Clozapine Use During Pregnancy and Lactation: A Case-Series Report

Imaz, M.L.; Oriolo, Giovanni; Torra, M.; Soy, Dolors; García-Esteve, Lluïsa; Martín‐Santos, Rocío

doi:10.3389/fphar.2018.00264

Cited by 17 publications

(16 citation statements)

References 30 publications

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“…With respect to clozapine in breast milk, the potential risks for infants are largely unknown. Imaz and coworkers 66 did not find any acute toxicological effect in newborns exposed to clozapine in pregnancy. The alternative in women who are unresponsive to other antipsychotic drugs is stopping antipsychotic treatment altogether and this, of course, confers risks of its own.…”

Section: Postpartum Psychotic Disordersmentioning

confidence: 92%

The association between hormones and antipsychotic use: a focus on postpartum and menopausal women

González-Rodríguez

Seeman

2019

Therapeutic Advances in Psychopharmacology

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During the postpartum and menopausal periods of women’s lives, there is a well-established and significant drop of circulating estrogens. This may be the reason why both these periods are associated with an increased risk for onset or exacerbation of psychiatric disorders. Whether symptoms are mainly affective or mainly psychotic, these disorders are frequently treated with antipsychotic medications, which calls for an examination of the relationship between hormone replacement and antipsychotic agents at these time periods. The aim of this narrative review is to summarize what is known about the association of hormones and antipsychotics in the postnatal period and at menopause. In the review, we focus on estrogen and oxytocin hormones and include, for the most part, only papers published within the last 10 years. Both estradiol and oxytocin have at various times been implicated in the etiology of postpartum disorders, and estrogens, sometimes combined with progesterone, have been tested as potential treatments for these conditions. The role of estradiol as an adjunct to antipsychotics in the prevention of postpartum relapses is currently controversial. With respect to oxytocin, studies are lacking. Psychosis in menopausal and postmenopausal women has been successfully treated with estrogens and selective estrogen-receptor modulators, mainly raloxifene, in addition to antipsychotics. Some symptoms appear to respond better than others. No oxytocin study has specifically targeted postmenopausal women. Because of feedback mechanisms, there is a theoretical danger of therapy with exogenous hormones interfering with endogenous secretion and disturbing the balance among inter-related hormones. When used with antipsychotics, hormones may also affect the metabolism and, hence, the brain level of specific antipsychotics. This makes treatment with antipsychotics plus hormones complicated. Dose, timing and route of intervention may all prove critical to efficacy. While much remains unknown, this literature review indicates that, within standard dose ranges, the combination of hormones and antipsychotics for postnatal and menopausal women suffering severe mental distress can be beneficial, and is safe.

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Section: Postpartum Psychotic Disordersmentioning

confidence: 92%

The association between hormones and antipsychotic use: a focus on postpartum and menopausal women

González-Rodríguez

Seeman

2019

Therapeutic Advances in Psychopharmacology

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“…The treatment generally includes sequential administration of short-term benzodiazepines, antipsychotics, and lithium, with response monitoring. 22 …”

Section: Discussionmentioning

confidence: 99%

“…Cases of long-term treatment-resistant psychoses with onset during the postpartum period have been reported and a few studies have explored the efficacy of electroconvulsive therapy, but data sustaining the best therapeutic attitude for these cases is lacking. 22 , 23 …”

Section: Discussionmentioning

confidence: 99%

Clozapine Efficacy in a Case of Severe Treatment-Resistant Postpartum Psychosis

Teodorescu

Ifteni

Dragan

et al. 2021

RMHP

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Background The postpartum period is a difficult time for mother and family. Unfortunately, in some cases, two psychiatric complications may occur: postpartum psychoses (PPP) with a prevalence of 0.2% and a very low incidence of 0.25–0.50 per 1000 deliveries, and post-natal depressions with an incidence of 10 to 20% per 1000 deliveries. The onset of postpartum psychosis is in the first 4 weeks after childbirth with symptoms such as emotional lability, cognitive disorganization, delusional beliefs and hallucinations. It requires hospitalization due to the high risk of suicide and infanticide. The studies reveal that the treatment can include FGAs (first-generation antipsychotics), such as haloperidol, and SGAs (second-generation antipsychotics), such as olanzapine, quetiapine and risperidone. The literature is scarce in what resistant PPP is concerned and no such cases treated with clozapine have been reported, according to our knowledge. The present case report focuses on a female diagnosed with PPP who was treated with clozapine due to the lack of response to adequate dosage of 2 second-generation antipsychotics. Case Presentation We present the case of a 30-year-old primiparous woman on her 3rd day after delivery, admitted in the psychiatric emergency unit for agitation, intrusive thoughts with a content frequently related to the infant, ideas of reference, disorganized speech, bizarre behavior, verbal stereotypes, insomnia and anxiety. Due to lack of response to adequate dosage of 2 second-generation antipsychotics, clozapine was initiated up to 250 mg/day. The symptoms remitted in the next 5 days and the patient was discharged. After discharge, at the patient’s request, clozapine was replaced by olanzapine. Visit at 1 year revealed full remission of symptoms. Conclusion Although data is extremely limited, clozapine has been shown to be effective and safe in a severe case of treatment-resistant PPP.

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“…The F:M concentration ratios of clozapine, the first atypical antipsychotic developed, varied from 0.39 to 0.58, as reported by Imaz et al, whereas Barnas et al found a much higher value of 1.91. 80,81 These values result in a geometric mean of 0.64 (n = 5). The active metabolite of clozapine, norclozapine, has F:M concentration ratios ranging between 0.21 and 0.37 (geometric mean = 0.29, n = 4).…”

Section: Atypical Antipsychoticsmentioning

confidence: 99%

Antidepressants and Antipsychotics in Human Pregnancy: Transfer Across the Placenta and Opportunities for Modeling Studies

Zheng

Yang

Dallmann

2022

The Journal of Clinical Pharma

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There is limited information about the transfer of antidepressants and antipsychotics across the human placenta. The objective of the current review was to systematically screen the scientific literature using relevant keywords to collect quantitative data on placental transfer of these drugs in humans and to give an overview of current modeling approaches used in this context. The collected data encompassed clinically measured fetal:maternal (F:M) concentration ratios (ie, the ratio between drug concentrations measured in the umbilical cord and drug concentrations measured in the mother) and transfer data obtained from ex vivo cotyledon perfusion experiments. These data were found for 18 antidepressants and some of their pharmacologically active metabolites, and for 10 antipsychotics and the metabolites thereof. Based on the collected data, similar maternal and fetal exposure could be observed for only a few compounds (eg, norfluoxetine and desvenlafaxine), whereas for most drugs (eg, paroxetine, sertraline, and quetiapine), fetal exposure appeared to be on average lower than maternal exposure. Venlafaxine appeared to be an exception in that the data indicated equivalent or higher concentrations in the umbilical cord than in the mother. Physiologically based pharmacokinetic (PBPK) models were sporadically used to investigate maternal pharmacokinetics of antidepressants or antipsychotics (eg, for sertraline, aripiprazole, and olanzapine), although without explicitly addressing fetal drug exposure. It is recommended that PBPK modeling is applied more frequently to these drugs. Although no substitute for clinical studies, these tools can help to better understand pregnancy‐induced pharmacokinetic changes and ultimately contribute to a more evidence‐based pharmacotherapy of depression and psychosis in pregnant subjects.

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Clozapine Use During Pregnancy and Lactation: A Case-Series Report

Cited by 17 publications

References 30 publications

The association between hormones and antipsychotic use: a focus on postpartum and menopausal women

The association between hormones and antipsychotic use: a focus on postpartum and menopausal women

Clozapine Efficacy in a Case of Severe Treatment-Resistant Postpartum Psychosis

Antidepressants and Antipsychotics in Human Pregnancy: Transfer Across the Placenta and Opportunities for Modeling Studies

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