Mental health problems in pregnancy

Risk factors for perinatal depression

• High correlation with increased risk
  • Depression in pregnancy
  • Past history of affective disorder
  • Family history of affective disorder
  • Lack of support – partner, mother
  • Multiple stressors
• Some correlation with increased risk
  • Perfectionistic personality
  • Low socioeconomic status
  • Aboriginal and Torres Strait Islander people
  • Childhood abuse

• A high score on an Edinburgh Postnatal Depression Scale does not mean that the woman has a psychiatric illness. Nor does it mean, even if it is recommended, that she will present for treatment. 
• It does, however, raise a possibility that she might benefit from help. 
• The stigma of depression, as well as being labelled a failure and a bad mother, are still strong disincentives for women to acknowledge that they might be at risk or need help. 
• Although awareness campaigns help, some women still struggle to recognise that they might be depressed, particularly when the pregnancy has been planned and the baby is wanted and loved.
• Aversion to taking medication, especially when pregnant or breastfeeding, adds to the reluctance to seek help. Part of this is fear based on lack of knowledge, but these women ask to be listened to first, and a too rapid resort to a prescription is likely to disrupt or rupture the therapeutic alliance.
• Education and implementation of social supports may be better first steps and medication reserved as a next-step option, allowing women to reflect and ask questions before committing to drug treatment. 
• For some women, it is a baby-related crisis that gets them attention; when the baby is deemed well, then the focus can turn to how the mother is coping.
• When to consider use of antidepressants for perinatal depression
  • Severe or significant number of symptoms, particularly biological symptoms (e.g. sleep and appetite disturbance)
  • Persistent symptoms
  • Response to psychosocial management nil or inadequate
  • Unable to offer psychosocial management because of cost, distance, or other practical factors
  • Family or past history of good response to medication
  • Woman’s preference

Antidepressant use during pregnancy

b

Potential benefits and harms to the patient and fetus associated with psychotropic use during pregnancy

[NB1] [NB2]

	Fetus	Patient
Potential harms of psychotropic use	miscarriagefetal death in utero stillbirthpreterm birthcongenital abnormality [NB3]growth restrictionpoor neonatal adaptationlong-term neurodevelopmental effects [NB4]	stress and worry about potential for harms from drug exposure
Potential benefits of psychotropic use	reduced:abuse and neglectadverse outcomes from an active psychiatric disorder during pregnancy [NB5]	reduced:relapse of psychiatric disordersuicideself-harmrelationship deteriorationuse of harmful substitutes (eg alcohol)
NB1: See the relevant drug monograph for additional information on potential harms.NB2: Data on potential fetal harms caused by psychotropics are often confounded by the underlying disorder—see Overview of psychotropic pregnancy data.NB3: The background rate of congenital malformations in the general population is approximately 3%.NB4: Long-term neurodevelopmental effects of psychotropic exposure during pregnancy remain largely unexplored.NB5: Adverse outcomes from an active psychiatric disorder during pregnancy include preterm labour, low birth weight and poor neonatal vital signs.

Considerations for antidepressant use in pregnancy

If an antidepressant is required during pregnancy, consider the:

• principles of psychotropic use during pregnancy
• amount of data on the antidepressant (see below)
• risk of teratogenicity, miscarriage and preterm birth, poor neonatal adaptation, persistent pulmonary hypertension of the neonate and neurodevelopmental disorders
• patient’s risk of gestational hypertension, postpartum haemorrhage—low-quality data have associated antidepressant use during pregnancy with an increased risk of gestational hypertension and postpartum haemorrhage.

Antidepressant safety data in pregnancy are limited—selective serotonin reuptake inhibitors (SSRIs) have the largest amount of pregnancy safety data of all antidepressants.

If an antidepressant is required for the first time during pregnancy, use an SSRI other than paroxetine because of its association with cardiac malformations and miscarriage. Sertraline is most commonly used because it has the most safety data. If the patient intends to breastfeed, avoid starting fluoxetine during pregnancy because, of the SSRIs, it has the highest reported concentrations in breastmilk.

If a patient is already taking paroxetine or fluoxetine, the evidence of harm is not sufficiently strong to warrant switching to a different SSRI. Discuss the concerns so that the patient can make an informed decision about treatment—see Principles of psychotropic use during pregnancy.

Although less data are available to support its use in pregnancy, venlafaxine appears to have a similar risk profile to SSRIs in terms of teratogenicity and poor neonatal adaptation. The risk of miscarriage is similar to that of paroxetine.

Very limited data suggest use of mirtazapine or a tricyclic antidepressant (TCA) is not associated with congenital malformations. Cases of neonatal adaptation problems have been reported.

The safety during pregnancy of agomelatine, desvenlafaxine, duloxetine, mianserin, moclobemide, phenelzine, reboxetine, tranylcypromine and vortioxetine has not been adequately studied. Only continue or start these drugs in pregnancy if the harm–benefit analysis supports it.

The association of antidepressant use with low birth weight/small-for-gestational age infants is controversial. Studies do not adequately control for depression, which has been shown to contribute to low birth weight/small-for-gestational-age infants.

If a decision is made to switch or stop the antidepressant, see Switching antidepressants or Stopping an antidepressant.

Teratogenicity

Early data suggested an increase in the risk of some rare malformations, particularly cardiac, with SSRI and SNRI exposure. However, the association has not been consistently confirmed in meta-analyses and may be explained by confounders (eg depression, increased cardiac surveillance with gestational exposure). A cautious interpretation is that gestational exposure may slightly increase the risk of cardiac malformations; paroxetine has most often been implicated. However, do not avoid using an SSRI or SNRI if indicated during pregnancy—see Principles of psychotropic use during pregnancy and Considerations for antidepressant use in pregnancy.

TCAs and mirtazapine have not been associated with malformations but have not been studied to the same extent as SSRIs and SNRIs, so are not thought to be safer and should be used with caution. Agomelatine, mianserin, moclobemide, phenelzine, reboxetine, tranylcypromine and vortioxetine have not adequately studied during pregnancy; use with extreme caution.

Miscarriage and preterm birth

Although some data suggest a link between all antidepressants and miscarriage and preterm birth, this association is inconsistent and subject to confounding. SSRIs and SNRIs are the antidepressants most frequently studied in pregnancy; a small but consistent association has seen between:

• paroxetine and venlafaxine and a higher risk of miscarriage,
• SSRI and SNRI use in late pregnancy and a higher risk of preterm birth.

In patients who have risk factors for hypertension or postpartum haemorrhage, or have a history of miscarriages or preterm birth of unknown aetiology, use an antidepressant with extra caution. If an antidepressant is required, it is suggested, on limited evidence, to avoid paroxetine and venlafaxine.

Abruptly stopping clomipramine during pregnancy has been associated with premature birth and neonatal seizures.

Consider the above advice in accordance with Principles of psychotropic use during pregnancy and Considerations for antidepressant use in pregnancy.

Poor neonatal adaptation

Poor neonatal adaptation is observed in approximately 10 to 30% of neonates exposed to an SSRI in late pregnancy and has also been observed with other antidepressants. It is a syndrome resembling serotonergic overstimulation in the first few days of life. Neonatal adaptation syndrome increases the likelihood of admission to a neonatal unit and is characterised by:

• central nervous system reactivity (irritability, restlessness, tremor, hyperreflexia, myoclonus and, occasionally, seizures)
• gastrointestinal disturbance (eg feeding difficulties)
• respiratory difficulties
• low Apgar scores.

Do not stop or reduce the dose of an antidepressant in the last few weeks of pregnancy with the aim of avoiding neonatal adaptation syndrome; it does not improve neonatal outcomes and increases the risk of patient relapse.

In most cases, if the infant receives supportive care, the syndrome subsides within 2 weeks.

Consider the above advice in accordance with Principles of psychotropic use during pregnancy and Considerations for antidepressant use in pregnancy.

Persistent pulmonary hypertension of the neonate

Persistent pulmonary hypertension of the neonate (PPHN) is a rare condition affecting 1 to 2 infants per 1000 live births. It has a high rate of mortality (5%) and severe morbidity (60%). Although fetal exposure to an SSRI after 20 weeks gestation is associated with a small increase in absolute risk of this syndrome, the risk is still extremely low and does not preclude the use of SSRIs in pregnancy. The association does not appear to apply to other antidepressants, though these have been used in much smaller numbers than SSRIs, making it less likely that an association with such a rare disorder would be detectable. Advise the patient of this small increase in risk as part of the treatment decision-making process—see Principles of psychotropic use during pregnancy and Considerations for antidepressant use in pregnancy.

Neurodevelopmental disorders in older children

At the time of writing, there is no conclusive evidence of a causal link between antenatal SSRI use and neurodevelopmental disorders in later life, including autism spectrum disorder and attention deficit hyperactivity disorder (ADHD). Any association is likely to be accounted for by confounders rather than gestational SSRI exposure.

Other antidepressants have not been studied for such an association.