McCauley-Elsom and Kulkarni (2007) provide an overview of a case study of a 36-year-old mother of three with a 5-year history of schizophrenia who was pregnant for the fourth time. The woman was well during her pregnancy and continued to take prescribed risperidone and consulted her GP regularly, with whom she had a very good rapport. At 37 weeks, labour was induced due to concerns regarding the baby’s failure to grow. She gave birth to a 2.2 kg female who was transferred to a special care nursery due to feeding and thermoregulation problems as well as hyperbilirubinaemia. The baby was discharged to the mother at 6 weeks. At 12 weeks postnatal, the woman attended a new GP for an unstated reason, and the doctor recommended she cease all medications. As a result, the woman’s mental state deteriorated and she was admitted to an inpatient mental health unit 5 weeks later and separated from her baby.

Questions:

» What went wrong here?

» Who could have helped prevent the outcome in this case?

» How can we ensure this type of event does not occur in the future? Remember to consider all health professionals involved and the need for collaboration between health team members.

» Take the time to access and read the entire case study contained in this paper.

Evidence of the teratogenic effects of psychotropic medications is mixed, and their use during pregnancy is a concern because of the exposure of the fetus to an increased risk of congenital malformation. Psychotropic medications readily cross the placenta. The major time of danger for such exposure is the first trimester, although the first 8 weeks appear to be the most significant. Risks from in-utero exposure include spontaneous abortion, structural malformations, carcinogenesis, intrauterine growth retardation, immediate neonatal effects, withdrawal symptoms and behavioural toxicity (Trixler & Tenyi 1997).

Use of antipsychotics during pregnancy

Higher potency first generation antipsychotics such as haloperidol have not been associated with any increased risk of congenital malformations. Low potency first generation antispychotics, such as chlorpromazine, are usually not prescribed due to concerns about side effects such as hypotension and their association with a slightly higher risk of malformations (Grover et al 2006). Evidence of a perinatal syndrome associated with first generation antipsychotics has been described. These babies demonstrate symptoms of respiratory depression, difficulty feeding, ‘floppy baby’ syndrome, hypertonicity, sluggish primitive reflexes, extrapyramidal symptoms, tremor, abnormal movements, irritability and agitation. However, the symptoms tend to dissipate within a few days (Yaeger et al 2006). Second generation antipsychotics, rapidly becoming the medication of choice for many people with schizophrenia, do not tend to have some of the side effects of the older, first generation antipsychotics and appear to result in better short- and long-term responses. However, the appropriateness of their use in pregnancy remains unresolved as the limited number of studies is currently inadequate to determine their safety. Therefore, pregnant women prescribed these medications are usually changed to a first generation antipsychotic during pregnancy (Grover et al 2006, Ward & Wisner 2007). A recent study of second generation antipsychotic medications in pregnant women, however, found no statistical differences in the rates of miscarriage, stillbirth, prematurity, congenital malformations and perinatal syndromes in relation to healthy comparison subjects. The study did find an increased rate of babies with low birth weight and, in the mothers, higher body mass index and a greater number of elective abortions. There are concerns that clozapine may be associated with a high rate of congenital malformations. Additional concerns include the known risks of agranulocytosis and orthostatic hypotension associated with clozapine use, which may also have serious effects on the unborn fetus (Yaeger et al 2006).

Use of medications for depression and bipolar disorder during pregnancy

The efficacies of medications used to treat depression and mania have also been studied. There have been concerns about the association between prenatal exposure to lithium and the risk of major congenital abnormalities for more than four decades. Congenital abnormalities recorded include cardiovascular malformations (particularly Ebstein’s anomaly), large for gestational age infants, anencephaly and oromandibular-limb hypogenesis. Other risks include muscular hypotonia with impaired breathing and cyanosis (often referred to as ‘floppy baby’ syndrome), isolated cases of hypothyroidism, nephrogenic diabetes insipidus and polyhydramnios (Grover et al 2006, Ward & Wisner 2007). However, lithium is by far the safest of the anti-manic medications available for use in pregnancy (Ward & Wisner 2007). Compared to lithium, anticonvulsants used to treat mania pose a much more serious threat and should be avoided wherever possible during pregnancy. Carbamazepine has been associated with craniofacial abnormalities, microcephaly, growth retardation, spina bifida, cardiac abnormalities, fingernail hyperplasia and developmental delay. Valproate has been associated with neural tube deficits (particularly those that occur within the first month of gestation), hydrocephalus, cardiovascular malformations, limb defects, genital anomalies and intrauterine growth retardation. The use of valproate near the time of delivery also causes problems for the newborn infant such as jitteriness, feeding difficulties, irritability, heart rate deceleration, hypoglycaemia and abnormal tone (Grover et al 2006, Ward & Wisner 2007). Prenatal use of tricyclic antidepressants or the newer selective serotonin reuptake inhibitors (SSRIs) used to treat depression does not appear to increase the risk of congenital abnormalities although these agents can cause minor complications if used close to the time of delivery. For example, studies have found evidence of poor neonatal adaptation syndrome, which includes tremors, jitteriness, shivering, feeding or digestive problems and respiratory distress. These problems were, however, relatively minor and short-lived (Way 2007). In general, the SSRIs are preferred to the tricyclic antidepressants (Sved Williams 2007). The only antidepressant that may be unsuitable for use during pregnancy is paroxetine. Recent research indicates that there may be a small risk of congenital abnormalities, especially cardiac defects, related to the use of paroxetine during pregnancy (Way 2007). To date the evidence for venlafaxine indicates it is safe to use during pregnancy but, although it is not associated with a higher rate of birth defects, it has been linked to increased rates of spontaneous abortion. According to the data available on the use of mirtazapine during pregnancy, it should be avoided (Sved Williams 2007). Monoamine oxidase inhibitors (MAOIs) are considered best avoided because of the risk of hypertensive crises.

Use of other psychotropics during pregnancy

The benzodiazepines, psychotropic medications commonly used as an adjunct treatment for mood stabilisation, anxiety, agitation and sleep disorders, also readily cross the placenta and may pose a risk to the fetus. The risk of malformations from this class of medication is highest during the first 8 weeks of pregnancy. Medications of this type administered close to the time of delivery have also been linked to fetal dependence and withdrawal symptoms. The use of diazepam during pregnancy is considered safe, and evidence indicates that the use of this medication during pregnancy causes no harm to the fetus (Iqbal et al 2002). The use of other benzodiazepine medications such as clonazepam, lorazepam and alprazolam has, however, been linked to serious congenital abnormalities and thus should be avoided during the first trimester of pregnancy (Grover et al 2006).

Usher, Foster and MacNamara (2005) proposed guidelines for the use of antipsychotic medication by women who are pregnant (see Box 7.1) or breastfeeding. These include the following:

• Antipsychotics, including depot injections, should be avoided in the first trimester.

• Women using second generation antipsychotics should change to first generation antipsychotics as soon as pregnancy is diagnosed.

• Pregnant and breastfeeding women should be prescribed the lowest possible dose.

• Depot injections should be avoided with breastfeeding women.

• Only infants born at full term should be exposed to the potential to ingest medication via breast milk (see Thinking challenge 7.2).

Thinking challenge 7.2

Many community-based health professionals may be involved in advising a pregnant woman about the issues of taking psychotropic medications during pregnancy. How do you think you would advise someone in this situation? What are the main issues to be considered when weighing up the risks to the mother and fetus and how would you relate these in your clinical interview? List the special issues that may be relevant to your clinical role versus other members of the health care team.

Given the risks associated with the use of psychotropic medications during pregnancy, it is imperative that members of the health care team are aware of the medications that must be avoided and work together to ensure all other available strategies have been explored before psychotropic medications are prescribed (see Clinical alert 7.1). If prescribed, the lowest dose possible for the shortest period of time is recommended, and regular, individual assessments of the risks and benefits that fully involve the woman and her family should be made. Monitoring of the woman at regular intervals during the pregnancy and after the birth is important to ensure the ongoing wellbeing of both the mother and baby.

The use of psychotropic medications when breastfeeding

Women with pre-existing mental disorders may continue to require the prescription and administration of psychotropic medications after childbirth. Evidence indicates that 10–15% of all postpartum women will develop some form of mental disorder (Winans 2001, Oates 2003), and those women with a pre-existing condition are at a higher risk of developing a relapse in the postnatal period (Ilett et al 2004). These women may also require psychotropic medications. Of relevance here is the relation to the woman’s decision to breastfeed her infant, a normal and highly recommended practice (Malone et al 2004) whose benefits are well documented. The relationship between breastfeeding and mental disorders, especially postnatal depression, is complex. Women who develop depression are considered more likely to cease breastfeeding. However the converse is also true as women who establish and maintain breastfeeding are found to be less likely to become depressed than women who experience difficulties with breastfeeding (Sved Williams 2007). Decisions to prescribe or administer psychotropic medications should weigh up the woman’s preference to breastfeed and the risk to the infant versus the benefit to the mother. The decisions should be made in a collaborative way, including all members of the health care team, after the woman and her partner/family have been fully informed of the risks and benefits of the medication.

Overall, the available research on the safety of psychotropic medications when breastfeeding is limited and fraught with confounding variables. Most psychotropic medications pass into breast milk but there is a significant variation in the amount actually received by the infant. The plasma level of the medication in the neonate involves various factors such as the medication level at birth (when the mother was taking the medication prior to delivery), the relative degree of transfer of the medication to the breast milk, the half-life of the drug, the protein binding ability of the drug, time of peak serum concentration in the mother and its relation to feeding and the amount of milk produced and ingested by the infant (Hale 2004, Usher & Foster 2006). We do know that the transfer of psychotropic medications to breast milk is less efficient than placental transfer (i.e., blood-to-blood in pregnancy versus blood-to-milk-to-gut-to-blood in breastfeeding) (Stowe 2007). Therefore, the risk of these medications to the breastfed newborn may be lower than during pregnancy but a risk nevertheless.

Use of antipsychotics during breastfeeding

Available evidence indicates that all antipsychotic medications are excreted into breast milk (see Clinical alert 7.2). Lactation studies with first generation antipsychotic medications have consistently reported low milk to plasma transfer levels (< 1) (Jain & Lacy 2005). However, it has been recommended that the phenothiazine group of first generation antipsychotics be avoided wherever possible because of their potential for neonatal apnoea and sedation (Hale 2004). Clozapine, found at high levels in infants at the time of delivery but significantly reduced after 1 week, is not recommended during breastfeeding. Case reports have identified problems such as sedation, cardiovascular instability and agranulocytosis (Jain & Lacy 2005). Studies of the effects of olanzapine on 21 breast-fed infants revealed five reports of adverse effects including jaundice, cardiomegaly, heart murmur, shaking, lethargy, poor sucking, protruding tongue, rashes, diarrhoea and sleeping problems. Studies of risperidone and quetiapine have shown no adverse effects so far (Ernst & Goldberg 2002).

Clinical alert 7.2 Use of antipsychotics when breastfeeding

All antipsychotic medications are excreted into breast milk and therefore have some impact on the breastfed neonate.

This is important to remember when advising the mother and her partner.

Use of antidepressants during breastfeeding

Overall, there have been relatively few studies demonstrating adverse effects in infants exposed to antidepressants via breast milk. The tricyclic antidepressants, now only used minimally, are relatively safe to use when breastfeeding. The SSRIs are commonly the first choice for pregnant and breastfeeding women because they tend to cause fewer autonomic and other side effects and because the rate of transfer to, and uptake by, the baby is relatively low (Hale 2004). Venlafaxine is, however, thought to accumulate in the breastfed baby so it is therefore not recommended for prolonged use (Sved Williams 2007). Case reports of adverse effects from trazodone and bupropion have also been reported but it is considered too soon to draw any firm conclusions about the safety of those medications during breastfeeding. It has been recommended that fluoxetine (due to its long half-life) and high doses of citalopram (because of high plasma and breast milk concentrations) be avoided except in women who have demonstrated good outcomes with the medication during pregnancy. The research to date shows low or undetectable levels with sertraline, paroxetine and fluvoxamine (Payne 2007). It is important to weigh up the benefits of the antidepressant medications against the risks of untreated postnatal depression. As well as the risk to the mother, failure to adequately treat maternal depression can result in poor mother–baby bonding, potential effects on the child’s intelligence level and delayed development (Payne 2007) (see Chat box 7.1).

Chat box 7.1

Exposure of a child to postpartum depression should be considered an exposure in the same way that taking an antidepressant while breastfeeding is an exposure.

(Payne 2007, p 1330)

This is an interesting quote. What is the point being made and why has the author felt the need to make it? Consider how it relates to decisions women and their partners must make in these situations. What are the particular implications for your clinical role?

Use of other psychotropics during breastfeeding

Lithium may have been unfairly rated as unsuitable for use when breastfeeding infants due to the potential for adverse effects (Stowe 2007). Recent studies found serum lithium levels in nursing infants to be low and well tolerated. Further, there were no significant adverse clinical or behavioural effects noted (Viguera et al 2007). Lithium is thus considered relatively safe in compliant mothers, but the infants must receive regular monitoring for serum lithium concentrations as well as renal and thyroid function (Sved Williams 2007). The anticonvulsants used to treat mood disorders, carbamazepine and valproate, are also considered safe for use in breastfeeding women.

The use of benzodiazepines while breastfeeding is not recommended (see Box 7.2). These medications have been found to accumulate in breast milk and in the infant. While single doses of the medication may be acceptable, ongoing use should be avoided (Usher & Foster 2006). Signs of toxicity include lethargy, hypotonia, poor feeding and sedation.