like to thank the UMC, which provided and gave permission to use the data analysed in the present study.

The authors are indebted to the National Pharmacovigilance Centres that contributed data. The opinions and conclusions in this study are not necessarily those of the various centres or the WHO.

The authors gratefully acknowledge Mrs Christine Damase-Michel and Mrs Isabelle Lacroix for their advice and corrections. The authors also thank Mr Ray Cooke for revising the English.

Authors’ contributions

François Montastruc, Bernard Bégaud and Antoine Pariente participated in the study design and planning; François Montastruc, Francesco Salvo, Mickaël Arnaud, Bernard Bégaud and Antoine Pariente took part in the acquisition, analysis and interpretation of the data; François Montastruc, Bernard Bégaud and Antoine Pariente drafted the manuscript; and Francesco Salvo, Mickaël Arnaud, Bernard Bégaud and Antoine Pariente critically revised the manuscript for important intellectual content. All authors approved the final version of the manuscript.

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Authors and Affiliations

  1. INSERM, U1219-Pharmacoepidemiology, Université de Bordeaux, 33000, Bordeaux, France

    François Montastruc, Francesco Salvo, Mickaël Arnaud, Bernard Bégaud & Antoine Pariente

  2. Service de Pharmacologie Médicale et Clinique, Faculté de Médecine, CHU Toulouse, 37 alles Jules Guesde, 31000, Toulouse, France

    François Montastruc

  3. French Regional Pharmacovigilance Centres Network, Bordeaux, France

    François Montastruc, Bernard Bégaud & Antoine Pariente

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  1. François Montastruc
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Correspondence to François Montastruc.

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No specific funding was received for this study.

Conflicts of interest

François Montastruc, Francesco Salvo, Mickaël Arnaud, Bernard Bégaud and Antoine Pariente have no conflicts of interest that are directly relevant to the content of this study.

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Montastruc, F., Salvo, F., Arnaud, M. et al. Signal of Gastrointestinal Congenital Malformations with Antipsychotics After Minimising Competition Bias: A Disproportionality Analysis Using Data from Vigibase® . Drug Saf 39, 689–696 (2016). https://doi.org/10.1007/s40264-016-0413-1

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