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PERINATAL MENTAL HEALTH PART II
AMELLIA KAPA COMMUNICATIONS ADVISOR
perinatal mental health in aotearoa
part II: medications and implications
Part I of the perinatal mental health series provided an overview of the current landscape in Aotearoa, discussing the midwife’s role, including screening. Part II focuses on commonly prescribed psychotropic medications and considerations for midwives when discussing their potential implications with wāhine/whānau.
BACKGROUND He Ara Oranga, the 2018 report on the Government inquiry into Mental Health and Addiction Services in New Zealand, states that the number of general prescriptions for mental health-related medications increased by 50% over the previous 10 years, and was continuing to rise at a rate of around 5% each year at the time of the report’s publication (Government Inquiry into Mental Health and Addiction, 2018).
In the same vein, a University of Otago study published this year which aimed to describe and compare antidepressant dispensing patterns before, during and after pregnancy in New Zealand between 20052014, reveals an antidepressant was dispensed in 3.1% of pregnancies in 2005, rising to 4.9% by 2014 (Donald et al., 2021).
The study, which linked antidepressant dispensing records with 805,990 pregnancies over the nine-year period, also demonstrated a clear pattern; dispensing during the first trimester dropped to below pre-pregnancy and post-pregnancy levels, and the number fell even further in the second and third trimesters. This data would indicate women in Aotearoa who have been taking antidepressants prior to pregnancy are stopping, or significantly reducing their use of the medication during pregnancy.
This finding is consistent with international data, including a Danish retrospective cohort study which showed that despite an overall increase of exposure to antidepressants in pregnancy in Denmark from 0.2% in 1997 to 3.2% in 2010, rate of exposure halved during the first trimester (Jimenez-Solem et al., 2013). A UK study mirrored these findings, revealing 79.57% of 19,774 women who were taking a psychiatric medication pre-conception, discontinued it in pregnancy (Margulis, Kang & Hammad, 2014). It is thought that hesitancy from both the practitioner to prescribe, and the woman to accept psychotropic medications in pregnancy, may be responsible for the sharp drop off, but both the Danish and New Zealand studies acknowledged the need for further research into the possible contributing factors (Jimenez-Solem et al., 2013).
Donald et al.’s (2021) analysis also showed that younger women, and those of Māori, Pacific, or Asian ethnicity were less likely to continue therapy during pregnancy if they were taking an antidepressant preconception. In their discussion, it was noted that whilst the prevalence of depression and anxiety in European and Māori women is similar, Māori women in the study were only dispensed an antidepressant around half as often as their European counterparts.
Furthermore, Pacific and Asian women were only one-fifth as likely as European women to be dispensed an antidepressant, despite the fact that a longitudinal study has found that depressive symptoms during pregnancy were twice as likely to be experienced by the same group when compared with European women (Waldie et al., 2015). Donald et al. (2021) acknowledge that one possible explanation for the disparity in figures could be the potential for use of non-pharmacological therapies being higher in non-European ethnic groups, but do not discount the well-documented disparities in health service accessibility as possible contributing factors, nor the differences in cultural values regarding mental illness.
Ethnicity aside, given that evidence has shown fetal antidepressant exposure may carry a small increased risk of preterm birth, congenital cardiac abnormalities, and persistent pulmonary hypertension of the newborn, hesitancy from a woman’s perspective is hardly surprising, and midwives may find themselves facing this situation in practice (Donald et al., 2021).
COMMONLY PRESCRIBED MEDICATIONS Around 80% of dispensings in the Otago University study were for selective serotonin reuptake inhibitors (SSRIs) (Donald et al., 2021). Consultant psychiatrist and Clinical Head of the Mother and Babies Service at Canterbury District Health Board, Dr Liz MacDonald, has been working in the field of perinatal psychiatry for 20 years and corroborates this, naming SSRIs as the most commonly prescribed class in her experience. She cites sertraline and escitalopram as two well-known examples midwives will be familiar with.
Less commonly, she explains, antidepressants from other groups such as serotonin noradrenaline reuptake inhibitors (SNRIs) may be prescribed, such as venlafaxine. And at times, older tricyclics such as nortriptyline might be used.
The choice of medication will depend on the individual and their overall clinical picture. “Antidepressants can be prescribed for use in anxiety, as well as depression. When choosing an antidepressant, we consider things such as previous response to medication and the properties of the medication. For example, a woman that is having difficulty sleeping might benefit from being on an antidepressant with sedative effects.”
For severe anxiety, Liz says additional short-term medications like benzodiazepines may be used, such as lorazepam. And rarely, a woman suffering from severe depression or bipolar disorder might be prescribed lithium, used to treat depression and stabilise mood.
Similar to the choice of medication, dosage will fluctuate throughout the population and over the course of a pregnancy, but caution is exercised to ensure minimal exposure for maximum therapeutic effect. “Dosage varies a lot depending on the severity and nature of the illness, and the woman’s own individual response and tolerance of the medication. However, in general the minimum dose to manage the symptoms should be used, with the goal of effective treatment for the woman, and avoiding unnecessary exposure for the unborn baby. Sometimes in the third trimester of pregnancy, the dosage may need to be increased, due to metabolic changes of pregnancy which ‘dilute’ the effective dose available,” Liz explains.
The same approach of prescribing minimum doses to manage symptoms is used with breastfeeding mothers, but Liz advises newborns are generally less exposed than a fetus in utero, due to the fact that many of the antidepressants used postnatally are secreted in breastmilk in relatively small quantities.
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IMPLICATIONS FOR NEWBORNS Exposure to SSRIs, SNRIs and tricyclics in utero may increase the risk of the newborn experiencing transient issues adapting to extrauterine life (CDHB 2017; Gentile, 2014).
Whilst Liz maintains the need to balance these risks with the potential consequences of not managing depression and anxiety successfully, she details the most common concerns for newborns.
“The main issue that people need to be aware of for the antidepressants is neonatal adaptation difficulties in the newborn period. This is a collection of symptoms seen in some neonates exposed to psychotropic medicines in utero, particularly with antidepressants and antipsychotics. Whether the symptoms relate to adverse effects of the medicine, or a withdrawal phenomenon, is often not clear.”
Symptoms of Neonatal Adaptation Syndrome (NAS) may include:
• poor feeding/suckling diffculties, vomiting or diarrhoea
• restlessness, irritability or lethargy/drowsiness
• tremors, hyper/hypotonia, hyperreflexia
• nasal congestion, tachypnoea
• body temperature instability
• hypoglycaemia.
“These are usually mild and self-limiting, lasting just a few days, and no specific interventions other than reassurance are required,” Liz continues. “Very occasionally, babies may need additional support in NICU.”
The symptoms of NAS are not specific to that syndrome, but may instead be signs of other conditions or issues. The effects of maternal medicines is a diagnosis of exclusion.
IMPLICATIONS FOR PLACE OF BIRTH As midwives will be aware, women affected by mild mental health concerns are not excluded from birthing in primary settings, and allowing labour and birth to unfold physiologically is just as vital, if not more so, for women experiencing depression or anxiety during their pregnancy.
Liz is explicit in her recommendations surrounding place of birth. “Women with mild mental illness, on single antidepressants within usual dosages, and with an uncomplicated pregnancy, can birth at a primary birthing unit or at home, providing there is someone present who is trained in newborn life support and that oxygen and resuscitation equipment are available.”
“However, the LMC and the family need to be aware of the possibility of neonatal adaptation syndrome, which is usually mild and self-limiting. They should also be aware of the small risk of more rare and severe complications, such as persistent pulmonary hypertension of the newborn (PPHN), where the fetal circulation persists at birth.”
Identifiable by the presentation of cyanosis in the newborn, Liz states there is a small increased risk of PPHN with maternal antidepressants. Although observation of the newborn’s transition to extra-uterine life - including the establishment of respirations - is standard practice for midwives, Liz advises a higher level of vigilance in monitoring of the infant’s colour and respirations is warranted. If any concern, newborn resuscitation should be commenced, including use of pulse oximetry, and the neonatal team called.
And for those on a combination of medications or high doses, the message is clear. “If a woman is on a high SSRI dose and/or multiple medications or lithium/ mood stabilisers for her mental health, we would recommend that the mother gives birth in a maternity hospital facility that has paediatric support. The neonatal team should be involved, as there is a likelihood infant resuscitation will be required.”
Of note for midwives, both SSRIs and SNRIs may also increase the likelihood of postpartum haemorrhage (PPH), as shown by a systematic review and meta-analysis comprising eight studies and more than 40,000 PPH cases by Jiang et al. (2016). This may be worth factoring in to plans when discussing place of birth with women.
A summary table including commonly prescribed medications, their potential associated teratogenic risks, potential risks for exposed neonates and recommendations surrounding place of birth can be found in Table 1.
POSTPARTUM CONSIDERATIONS Liz advises that for the most part, women on antidepressants can continue on the same dose unchanged in the postpartum period, or if the dose has been increased in the third trimester, it may be possible to revert to the previous smaller dose. “Mental health in the postpartum period can be very variable,” she warns, adding, “some women are likely to need more care and will struggle, particularly if they are isolated or have few supports.”
She goes on to explain those with the highest risk are women with a diagnosis of bipolar disorder, particularly in the postpartum period, where they have up to a 50% risk of having a severe mood or psychotic episode. BREASTFEEDING Liz states nearly all of the commonly prescribed antidepressants are considered compatible with breastfeeding and transfer into breastmilk in low amounts. She explains some antidepressants, like fluoxetine, are worth being more cautious about, as they are secreted in breastmilk in higher amounts, and explains one group in particular - rarely prescribed now - called the monoamine oxidase inhibitors (MAOIs), are contraindicated due to a severe reaction people can have to particular foods whilst taking them.
Liz also highlights more vulnerable babies as a group to be aware of when considering implications for breastfeeding women taking antidepressants. “The other group that we have more concern for are very premature or unwell babies, who may have increased difficulty metabolising antidepressants or other medications, and may show adverse effects such as sedation or other signs of maladaptation, requiring extra monitoring.”
MIDWIFE’S ROLE So what should midwives do when a recommendation has been made for their client to continue or commence a medication for mental health needs, but the woman declines treatment? And at what point should a midwife refer a woman to her GP?
Liz empathises with women’s trepidations about taking medications in pregnancy. “This is always a difficult and understandable concern,” she says. “However, the evidence for adverse effects in the developing baby shows the risks are very low. This must be balanced against our increasing awareness of the potential impact that untreated depression/anxiety can have on the woman’s wellbeing and on the developing child in utero, or the adverse effect severe depression in the postpartum can have on the early mother-infant relationship and the developing child.”
Discussing all possible outcomes is paramount, as Liz reiterates. “Often, mothers tend to focus on their concerns regarding medications and can find it helpful to understand that untreated moderate to severe anxiety and depression can have risks as well.”
Naturally, the risks vary, depending on the severity of the mental health concern, and Liz acknowledges pharmacological management is not the only option. “Generally, antidepressants should only be prescribed for moderate to severe illness. Mild depression is better managed by general supportive measures or counselling.”
The onus is not on a midwife to make these decisions, but if a history of recent or current mental health medications is disclosed at booking, Liz recommends referring the woman for further advice. “Any woman on antidepressants who is planning to, or becomes pregnant, should be advised to have a consultation with her GP to discuss whether she should stay on medication and/or alter her dosage. Any woman with moderate to severe depression is likely to be advised to stay on medication during pregnancy, and it’s important that antidepressants are not stopped suddenly without this review, as it can lead to relapse of depression,” she cautions. Good communication between midwives and general practitioners around women’s mental health care during pregnancy will support the best possible outcomes.
Of course, a woman should definitely be referred to her GP if she thinks her depression and/or anxiety is worsening. “Urgent assessment (i.e. same day) is required if a woman has suicidal thoughts or thoughts of harm to her baby,” Liz states. “This could be at the GP or the local crisis mental health service.”
Triggers for relapse of mental illness or deterioration of mood will be well known to midwives, but Liz reiterates risk factors:
• History of mental health problems • History of trauma • Family history of postpartum mental illness (particularly in the pregnant woman’s mother) • Lack of social support at any time during the perinatal period • Having an unwell baby (either antenatally or postnatally) • Sleep deprivation • Overwhelm/exhaustion from over-exertion (particularly in postpartum - balancing visitors with rest/down time.
USEFUL RESOURCES FOR WOMEN For women seeking further information about the safety of medications in pregnancy, Nearly all of the commonly prescribed antidepressants are considered compatible with breastfeeding and transfer into breastmilk in low amounts.
Liz advises referring women to the UK Teratology Information Service’s website medicinesinpregnancy.org which contains comprehensive but easy to understand information leaflets for consumers.
Alternatively, she suggests encouraging women to call their local perinatal mental health service for phone advice. square
References available on request.
TABLE 1
DRUG CLASS MEDICATION
Selective serotonin reuptake inhibitor (SSRI) Sertraline
Citalopram
Escitalopram
Fluoxetine
Venlafaxine
Nortriptyline Very low levels preferred SSRI for breastfeeding
Slightly higher transfer than sertraline, but widely used
Dose of up to 20mg/day produces low levels in breast milk (not expected to cause adverse effects).
Secreted in breast milk in higher amounts (symptoms: colic, fussiness and drowsiness).
Detectable in breast milk: observe for symptoms of neonatal abstinence syndrome (NAS).
Low levels detected in breast milk
Serotonin noradrenaline reuptake inhibitor (SNRI)
POTENTIAL TERATOGENIC RISK: 1ST TRIMESTER USE
Very small increased risk (<1% of exposed infants) of cardiac malformations such as atrial sept defects and ventricular outflow tract obstruction with SRRIs, but most studies focus on paroxetine, so further research is needed.
Anencephaly, craniosynostosis, omphalocele and gastroschisis reported with SSRIs, but data is conflicting. Sertraline appears to cause the least placental exposure. (CDHB, 2017A)
No known teratogenic effects, however an effect similar to SSRIs cannot be excluded. (CDHB, 2017A)
No known teratogenic effects, however very few studies completed on TCAs. (UK Teratology Information Service [UKTIS], 2019).SSRIs cannot be excluded. (CDHB, 2017A)
RECOMMENDATION FOR PLACE OF BIRTH*
Safe to birth in primary setting if dose ≤100mg/day and no other psychotropic**
Safe to birth in primary setting if dose ≤20mg/day and no other psychotropic
Safe to birth in primary setting if dose ≤10mg/day and no other psychotropic
Safe to birth in primary setting if dose ≤20mg/day and no other psychotropic
Safe to birth in primary setting if dose ≤150mg/day and no other psychotropic
POTENTIAL RISKS FOR NEONATES
Evidence strongly suggests SSRI and/or venlafaxine use in late pregnancy can cause delayed neonatal adaptation syndrome (DNAS) in 15-30% of exposed neonates. Most commonly linked to fluoxetine, paroxetine and venlafaxine.
SSRI and/or venlafaxine use in late pregnancy have been shown to double risk of persistent pulmonary hypertension of the newborn (PPHN). Absolute risk appears small: two to three neonates per 1000. (CHDB, 2017A, 2017B)
SECRETED INTO BREAST MILK
(JONES, 2020)
Tricyclic (TCA) Safe to birth in primary setting if dose ≤150mg/day and no other psychotropic
*Standard doses of antidepressants have been provided by Dr Liz MacDonald, but no absolute guidelines exist. Higher doses could still be considered for primary birthing, however consultation with obstetric services in these situations is recommended. **Polypharmacy is a contraindication for birthing in a primary setting, as the risk of a newborn requiring resuscitation increases with exposure to more than one psychotropic medication in utero.
