Increasing use of atypical antipsychotics and anticonvulsants during pregnancy

Epstein, Richard A.; Bobo, William V.; Shelton, Richard C.; Arbogast, Patrick G.; Morrow, James; Wang, Wei; Chandrasekhar, Rameela

doi:10.1002/pds.3366

Cited by 42 publications

(34 citation statements)

References 44 publications

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“…36,37,39,40,49 As we describe in a Chapter 2, there was a peak in the termination of prescribing episodes for all three classes of psychotropic medications in the first pregnancy trimester.…”

Section: Discontinuation and Factors Associated With Discontinuation mentioning

confidence: 99%

“…43 The major determinant of treatment reintroduction was relapse of the disorder, as noted from women who scored higher on depression and anxiety measures in cases where treatment was reintroduced. 39 Lithium and other mood stabilisers may on the other hand be introduced for preventative measures rather than to treat relapse. In fact, NICE guidance 12 recommends that lithium may be stopped in early pregnancy, but reintroduced in the third trimester in the case of women at high risks of relapse.…”

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: Discontinuation and Factors Associated With Discontinuation mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 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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“…70 However, as a result of relatively fewer prescriptions, information on antipsychotic safety for the fetus is much less than that available for antidepressants. Studies have suggested that antipsychotics are not or only slightly associated with increased risk of congenital malformations.…”

Section: Congenital Malformationsmentioning

confidence: 99%

Pharmacotherapy of obsessive-compulsive disorder during pregnancy: a clinical approach

Uğuz

2015

Rev. Bras. Psiquiatr.

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Obsessive-compulsive disorder (OCD) is a relatively common psychiatric disorder in the perinatal period. However, specific pharmacological treatment approaches for patients with OCD during pregnancy have not been satisfactorily discussed in the literature. In addition, there are no randomized controlled studies on the treatment of this disorder during pregnancy. The present paper discusses the pharmacological treatment of OCD in the light of data on the safety of antipsychotics and serotonergic antidepressants during pregnancy and their efficacy in the non-perinatal period. Treatment decisions should be individualized because the risk-benefit profile of pharmacotherapy is an important issue in the treatment of pregnant women with any psychiatric diagnosis.

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Comparative Safety of Antiseizure Medication Monotherapy for Major Malformations

Cohen

Alvestad

Cesta

et al. 2022

Annals of Neurology

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Objective: This study was undertaken to examine the comparative safety of antiseizure medication (ASM) monotherapy in pregnancy with respect to risk of major congenital malformations (MCMs), overall and by MCM subtype. Methods: We conducted a population-based cohort study using national health register data from Denmark, Finland, Iceland, Norway, and Sweden (1996-2020). We compared pregnancies with first trimester exposure to lamotrigine monotherapy to ASM-unexposed, carbamazepine, valproate, oxcarbazepine, levetiracetam, and topiramate to lamotrigine monotherapy, and stratified monotherapy groups by dose. The outcome was nongenetic MCM and specific subtypes. We estimated adjusted risk ratios (aRRs) and 95% confidence intervals (CIs) with log-binomial regression and propensity score weights. Results: There was a higher crude risk of any MCM in pregnancies exposed to lamotrigine monotherapy (n = 8,339) compared to ASM-unexposed pregnancies (n = 4,866,362), but not after confounder adjustment (aRR = 0.97, 95% CI = 0.87-1.08). Compared to lamotrigine, there was an increased risk of malformations associated with valproate (n = 2,031, aRR = 2.05, 95% CI = 1.70-2.46) and topiramate (n = 509, aRR = 1.81, 95% CI = 1.26-2.60), which increased in a dose-dependent manner. We found no differences in malformation risk for carbamazepine (n = 2,674, aRR = 0.91, 95% CI = 0.72-1.15), oxcarbazepine (n = 1,313, aRR = 1.09, 95% CI = 0.83-1.44), or levetiracetam (n = 1,040, aRR = 0.78, 95% CI = 0.53-1.13). Valproate was associated with several malformation subtypes, including nervous system, cardiac, oral clefts, clubfoot, and hypospadias, whereas lamotrigine and carbamazepine were not. Interpretation: Topiramate is associated with an increased risk of MCM similar to that associated with valproate, but lower doses may mitigate the risks for both drugs. Conversely, we found no increased risks for lamotrigine, carbamazepine, oxcarbazepine, or levetiracetam, which is reassuring.

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Increasing use of atypical antipsychotics and anticonvulsants during pregnancy

Cited by 42 publications

References 44 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

Pharmacotherapy of obsessive-compulsive disorder during pregnancy: a clinical approach

Comparative Safety of Antiseizure Medication Monotherapy for Major Malformations

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