Prevalence trends and individual patterns of antiepileptic drug use in pregnancy 2006-2016: A study in the five Nordic countries, United States, and Australia.

PURPOSE To describe recent international trends in antiepileptic drug (AED) use during pregnancy and individual patterns of use including discontinuation and switching. METHODS We studied pregnancies from 2006 to 2016 within linked population-based registers for births and dispensed prescription drugs from Denmark, Finland, Iceland, Norway, Sweden, and New South Wales, Australia and claims data for public and private insurance enrollees in the United States. We examined the prevalence of AED use: the proportion of pregnancies with ≥1 prescription filled from 3 months before pregnancy until birth, and individual patterns of use by trimester. RESULTS Prevalence of AED use in almost five million pregnancies was 15.3 per 1000 (n = 75 249) and varied from 6.4 in Sweden to 34.5 per 1000 in the publicly-insured US population. AED use increased in all countries in 2006-2012 ranging from an increase of 22% in Australia to 104% in Sweden, and continued to rise or stabilized in the countries in which more recent data were available. Lamotrigine, clonazepam, and valproate were the most commonly used AEDs in the Nordic countries, United States, and Australia, respectively. Among AED users, 31% only filled a prescription in the 3 months before pregnancy. Most filled a prescription in the first trimester (59%) but few filled prescriptions in every trimester (22%). CONCLUSIONS Use of AEDs in pregnancy rose from 2006 to 2016. Trends and patterns of use of valproate and lamotrigine reflected the safety data available during this period. Many women discontinued AEDs during pregnancy while some switched to another AED.

[1]  S. Hernández-Díaz,et al.  Identifying pregnancies in insurance claims data: Methods and application to retinoid teratogenic surveillance , 2019, Pharmacoepidemiology and drug safety.

[2]  B. Landon,et al.  Patterns in Outpatient Benzodiazepine Prescribing in the United States , 2019, JAMA network open.

[3]  P. Damkier,et al.  Patterns and predictors for prescription of psychotropics and mood‐stabilizing antiepileptics during pregnancy in Denmark 2000–2016 , 2018, British journal of clinical pharmacology.

[4]  Verinder Sharma,et al.  Weighing the Risks: the Management of Bipolar Disorder During Pregnancy , 2018, Current Psychiatry Reports.

[5]  Duong Thuy Tran,et al.  Data cleaning and management protocols for linked perinatal research data: a good practice example from the Smoking MUMS (Maternal Use of Medications and Safety) Study , 2017, BMC Medical Research Methodology.

[6]  S. Hernández-Díaz,et al.  Antipsychotic Medication Use Among Publicly Insured Pregnant Women in the United States. , 2017, Psychiatric services.

[7]  A. Tricco,et al.  Comparative safety of anti-epileptic drugs during pregnancy: a systematic review and network meta-analysis of congenital malformations and prenatal outcomes , 2017, BMC Medicine.

[8]  J. Clayton-Smith,et al.  Monotherapy treatment of epilepsy in pregnancy: congenital malformation outcomes in the child. , 2016, The Cochrane database of systematic reviews.

[9]  M. García-Fiñana,et al.  Cognition in school-age children exposed to levetiracetam, topiramate, or sodium valproate , 2016, Neurology.

[10]  N. Freemantle,et al.  Risks and benefits of psychotropic medication in pregnancy: cohort studies based on UK electronic primary care health records. , 2016, Health technology assessment.

[11]  M. Nørgaard,et al.  Use of SSRI and SNRI Antidepressants during Pregnancy: A Population-Based Study from Denmark, Iceland, Norway and Sweden , 2015, PloS one.

[12]  L. Jong‐van den Berg,et al.  Antiepileptic drug prescribing before, during and after pregnancy: a study in seven European regions , 2015, Pharmacoepidemiology and drug safety.

[13]  J. Hallas,et al.  Primary non-adherence in general practice: a Danish register study , 2014, European Journal of Clinical Pharmacology.

[14]  R. Shelton,et al.  Increasing use of atypical antipsychotics and anticonvulsants during pregnancy , 2013, Pharmacoepidemiology and drug safety.

[15]  Mary K. Kowal,et al.  Harnessing the Medicaid Analytic eXtract (MAX) to Evaluate Medications in Pregnancy: Design Considerations , 2013, PloS one.

[16]  Mogens Vestergaard,et al.  Prenatal valproate exposure and risk of autism spectrum disorders and childhood autism. , 2013, JAMA.

[17]  I. McGregor,et al.  Trends in the utilisation of psychotropic medications in Australia from 2000 to 2011 , 2013, The Australian and New Zealand journal of psychiatry.

[18]  M. Bialer Why are antiepileptic drugs used for nonepileptic conditions? , 2012, Epilepsia.

[19]  R. Davis,et al.  Trends in the use of antiepileptic drugs among pregnant women in the US, 2001-2007: a medication exposure in pregnancy risk evaluation program study. , 2012, Paediatric and perinatal epidemiology.

[20]  W. Hauser,et al.  Comparative safety of antiepileptic drugs during pregnancy , 2012, Neurology.

[21]  T. O'Brien,et al.  Changing patterns of antiepileptic drug use in pregnant Australian women , 2010, Acta neurologica Scandinavica.

[22]  C. Besta,et al.  Utilization of antiepileptic drugs during pregnancy: comparative patterns in 38 countries based on data from the EURAP registry. , 2009, Epilepsia.

[23]  R. Baldessarini,et al.  Risk of recurrence in women with bipolar disorder during pregnancy: prospective study of mood stabilizer discontinuation. , 2007, The American journal of psychiatry.

[24]  P. Lindsay Epilepsy in pregnancy. , 1990, Nursing times.