Risk of Major Malformations in Infants Following First-Trimester Exposure to Quetiapine

Cohen, Lee S.; Góez-Mogollón, Lina; Sosinsky, Alexandra Z.; Savella, Gina M.; Viguera, Adele C.; Chitayat, David; Hernández–Dı́az, Sonia; Freeman, Marlene P.

doi:10.1176/appi.ajp.2018.18010098

Cited by 31 publications

(26 citation statements)

References 22 publications

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“…Results show an absolute risk of 3.13% (N = 96), not different from the risk associated with exposure to any SGA antipsychotic, 1.3% (N = 312), or unexposed infants, 0.6% (N = 177). 133 Though, small sample sizes and wide confidence intervals may have obfuscated actual differences. These data corroborate an earlier study in pregnant women taking aripiprazole (N = 86 vs 172 unexposed).…”

Section: Pharmacology and Adverse Eventsmentioning

confidence: 99%

Classics in Chemical Neuroscience: Aripiprazole

Casey

Canal

2017

ACS Chem. Neurosci.

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Aripiprazole was the first antipsychotic developed to possess agonist properties at dopamine D2 autoreceptors, a groundbreaking strategy that presented a new vista for schizophrenia drug discovery. The dopamine D2 receptor is the crucial target of all extant antipsychotics, and all developed prior to aripiprazole were D2 receptor antagonists. Extensive blockade of these receptors, however, typically produces extrapyramidal (movement) side effects which plagued first-generation antipsychotics, such as haloperidol. Second-generation antipsychotics, such as clozapine, with unique polypharmacology and D2 receptor binding kinetics, have significantly lower risk of movement side effects, but can cause myriad additional ones, such as severe weight gain and metabolic dysfunction. Aripiprazole’s polypharmacology—characterized by its unique agonist activity at dopamine D2, D3 and serotonin 5-HT1A receptors as well as antagonist activity at serotonin 5-HT2A receptors—translates to successful reduction of positive, negative, and cognitive symptoms of schizophrenia, while also mitigating risk of weight gain and movement side effects. New observations, however, link aripiprazole to compulsive behaviors in a small group of patients, an unusual side effect for antipsychotics. In this review, we discuss the chemical synthesis, pharmacology, pharmacogenomics, drug metabolism, and adverse events of aripiprazole, and we present a current understanding of aripiprazole’s neurotherapeutic mechanisms, as well as the history and importance of aripiprazole to neuroscience.

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Section: Pharmacology and Adverse Eventsmentioning

confidence: 99%

Classics in Chemical Neuroscience: Aripiprazole

Casey

Canal

2017

ACS Chem. Neurosci.

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“…Antipsychotic use in pregnancy has increased in recent years (Park et al, 2017; Toh et al, 2013), yet the risks and benefits are not clear. While some studies have found an increased risk of congenital malformations (Coughlin et al, 2015; Habermann et al, 2013), most robustly designed studies have found little evidence of an increased risk (Chisolm and Payne, 2016; Cohen et al, 2018; Huybrechts et al, 2016; Petersen et al, 2016). However, abrupt discontinuation of antipsychotic treatment can lead to relapse during pregnancy or the postpartum period (Taylor et al, 2018; Viguera et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

“…However, abrupt discontinuation of antipsychotic treatment can lead to relapse during pregnancy or the postpartum period (Taylor et al, 2018; Viguera et al, 2011). Moreover, typical (first generation) antipsychotics have been linked to low birth weight and preterm delivery (Habermann et al, 2013), and atypical (second generation) antipsychotics are associated with maternal weight gain, gestational diabetes and increased infant size (Chisolm and Payne, 2016; Cohen et al, 2018). Establishing a causal association between antipsychotic use and poor birth outcomes is challenging, as bipolar disorder and schizophrenia are both associated with an increased risk of adverse birth outcomes regardless of treatment (Boden et al, 2012b; Kang-Yi et al, 2017; Tosato et al, 2017) and pregnant women with mental illness have high rates of smoking, substance abuse, use of multiple psychotropic medicines and obesity, all important risk factors for pregnancy complications (Chisolm and Payne, 2016).…”

Section: Introductionmentioning

confidence: 99%

Trajectories of antipsychotic use before and during pregnancy and associated maternal and birth characteristics

Schaffer

Zoëga

Tran

et al. 2019

Aust N Z J Psychiatry

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Objective: To identify distinct trajectories of antipsychotic use prior to and during pregnancy and describe the associated maternal and birth characteristics. Methods: We conducted a population-based cohort study of births (2005–2012) using linked administrative data in New South Wales, Australia. We used group-based trajectory modelling to classify trajectories of antipsychotic use in the 450 days prior to pregnancy and during pregnancy. We characterised women with different trajectories according to maternal sociodemographic characteristics, mental health diagnoses and hospitalisations, use of psychotropic medicines and birth outcomes. Results: Of 137,993 women who gave birth, 2741 (2.0%) were exposed to antipsychotics prior to or during pregnancy. We identified six trajectories of antipsychotic use: two involved short-term use of low daily doses prior to pregnancy (51.1%), while three involved long-term use of low (20.9%), moderate (11.0%) and high (2.0%) daily doses throughout pregnancy. One trajectory (15.0%) involved increasing use during pregnancy. Women with long-term use were more likely to have a schizophrenia or bipolar disorder diagnosis, to have used multiple psychotropics and to have a mental health hospitalisation during pregnancy. Overall, women using antipsychotics had elevated rates of adverse birth outcomes compared to unexposed women. Women with the greatest antipsychotic exposure had the highest rates of gestational diabetes and gestational hypertension. Conclusion: Women using antipsychotics around pregnancy are heterogeneous, with varying patterns of use and associated birth outcomes, reflecting underlying differences in the indications for treatment and/or severity of illness. This diversity should be considered when developing clinical guidelines and designing safety studies.

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“…Literature suggests monthly clinical evaluation in order to detect the symptoms of depressive or maniacal episodes and to adjust the dose of quetiapine accordingly (85). The drug has not been related to major malformations (86,87).…”

Section: Second-generation Antipsychotics (Sgas)mentioning

confidence: 99%

Affective disorders: A question of continuing treatment during pregnancy (Review)

2020

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Fetal development, especially in the first trimester, has proven to be heavily influenced by external factors, such as chemical intake of medication. Chronic psychiatric treatment might interfere with the anatomical and physiological wellbeing of the fetus, because psychotropic medication proceeds past the placenta, into the amniotic fluid, and can enter breast milk. Hence some of the medications prescribed for mood disorders should be reconsidered during pregnancy, without sub-optimally treating when it is needed. A literature review is presented which systematically collects modern data and synthesizes previous interdisciplinary research findings on the safety of psychiatric treatment for affective disorders during pregnancy (term-based) and lactation. Antidepressants and mood stabilizers, fundamental strategies in treating affective disorders, have been classified by the FDA as C respectively D drugs pertaining to their risk, with some exception. Most guidelines recommend pharmacologically treating moderate-severe depression, preferably with SSRIs. Evidence advocates that drugs should be used during pregnancy only if clearly needed and the benefit outweighs the risk to the fetus. However, guidelines the American College of Obstetricians and Gynecologists state that antidepressants are a preferred first course of treatment and does not take into account the severity of the depression. Among mood-stabilizers, lithium is considered to be the safest option for pregnant women. Anticonvulsants have a higher risk of teratogenicity compared with lithium, with lamotrigine being the safest one. All mood stabilizers should be recommended in the lowest effective doses. There is controversy regarding the safety of second-generation antipsychotics during pregnancy and further research is required. Several case reports and meta-reviews have been published in order to emphasize the safety of electroconvulsive therapy (ECT) during pregnancy, but practitioners still stigmatize this procedure. Evaluating the overall risk-benefit ratio should be assessed by the medical care provider, taking into consideration current findings.

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Risk of Major Malformations in Infants Following First-Trimester Exposure to Quetiapine

Cited by 31 publications

References 22 publications

Classics in Chemical Neuroscience: Aripiprazole

Classics in Chemical Neuroscience: Aripiprazole

Trajectories of antipsychotic use before and during pregnancy and associated maternal and birth characteristics

Affective disorders: A question of continuing treatment during pregnancy (Review)

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