Continuation of Atypical Antipsychotic Medication During Early Pregnancy and the Risk of Gestational Diabetes
Publication: American Journal of Psychiatry
Abstract
Objective:
Some atypical antipsychotics are associated with metabolic side effects, which are risk factors for gestational diabetes. The authors examined the risk of developing gestational diabetes associated with the continuation of treatment with aripiprazole, ziprasidone, quetiapine, risperidone, and olanzapine during pregnancy compared with discontinuation of these antipsychotic drugs.
Method:
Nondiabetic pregnant women who were linked to a live-born infant and enrolled in Medicaid (2000–2010) and who received one or more prescriptions dispensed for an antipsychotic drug during the 3 months before pregnancy were included in the analyses. Among 1,543,334 pregnancies, some expectant mothers at baseline were receiving treatment with aripiprazole (N=1,924), ziprasidone (N=673), quetiapine (N=4,533), risperidone (N=1,824), or olanzapine (N=1,425). For each antipsychotic drug, women with two or more dispensings (“continuers”) were compared with women with no dispensings (“discontinuers”) during the first half of pregnancy. A generalized linear model and propensity-score stratification were used to obtain absolute and relative risks of developing gestational diabetes, with adjustment for confounders.
Results:
Women who continued antipsychotic treatment during pregnancy generally had higher comorbidity and longer baseline antipsychotic use. The crude risk of developing gestational diabetes among continuers compared with discontinuers, respectively, was 4.8% and 4.5% for aripiprazole, 4.2% and 3.8% for ziprasidone, 7.1% and 4.1% for quetiapine, 6.4% and 4.1% for risperidone, and 12.0% and 4.7% for olanzapine. The adjusted relative risks were 0.82 (95% CI=0.50–1.33) for aripiprazole, 0.76 (95% CI=0.29–2.00) for ziprasidone, 1.28 (95% CI=1.01–1.62) for quetiapine, 1.09 (95% CI=0.70–1.70) for risperidone, and 1.61 (95% CI=1.13–2.29) for olanzapine.
Conclusions:
Compared with women who discontinued use of an atypical antipsychotic medication before the start of pregnancy, women who continued treatment with olanzapine or quetiapine had an increased risk of gestational diabetes that may be explained by the metabolic effects associated with these two drugs.
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History
Received: 6 April 2017
Revision received: 25 September 2017
Revision received: 13 November 2017
Revision received: 19 December 2017
Revision received: 15 January 2018
Accepted: 22 January 2018
Published online: 7 May 2018
Published in print: June 01, 2018
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Funding Information
National Institute of Mental Health10.13039/100000025: K01MH099141, R01MH100216
Supported by a grant from NIMH (grant R01 MH100216).Dr. Park has served as a consultant for Optum. Dr. Hernandez-Diaz has served as a consultant for Boehringer-Ingelheim and UCB; she has served as the epidemiologist for the North American Antiepileptic Drugs Pregnancy Registry (which is supported by funds provided by AbbVie, Concordia, Janssen, Novartis, Pfizer, Sunovion, and UCB Pharmaceuticals) and as an adviser to the Massachusetts General Hospital National Pregnancy Registry for Atypical Antipsychotics (supported by funds provided by Apotex, Aurobindo Pharma, Dr. Reddy’s Labs, GlaxoSmithKline, Sandoz, and Teva); and she has served as an investigator for grants to the Brigham and Women’s Hospital from Lilly and Pfizer (unrelated to this study). Dr. Jacqueline M. Cohen has received salary support from a research grant to the Harvard T. H. Chan School of Public Health from GlaxoSmithKline (unrelated to this study). Dr. Desai has served as the principal investigator for a research grant from Merck to Brigham and Women’s Hospital (unrelated to this study). Dr. Patorno has received grant support from the National Institute on Aging (grant K08AG055670); she has served as an investigator for investigator-initiated grants to Brigham and Women’s Hospital from Boehringer Ingelheim (grant K08AG055670) and GlaxoSmithKline (unrelated to this study). Dr. Glynn has received research support from grants to Brigham and Women’s Hospital from Kowa, Novartis, and Pfizer (unrelated to this study). Dr. Lee S. Cohen has received research grant support from Alkermes Biopharmaceuticals, AstraZeneca Pharmaceuticals, Forest/Actavis Pharmaceuticals, Ortho-McNeil Janssen Pharmaceuticals, Otsuka Pharmaceuticals, and Sunovion Pharmaceuticals; he has received other research support from the Brain and Behavior Research Foundation, JayMac Pharmaceuticals, the National Institute on Aging, NIH, NIMH, SAGE Therapeutics, and Takeda/Lundbeck Pharmaceuticals; and he has served as an adviser to or consultant for JDS Therapeutics (unrelated to this study). All other authors report no financial relationships with commercial interests.Metrics & Citations
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