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Signal of Miscarriage with Aripiprazole: A Disproportionality Analysis of the Japanese Adverse Drug Event Report Database

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Abstract

Introduction

With recent advances in medicines, many patients with schizophrenia have become able to conceive. One common second-generation antipsychotic given to patients with schizophrenia is aripiprazole. The label information of aripiprazole in Japan states that according to one case report “there is a report of miscarriage in clinical trial”.

Objective

The aim of this study was to evaluate the relationship between aripiprazole and miscarriage by conducting a disproportionality analysis of an adverse drug event report database.

Methods

We conducted a disproportionality analysis of second-generation antipsychotic exposure during pregnancy using the Japanese Adverse Drug Event Report database, which is a spontaneous reporting database in Japan. We investigated aripiprazole and other approved second-generation antipsychotics in Japan. In accordance with the previous report, we created a data set for analysis consisting of pregnancy-related reports.

Results

A potential signal for miscarriage was detected for aripiprazole [proportional reporting ratio: 2.39, χ 2: 13.77, reporting odds ratio (95% confidence interval): 2.76 (1.62–4.69); n = 18]. In contrast, no potential signal for miscarriage was detected for other second-generation antipsychotics.

Conclusion

Through our analysis of the Japanese Adverse Drug Event Report database, we found a potential signal for miscarriage for aripiprazole. Safety information on the use of aripiprazole during pregnancy is very limited. Therefore, we suggest that the potential signal detected in our analysis be explored further.

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References

  1. Robinson GE. Treatment of schizophrenia in pregnancy and postpartum. J Popul Ther Clin Pharmacol. 2012;19:e380–6.

    PubMed  Google Scholar 

  2. Habermann F, Fritzsche J, Fuhlbruck F, Wacker E, Allignol A, Weber-Schoendorfer C, Meister R, Schaefer C. Atypical antipsychotic drugs and pregnancy outcome: a prospective, cohort study. J Clin Psychopharmacol. 2013;33:453–62.

    Article  CAS  PubMed  Google Scholar 

  3. Kulkarni J, Worsley R, Gilbert H, Gavrilidis E, Van Rheenen TE, Wang W, McCauley K, Fitzgerald P. A prospective cohort study of antipsychotic medications in pregnancy: the first 147 pregnancies and 100 one-year-old babies. PLoS One. 2014;9:e94788.

    Article  PubMed  PubMed Central  Google Scholar 

  4. McKenna K, Koren G, Tetelbaum M, Wilton L, Shakir S, Diav-Citrin O, Levinson A, Zipursky RB, Einarson A. Pregnancy outcome of women using atypical antipsychotic drugs: a prospective comparative study. J Clin Psychiatry. 2005;66:444–9 (quiz 546).

    Article  CAS  PubMed  Google Scholar 

  5. Cohen LS, Viguera AC, McInerney KA, Freeman MP, Sosinsky AZ, Moustafa D, Marfurt SP, Kwiatkowski MA, Murphy SK, Farrell AM, Chitayat D, Hernández-Díaz S. Reproductive safety of second-generation antipsychotics: current data from the Massachusetts General Hospital National Pregnancy Registry for atypical antipsychotics. Am J Psychiatry. 2016;173:263–70.

    Article  PubMed  Google Scholar 

  6. Huybrechts KF, Hernández-Díaz S, Patorno E, Desai RJ, Mogun H, Dejene SZ, Cohen JM, Panchaud A, Cohen L, Bateman BT. Antipsychotic use in pregnancy and the risk for congenital malformations. JAMA Psychiatry. 2016;73:938–46.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Reis M, Källén B. Maternal use of antipsychotics in early pregnancy and delivery outcome. J Clin Psychopharmacol. 2008;28:279–88.

    Article  CAS  PubMed  Google Scholar 

  8. Yamane R, Hayashi M, Tanaka M, Hishinuma K, Ogawa K, Yokoo I, Kitagawa H. Survey regarding pregnant women receiving novel antipsychotic agents. Iyakuhin Johogaku. 2009;11:35–8.

    Google Scholar 

  9. Gentile S. A safety evaluation of aripiprazole for treating schizophrenia during pregnancy and puerperium. Expert Opin Drug Saf. 2014;13:1733–42.

    Article  CAS  PubMed  Google Scholar 

  10. Windhager E, Kim SW, Saria A, Zauner K, Amminger PG, Klier CM. Perinatal use of aripiprazole: plasma levels, placental transfer, and child outcome in 3 new cases. J Clin Psychopharmacol. 2014;34:637–41.

    Article  CAS  PubMed  Google Scholar 

  11. Gold KJ, Sen A, Hayward RA. Marriage and cohabitation outcomes after pregnancy loss. Pediatrics. 2010;125:e1202–7.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Turner MA, Catapano M, Hirschfeld S, Giaquinto C. Paediatric drug development: the impact of evolving regulations. Adv Drug Deliv Rev. 2014;73:2–13.

    Article  CAS  PubMed  Google Scholar 

  13. de Bie S, Ferrajolo C, Straus SM, Verhamme KM, Bonhoeffer J, Wong IC, Sturkenboom MC. Pediatric drug safety surveillance in FDA-AERS: a description of adverse events from GRiP project. PLoS One. 2015;10:e0130399.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Carter JD, Ladhani A, Ricca LR, Valeriano J, Vasey FB. A safety assessment of tumor necrosis factor antagonists during pregnancy: a review of the Food and Drug Administration database. J Rheumatol. 2009;36:635–41.

    Article  PubMed  Google Scholar 

  15. Deepak P, Stobaugh DJ. Maternal and foetal adverse events with tumour necrosis factor-alpha inhibitors in inflammatory bowel disease. Aliment Pharmacol Ther. 2014;40:1035–43.

    Article  CAS  PubMed  Google Scholar 

  16. Nomura K, Takahashi K, Hinomura Y, Kawaguchi G, Matsushita Y, Marui H, Anzai T, Hashiguchi M, Mochizuki M. Effect of database profile variation on drug safety assessment: an analysis of spontaneous adverse event reports of Japanese cases. Drug Des Devel Ther. 2015;9:3031–41.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Sakai T, Ohtsu F, Sekiya Y, Mori C, Sakata H, Goto N. Methodology for estimating the risk of adverse drug reactions in pregnant women: analysis of the Japanese Adverse Drug Event Report database. Yakugaku Zasshi. 2016;136:499–505.

    Article  CAS  PubMed  Google Scholar 

  18. Bellet F, Beyens MN, Bernard N, Beghin D, Elefant E, Vial T. Exposure to aripiprazole during embryogenesis: a prospective multicenter cohort study. Pharmacoepidemiol Drug Saf. 2015;24:368–80.

    Article  CAS  PubMed  Google Scholar 

  19. Kawaguchi R, Ozawa M, Ohta I, Suzuki M, Hayakawa S, Yamamoto T, Tanaka T. Prolactin (PRL) up-regulates indoleamine 2,3-dioxygenase (IDO) expression in CD14+ cells. Jpn J Clin Immunol. 2015;28:407–12.

    Article  Google Scholar 

  20. Sogawa R, Shimomura Y, Minami C, Maruo J, Kunitake Y, Mizoguchi Y, Kawashima T, Monji A, Hara H. Aripiprazole-associated hypoprolactinemia in the clinical setting. J Clin Psychopharmacol. 2016;36:385–7.

    Article  CAS  PubMed  Google Scholar 

  21. Propst AJ, Jarvis GE, Margolese HC. Aripiprazole-induced hypoprolactinemia in an adult male with first-episode psychosis. Clin Schizophr Relat Psychoses. 2016;9:173–6.

    Article  PubMed  Google Scholar 

  22. Toh S, Li Q, Cheetham TC, Cooper WO, Davis RL, Dublin S, Hammad TA, Li DK, Pawloski PA, Pinheiro SP, Raebel MA, Scott PE, Smith DH, Bobo WV, Lawrence JM, Dashevsky I, Haffenreffer K, Avalos LA, Andrade SE. Prevalence and trends in the use of antipsychotic medications during pregnancy in the US, 2001–2007: a population-based study of 585,615 deliveries. Arch Womens Ment Health. 2013;16:149–57.

    Article  PubMed  PubMed Central  Google Scholar 

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Correspondence to Takamasa Sakai.

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Funding

No specific funding was received for the preparation of this study.

Conflict of interest

Takamasa Sakai, Fumiko Ohtsu, Chiyo Mori, Kouichi Tanabe and Nobuyuki Goto have no conflicts of interest directly relevant to the content of this study.

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Sakai, T., Ohtsu, F., Mori, C. et al. Signal of Miscarriage with Aripiprazole: A Disproportionality Analysis of the Japanese Adverse Drug Event Report Database. Drug Saf 40, 1141–1146 (2017). https://doi.org/10.1007/s40264-017-0560-z

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  • DOI: https://doi.org/10.1007/s40264-017-0560-z

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