Obstetric and neonatal outcomes of clozapine exposure in pregnancy: a consecutive case series

Nguyen, Tien; Mordecai, Jasmine; Watt, Felice; Frayne, Jacqueline

doi:10.1007/s00737-019-00985-1

Cited by 10 publications

(3 citation statements)

References 12 publications

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“…Crucially, the models also suggested that plasma concentrations of quetiapine in the third trimester were mostly below therapeutic range (100 ng/mL), whereas aripiprazole did not reach its effective concentration (150 ng/mL), suggesting adjustments to doses may be particularly needed in the later stages of pregnancy. A similar recommendation came also for clozapine from observations in a case series [28 ▪ ]. Here, the authors found an increase in serum clozapine levels in the third trimester in two of the three women for whom these were available, which suggests that although close blood monitoring is recommended across all stages, it may be required even more consistently in the later stages of pregnancy.…”

Section: Implications For Treatmentsupporting

confidence: 68%

“…Furthermore, the authors found that even when controlling for maternal age and obesity, four antipsychotics (risperidone, clozapine, higher-dose quetiapine, and olanzapine at trend level) were associated with an increased risk of developing gestational diabetes [36 ▪▪ ]. For clozapine, this was the case also in the aforementioned case series of nine women exposed to clozapine in pregnancy [28 ▪ ], where two-thirds had gestational diabetes mellitus and high rates of obesity. These women also developed other negative obstetric outcomes, with infants with poor neonatal adjustment that often required neonatal resuscitation.…”

Section: Obstetric and Infant Outcomesmentioning

confidence: 83%

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Schizophrenia during pregnancy

Dazzan¹

2021

Current Opinion in Psychiatry

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Purpose of reviewA diagnosis of schizophrenia has significant implications for women of childbearing age, pregnant or considering a pregnancy, ranging from sexual health, psychopharmacological treatment, to the occurrence of negative pregnancy and foetal outcomes. We provide a short narrative review of recent papers focusing on these issues. Recent findingsAlthough pregnancy rates have been increasing in women with a diagnosis of schizophrenia, they also tend to have altogether fewer pregnancies and fewer live births than women without this diagnosis, and also higher rates of induced abortions. Use of antipsychotics in pregnancy has also increased, and evidence suggests lack of significant contraindications for their use in this period. However, drug levels monitoring may be recommended across the three trimesters, as levels may change in relation to pregnancy-related physiology. Monitoring of physical health is an increasingly crucial issue, given higher risk of gestational diabetes, negative obstetric and infant outcomes in these women. SummaryThere is an urgent need to generate valid and reproducible research that could help implement appropriate treatment protocols and relapse-prevention approaches, and interventions based on strong pharmaceutical targets for the benefit of pregnant women with a diagnosis of schizophrenia, their families and their children.

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Section: Implications For Treatmentsupporting

confidence: 68%

Section: Obstetric and Infant Outcomesmentioning

confidence: 83%

Schizophrenia during pregnancy

Dazzan¹

2021

Current Opinion in Psychiatry

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“…Although research on this topic is limited, these metabolic changes appear to have significant consequences on the plasma levels of CYP3A4/CYP2D6 substrates quetiapine (in 35 pregnancies) and aripiprazole (in 14 pregnancies), which were found to be reduced by more than 50% in the third trimester whereas plasma levels of olanzapine (in 29 pregnancies) and clozapine (in 4 pregnancies) were found to be unchanged (Westin et al, 2018). For clozapine, there is some evidence for increased serum levels in the third trimester (Nguyen, Mordecai, Watt, & Frayne, 2020). Summarising, drug monitoring and blood level assessment is required throughout pregnancy and becomes increasingly important in the third trimester (Table 2) (Dazzan, 2021).…”

Section: Dosing During Pregnancymentioning

confidence: 99%

Antipsychotic medication for women with schizophrenia spectrum disorders

et al. 2021

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There are significant differences between men and women in the efficacy and tolerability of antipsychotic drugs. Here, we provide a comprehensive overview of what is currently known about the pharmacokinetics and pharmacodynamics of antipsychotics in women with schizophrenia spectrum disorders (SSDs) and translate these insights into considerations for clinical practice. Slower drug absorption, metabolism and excretion in women all lead to higher plasma levels, which increase the risk for side-effects. Moreover, women reach higher dopamine receptor occupancy compared to men at similar serum levels, since oestrogens increase dopamine sensitivity. As current treatment guidelines are based on studies predominantly conducted in men, women are likely to be overmedicated by default. The risk of overmedicating generally increases when sex hormone levels are high (e.g. during ovulation and gestation), whereas higher doses may be required during low-hormonal phases (e.g. during menstruation and menopause). For premenopausal women, with the exceptions of quetiapine and lurasidone, doses of antipsychotics should be lower with largest adjustments required for olanzapine. Clinicians should be wary of side-effects that are particularly harmful in women, such as hyperprolactinaemia which can cause oestrogen deficiency and metabolic symptoms that may cause cardiovascular diseases. Given the protective effects of oestrogens on the course of SSD, oestrogen replacement therapy should be considered for postmenopausal patients, who are more vulnerable to side-effects and yet require higher dosages of most antipsychotics to reach similar efficacy. In conclusion, there is a need for tailored, female-specific prescription guidelines, which take into account adjustments required across different phases of life.

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Mental Health and Illness of Women

Nguyen

Desai

2019

Mental Health and Illness Worldwide

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Obstetric and neonatal outcomes of clozapine exposure in pregnancy: a consecutive case series

Cited by 10 publications

References 12 publications

Schizophrenia during pregnancy

Schizophrenia during pregnancy

Antipsychotic medication for women with schizophrenia spectrum disorders

Mental Health and Illness of Women

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