Trends in the Use of Antiepileptic Drugs among Pregnant Women in the US, 2001–2007: A Medication Exposure in Pregnancy Risk Evaluation Program Study

Bobo, William V.; Davis, Robert L.; Toh, Sengwee; Li, De-Kun; Andrade, Susan E.; Cheetham, T. Craig; Pawloski, Pamala A.; Dublin, Sascha; Pinheiro, Simone P.; Hammad, Tarek A.; Scott, Pamela E.; Epstein, Richard A.; Arbogast, Patrick G.; Morrow, James; Dudley, Judith A.; Lawrence, Jean M.; Avalos, Lyndsay A.; Cooper, William O.

doi:10.1111/ppe.12004

Cited by 70 publications

(61 citation statements)

References 38 publications

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“…They found that 0.9% received benzodiazepines at any time in pregnancy while 0.2% received valproic acid derivatives. 40 Of those who were dispensed an old anticonvulsant mood stabiliser 4024 out of 9001 (45%) had an indication of psychiatric disorder, while 2115 out of 3515 (60%) of those dispensed new anticonvulsant mood stabilisers had an indication of psychiatric disorder. Only between 21% and 25% had an indication of epilepsy.…”

Section: Psychotropic Medication Prescribed Before During and After mentioning

confidence: 99%

“…7 The utilisation of anticonvulsant mood stabilisers was examined in another US study also based on pharmacy dispensing data from nearly 600,000 pregnancies. 40 This study included benzodiazepines as one of the 'older' anticonvulsant mood stabilisers and the prevalence estimates were primarily driven by the dispensing of these drugs. They found that 0.9% received benzodiazepines at any time in pregnancy while 0.2% received valproic acid derivatives.…”

Section: Psychotropic Medication Prescribed Before During and After mentioning

confidence: 99%

“…One study 37 reported a sharp increase in the use of atypical antipsychotics from 0.33% [95% confidence interval (CI) 0.29% to 0.37%)] in 2001 to 0.82% (95% CI 0.76% to 0.88%) in 2007, while the use of typical antipsychotics remained stable. The other study 40 estimated that in 2001 there were 15.7 women receiving anticonvulsant mood stabilisers per 1000 deliveries in the USA, increasing to 21.9 per 1000 deliveries in 2007. A more recent study 34 based on data from THIN demonstrated that for anticonvulsant mood stabilisers the overall prevalence of prescribing in pregnancy has remained at the same level, between 0.4% and 0.6% between 1994 and 2009; however, the prevalence of prescribing of individual types of anticonvulsants has changed over time with lamotrigine becoming increasingly common.…”

Section: Introductionmentioning

confidence: 99%

“…This has been the subject of a number of recent studies conducted in Europe and North America. [34][35][36][37][38][39][40][41] Epstein et al 39 examined use of psychotropic medication using data from Tennessee Medicaid to conduct a retrospective cohort study of nearly 300,000 women enrolled in the database throughout pregnancy from 1985 to 2005. This study reported significant increases in the use of anticonvulsants among mothers with pain and other psychiatric disorders, but a decrease in the use of lithium and typical antipsychotics.…”

Section: Introductionmentioning

confidence: 99%

“…This study reported significant increases in the use of anticonvulsants among mothers with pain and other psychiatric disorders, but a decrease in the use of lithium and typical antipsychotics. 39 Two studies 37,40 based on pharmacy dispensing data from the USA estimated the prevalence of anticonvulsant mood stabilisers and antipsychotics dispensed during pregnancy over the period 2001-7 from 11 US health plans participating in the Medication Exposure in Pregnancy Risk Evaluation Program involving 585,615 deliveries. One study 37 reported a sharp increase in the use of atypical antipsychotics from 0.33% [95% confidence interval (CI) 0.29% to 0.37%)] in 2001 to 0.82% (95% CI 0.76% to 0.88%) in 2007, while the use of typical antipsychotics remained stable.…”

Section: Introductionmentioning

confidence: 99%

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Risks and benefits of psychotropic medication in pregnancy: cohort studies based on UK electronic primary care health records

Petersen

McCrea

Sammon

et al. 2016

Health Technol Assess

133

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BackgroundAlthough many women treated with psychotropic medication become pregnant, no psychotropic medication has been licensed for use in pregnancy. This leaves women and their health-care professionals in a treatment dilemma, as they need to balance the health of the woman with that of the unborn child. The aim of this project was to investigate the risks and benefits of psychotropic medication in women treated for psychosis who become pregnant.Objective(s)(1) To provide a descriptive account of psychotropic medication prescribed before pregnancy, during pregnancy and up to 15 months after delivery in UK primary care from 1995 to 2012; (2) to identify risk factors predictive of discontinuation and restarting of lithium (multiple manufacturers), anticonvulsant mood stabilisers and antipsychotic medication; (3) to examine the extent to which pregnancy is a determinant for discontinuation of psychotropic medication; (4) to examine prevalence of records suggestive of adverse mental health, deterioration or relapse 18 months before and during pregnancy, and up to 15 months after delivery; and (5) to estimate absolute and relative risks of adverse maternal and child outcomes of psychotropic treatment in pregnancy.DesignRetrospective cohort studies.SettingPrimary care.ParticipantsWomen treated for psychosis who became pregnant, and their children.InterventionsTreatment with antipsychotics, lithium or anticonvulsant mood stabilisers.Main outcome measuresDiscontinuation and restarting of treatment; worsening of mental health; acute pre-eclampsia/gestational hypertension; gestational diabetes; caesarean section; perinatal death; major congenital malformations; poor birth outcome (low birthweight, preterm birth, small for gestational age, low Apgar score); transient poor birth outcomes (tremor, agitation, breathing and muscle tone problems); and neurodevelopmental and behavioural disorders.Data sourcesClinical Practice Research Datalink database and The Health Improvement Network primary care database.ResultsPrescribing of psychotropic medication was relatively constant before pregnancy, decreased sharply in early pregnancy and peaked after delivery. Antipsychotic and anticonvulsant treatment increased over the study period. The recording of markers of worsening mental health peaked after delivery. Pregnancy was a strong determinant for discontinuation of psychotropic medication. However, between 40% and 76% of women who discontinued psychotropic medication before or in early pregnancy restarted treatment by 15 months after delivery. The risk of major congenital malformations, and neurodevelopmental and behavioural outcomes in valproate (multiple manufacturers) users was twice that in users of other anticonvulsants. The risks of adverse maternal and child outcomes in women who continued antipsychotic use in pregnancy were not greater than in those who discontinued treatment before pregnancy.LimitationsA few women would have received parts of their care outside primary care, which may not be captured in this analysis. Likewise, the analyses were based on prescribing data, which may differ from usage.ConclusionsPsychotropic medication is prescribed before, during and after pregnancy. Many women discontinue treatment before or during early pregnancy and then restart again in late pregnancy or after delivery. Our results support previous associations between valproate and adverse child outcomes but we found no evidence of such an association for antipsychotics.Future workFuture research should focus on (1) curtailing the use of sodium valproate; (2) estimating the benefits of psychotropic drug use in pregnancy; and (3) investigating the risks associated with lifestyle choices that are more prevalent among women using psychotropic drugs.Funding detailsThe National Institute for Health Research Health Technology Assessment programme.

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Section: Psychotropic Medication Prescribed Before During and After mentioning

confidence: 99%

Section: Psychotropic Medication Prescribed Before During and After mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Risks and benefits of psychotropic medication in pregnancy: cohort studies based on UK electronic primary care health records

Petersen

McCrea

Sammon

et al. 2016

Health Technol Assess

133

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Antiepileptic Drugs in Pregnancy—Quick Decisions With Long-term Consequences

Pennell

2018

JAMA Neurol

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The use of antiepileptic drugs (AED) is common in women of childbearing age. One study 1 reported that prenatal AED exposure occurred in 2.19% of all pregnancies in the United States. In the past decade, findings have highlighted that it is no longer sufficient to only consider the association between firsttrimester exposure and the risk for structural teratogenicity, because prenatal AED exposure throughout the entire pregnancy can have longterm negative consequences on neurodevelopment. The published studies are limited in scope but have consistently reported that valproate prenatal exposure is associated with lower scores on neuropsychometric batteries during early childhood, 2,3 while prenatal exposure to carbamazepine and lamotrigine monotherapies is associated with relatively normal scores. Risks associated with most other AEDs have not been adequately studied, to my knowledge.Findings from the Danish, population-based cohort study by Elkjaer et al 4 are not just additive but rather synergistic with the current body of literature, because the article provides complementary data from a unique source and study design. Prior studies have been either retrospective, case-control, registry-based, or prospective and observational, with generally low numbers of participants (eg, 13 to 62 for cohorts exposed to valproate monotherapy). 2,3,5 In contrast, the design of this study is population-based and focused on school-aged children exposed prenatally to AEDs. Children born between 1997 and 2006 were identified using the Danish Medical Birth Registry. Standardized test scores in Danish and mathematics from 479 027 children were available for analysis, including scores from 1865 children who had been exposed to AEDs prenatally. These were standardized to z scores and adjusted for calendar year, sex, maternal education level, and parental income level. The size of the sample is impressive, with 253 exposed to valproate monotherapy and substantial numbers exposed to other AEDs. The primary outcomes are objective measures based on standardized tests administered to children in second through eighth grades, with the largest data set from sixth-grade tests (mean age, 12.9 years). 4 The children with prenatal valproate exposure had lower z scores on sixthgrade Danish and mathematics tests, as well as Danish tests in the fourth and eighth grades. Even the low-dose valproate group (whose mothers took <1000 mg/day during pregnancy) had similarly reduced scores. The impact of these lower test scores on academic potential cannot be refuted. Moreover, the outcomes in the lamotrigine monotherapy group were identical to those of the unexposed group.

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Selecting contraception for women treated with antiepileptic drugs

Pennell

Davis

2015

Neurological Illness in Pregnancy

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Trends in the Use of Antiepileptic Drugs among Pregnant Women in the US, 2001–2007: A Medication Exposure in Pregnancy Risk Evaluation Program Study

Abstract: Background-Little is known about the extent of antiepileptic drug (AED) use in pregnancy, particularly for newer agents. Our objective was to assess whether AED use has increased among pregnant women in the U.S., 2001-2007.

Cited by 70 publications

References 38 publications

Risks and benefits of psychotropic medication in pregnancy: cohort studies based on UK electronic primary care health records

Risks and benefits of psychotropic medication in pregnancy: cohort studies based on UK electronic primary care health records

Antiepileptic Drugs in Pregnancy—Quick Decisions With Long-term Consequences

Selecting contraception for women treated with antiepileptic drugs

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