After studying this chapter you should be able to:
Knowledge criteria
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Demonstrate an understanding of the common antenatal and postnatal psychiatric illnesses and their management
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Discuss the aetiology and incidence of postpartum mood disorders
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Describe the presentation and diagnosis of the common clinical syndromes
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Contrast the clinical features of normal postnatal mood changes (the ‘blues’) with pathological mood disorders
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List the strategies for prevention and management of mental illness in pregnancy
Clinical competencies
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Assess the risk of mental illness in pregnancy and the puerperium
Professional skills and attitudes
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Consider the issues of psychiatric medication and breast feeding
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Consider the impact of psychiatric illness in pregnancy on the community, family and child
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Reflect on the causes of maternal death in women with psychiatric disorders in pregnancy
Introduction
The relevance of maternal mental health to obstetricians
Psychiatric disorder is a leading cause of maternal morbidity and mortality, contributing up to 25% of maternal deaths in pregnancy and the year postpartum in the UK and other developed nations.
Childbirth is a substantial risk to mental health, greater than at other times in a woman’s life. There is an elevated incidence of severe mood (affective) disorders postpartum associated with an increased risk of suicide in the early postpartum weeks ( Box 14.1 ).
Women with a previous serious affective disorder, even if well during pregnancy and for many years, are at 50% risk of recurrence in the early postpartum weeks.
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15% ‘depression’
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10% major depressive illness
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4/1000 admitted
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2/1000 psychosis
A substantial proportion of women seen by maternity services will have mental health problems. A significant, although smaller number, will be well but have risk factors for serious postpartum illness that will need to be proactively managed.
There are effective treatments for serious mental illness and the prognosis for postpartum onset affective disorder is good. However, if untreated or with delays in detection, morbidity may be prolonged with adverse effects on the family life and infant.
Perinatal psychiatry
Perinatal psychiatry is the internationally recognized term for psychiatric disorders that complicate pregnancy, childbirth and the postpartum period.
Perinatal psychiatric disorders include:
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New onset conditions in previously well women.
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The recurrence of conditions in women who have been well for some time but have a history of a previous illness.
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Relapses or deteriorations in women who are currently ill or who have not fully recovered from a previous illness.
Specialized perinatal psychiatric services are organized to meet the special needs of women and work in close relationship with maternity services.
Antenatal psychiatric disorders
Antenatal psychiatric disorders are common, affecting between 15 and 20% of pregnancies. In early pregnancy the rate and range of psychiatric disorder will be the same as in the non-pregnant population of the same age. Maternity services will therefore see women with learning disability, substance misuse, schizophrenia, bipolar disorder, depressive illness, obsessional compulsive disorder and anxiety states; these women are likely to be receiving medication. Enquiries should be made in early pregnancy about previous psychiatric history and current mental health and medication.
The incidence of psychiatric disorder during pregnancy is slightly increased, due to an increase in the rates of anxiety and depression. The incidence of serious mental illness is much reduced in pregnancy, in marked contrast to the postpartum period.
Mild to moderate psychiatric disorder
Mild to moderate depressive illness and anxiety states occur in about 15% of pregnancies.
The incidence and prevalence is highest in the first trimester of pregnancy and decreases in later pregnancy. However, if present in later pregnancy they may persist and worsen in the postpartum period.
They may be related to social circumstances or concerns about the pregnancy. The woman may have been depressed before pregnancy. Stopping antidepressants in early pregnancy carries a substantial risk of relapse: at least 50%.
Anxiety is a prominent feature of antenatal depressive illness. There is some evidence that significant anxiety in pregnancy is linked to early delivery, postnatal depressive illness and problems with infant development.
Management
Many women with milder depression and anxiety in early pregnancy will improve as the pregnancy progresses. However, some will not and will require intervention. Psychological treatments such as guided self-help, counselling and cognitive behavioural therapy are more effective for mild to moderate depression and anxiety than antidepressant drugs. Together with concerns about the effects in pregnancy, it is recommended that antidepressants are not prescribed for new onset mild to moderate antenatal depressive illness and anxiety states. Initially there should be a period of ‘watchful waiting’ for 2 weeks. If symptoms persist, the woman should be referred for psychosocial treatments, arranged in collaboration with the woman’s general practitioner and community midwife.
A common problem for obstetricians and general practitioners is a relapse of depression or anxiety after a recent illness or stopping antidepressants. The most commonly used antidepressants are SSRIs, e.g. fluoxetine. Suddenly stopping antidepressants may result in severe anxiety and panic attacks and later a recurrence of a depressive illness. The woman is likely to be very distressed, concerned about continuing her medication because of effects on the pregnancy but also frightened of stopping. Although there are concerns about SSRIs the absolute risk is small. For these women the least detrimental alternative may be to restart their medication and slowly withdraw over a longer period of time, whilst arranging for psychological treatments. Some women will need to continue their antidepressant medication.
Serious mental illness
The incidence of schizophrenia, episodic psychoses and bipolar disorder is lower during pregnancy than at other times. This is in marked contrast to the postpartum period where the incidence of serious affective illness is markedly elevated. However, the prevalence of these conditions during pregnancy will be the same as in women of the same age.
A woman who has fully recovered from an episode more than 2 years ago and is not receiving treatment is probably not at increased risk of an antenatal recurrence. However, there is a 50% risk of an early onset postpartum recurrence. It is essential that a previous history, even if she has been well for many years, is followed by a referral to psychiatric services during pregnancy and a peripartum management plan developed.
However, if she had an illness within 2 years of conception, is currently unwell or is maintained on medication, the risk of antenatal relapse, particularly if her medication has been stopped, is considerable.
Psychosis during pregnancy is a psychiatric emergency and can severely compromise maternal and fetal health. Concerns about the possible adverse effects of medication on the developing fetus have to be balanced against the risks of maternal relapse that can compromise fetal wellbeing.
Management
Women who experienced a serious mental illness more than 2 years ago and who are currently well should be recognized as being at a high risk of a postpartum illness. There should be a peripartum management plan that involves advising the woman, her family and health professionals of the early signs of recurrence, and a system of close monitoring for the first 6 weeks following delivery. Consider the involvement of a consultant obstetrician in her antenatal care, but otherwise there are no special steps to be taken during pregnancy.
Women who have had a recent serious mental illness or are taking maintenance medication are at high risk of both antenatal and postpartum relapse. The risk of antenatal relapse is greatest later in the second half of pregnancy. They should be managed jointly by maternity and psychiatric services with consultant obstetrician involvement. Ideally they should have received advice about the advisability of a pregnancy and the choice of medication. However, in the real world, half of pregnancies are unplanned. They may present in early pregnancy taking their usual medication. Of particular concern to obstetricians are antipsychotic agents and mood stabilizers.
There is little evidence of the effects in pregnancy of the newer most commonly used ‘atypical’ antipsychotic drugs such as olanzapine and risperidone. However, the absolute risk of adverse effects is likely to be small. This should be balanced against the high risk of a relapse if the antipsychotic agent is reduced or withdrawn. In general, antipsychotic medication should be continued during pregnancy. Obstetric involvement is required with particular attention to the probable increased risk of gestational diabetes and venous embolism.
Mood stabilizers, used for the control and maintenance of bipolar disorder, present a different problem. Wherever possible they should be withdrawn before conception and, if necessary, substituted by an antipsychotic agent.
Antiepileptic drugs, particularly valproate, are increasingly used as mood stabilizers in bipolar disorder. They are teratogenic and associated with both structural and functional neurodevelopmental problems. The dose should be immediately reduced, slowly withdrawn and an effective substitute sought.
A relapse or acute recurrence during pregnancy is an urgent situation and senior psychiatric involvement should be sought, preferably from a specialist in perinatal psychiatry. If psychiatric admission is necessary in the last trimester of pregnancy, it should be to a specialized mother and baby unit.
Psychiatric medication in pregnancy
At least 10% of women will be taking psychiatric medication at the beginning of pregnancy, usually antidepressants but sometimes an antipsychotic or mood stabilizer.
With the exception of mood stabilizers, the evidence for adverse effects of antidepressants and antipsychotics is emerging and conflicting. It is likely that the absolute risks are small and need to be balanced against the established risks of stopping maternal medication and the effects of relapse on maternal and fetal health.
It is not possible to give a definitive list of psychiatric drugs that are ‘safe’ and ‘unsafe’. The reader should always check the latest systematic reviews before giving advice or initiating a prescription.
Antidepressant medication
Monoamine oxidase inhibitors (MAOIs)
These are now rarely used. They should not be used in pregnancy because of the risks of interaction with certain food stuffs and analgesics.
Tricyclic antidepressants (TCAs)
These have been in use for 40 years. They include amitriptyline, imipramine, clomipramine and doxepin (dothiepin). The usual therapeutic dose is 150 mg daily, and tablet size allows for adjusting dosage by 25 mg increments. With the exception of clomipramine, there is no evidence that TCAs are associated with an increased risk of structural or functional fetal abnormalities, early pregnancy loss, restricted interuterine growth or early delivery.
Clomipramine may be associated with the same increased risk of cardiac abnormalities as SSRIs and should be used with caution in pregnancy.
TCAs, if taken at full dose prior to delivery, can cause neonatal withdrawal effects. These include jitteriness, convulsions (rarely), hypoglycaemia, hypothermia and problems feeding. These effects, however, are short-lived.
Many practitioners would consider reducing the dose of TCAs prior to delivery. However, for women who are seriously depressed a reduction may result in a relapse. In such circumstances a managed delivery at or shortly before term should be considered.
Current guidelines support the use of TCAs in pregnancy
If antidepressants are indicated in pregnancy because of a profound depressive illness with the characteristic ‘biological’ symptoms, then a suggested regime would be 50 mg of imipramine or amitriptyline increasing by 25 mg every few days until a therapeutic dose of 150 mg is reached.
Side-effects of TCAs include dry mouth, blurred vision and sometimes difficulty passing urine. TCAs, particularly dothiepin, are cardiotoxic in overdose. TCAs should not be prescribed if there is a risk of suicide.
Selective serotonin reuptake inhibitors (SSRIs)
These are the most frequently prescribed antidepressants. They include fluoxetine, paroxetine, sertraline and citalopram.
SSRIs, particularly paroxetine, have been linked with cardiac abnormalities, specifically ventricular septal defect. The evidence is emerging and conflicting, but specific concerns have led the drug administrations in the UK and US to advise against the use of paroxetine in pregnancy. SSRIs as a class may be associated with increased rates of early pregnancy loss, growth restriction, early delivery and pulmonary hypertension in the newborn.
The evidence of neonatal compromise when taking an SSRI prior to delivery is more robust. Preterm babies are particularly vulnerable. Neonatal compromise includes difficulties in feeding, hypoglycaemia and hypothermia. However, these are temporary.
Despite the likely increase in the relative risk of these effects, the absolute risk is low (with the exception of neonatal compromise).
Current guidelines support the use of fluoxetine and sertraline in pregnancy
Some clinicians would advise the withdrawal of SSRIs prior to delivery. However, this may compromise the management of severely depressed women when a managed delivery may be considered and a watchful eye kept on the neonate.
Serotonin–norepinephrine reuptake inhibitors (SNRIs)
The lack of evidence of their safety and concerns about pulmonary hypertension suggest that these antidepressants should not be used in pregnancy.
Antipsychotic medication
There are two broad groups, the older ‘typical’ antipsychotics such as chlorpromazine, trifluoperazine and haloperidol, and depot long-lasting antipsychotics such as Modecate® and the newer ‘atypical’ antipsychotics such as olanzapine, quetiapine and risperidone. These drugs are used to treat and maintain schizophrenia, episodic psychoses and bipolar illness. Stopping them leads to a marked elevation in the risk of relapse in the next 6 months. Both groups of antipsychotics are equally effective but differ in their side-effects and acceptability.
Older ‘typical’ antipsychotics
These have been in use for 40 years. There is no evidence that they are linked with fetal abnormality or early pregnancy loss. However, schizophrenia, an indication for their use, is associated with poor obstetric outcome, including early delivery, increased rates of caesarean section, maternal and neonatal mortality, and neurodevelopmental problems.
Anticholinergic drugs used to counteract the extra pyramidal side-effects of typical antipsychotics cannot be regularly used in pregnancy.
Postural hypotension, particularly with chlorpromazine can cause falls and theoretically compromise placental function.
If well maintained on typical antipsychotic agents, they should not be changed during pregnancy. However, a watchful eye should be kept on the neonate for withdrawal symptoms to the sedative effective of maternal medication.
Current advice is that typical antipsychotic drugs may be used during pregnancy. However, depot injections such as Modecate should be avoided because of difficulties adjusting the dose.
Newer ‘atypical’ antipsychotics
There is less evidence about their effects in pregnancy than the older typical antipsychotics. There is no evidence to suggest an association with structural or functional fetal abnormality. The risk of maternal relapse if they are stopped is substantial.
There is consistent evidence linking atypical antipsychotic agents, particularly olanzapine, with gestational diabetes and rapid, substantial weight gain. There are also concerns of increased risk of venous embolism. Women on atypical antipsychotics should be closely monitored by an obstetrician. A watchful eye needs to be kept on the neonate for potential withdrawal symptoms from the sedative effect of maternal medication.
Current guidelines advise that atypical antipsychotics may be used during pregnancy. Clozapine is the exception. It is used to treat refractory schizophrenia and should not be used in pregnancy.
The adverse effects of all antipsychotics are dose related. The lowest effective dose should therefore be given. Maintaining medication will lower the risk of relapse and avoid having to use much higher doses in an acute crisis.
Mood stabilizers
Lithium carbonate and anti-epileptic drugs (AEDs) mainly sodium valproate and valproate semisodium (Depakote®) are used to treat and maintain women with bipolar disorder.
Lithium is associated with an increased risk of cardiac abnormalities of all types; the risk is 1 in 10 in exposed pregnancies. It is specifically linked to a marked increased risk of Ebstein’s anomaly. However, the absolute risk of this rare abnormality is low. Ideally women taking lithium should receive advice about the risks to their mental health due to pregnancy and the effects of lithium withdrawal that should occur before conception. If a woman becomes pregnant whilst taking lithium the following guidelines should be followed.
If she has been well for over 2 years the lithium should be slowly withdrawn under psychiatric supervision by 200 mg every 2 weeks. She will require close monitoring for any evidence of a relapse when an antipsychotic agent should be used.
If she has been recently ill or has relapsed after previous withdrawal of lithium, then continuation of the lithium may be the least detrimental alternative at the lowest dose to maintain an effective serum level.
A level three ultrasound scan should be arranged at 22–24 weeks to look for fetal cardiac abnormalities.
Theoretically, lithium can be used in the second trimester of pregnancy. However, its use in later pregnancy is problematic. Maternal serum levels will fall but the fetal level will equilibrate and fetal clearance of lithium is less than the mother’s. Lithium in later pregnancy is associated with fetal hypothyroidism and polyhydramnios. During delivery, with physiological diuresis, maternal serum lithium levels may suddenly rise to toxic levels and there may be neonatal lithium toxicity. Using lithium in pregnancy is a high-risk strategy requiring close collaboration between the obstetrician and psychiatrist. Serum lithium levels need to be checked weekly in the last trimester. The woman should be induced before term to allow for the lithium to be stopped 10 days prior to delivery. If a woman starts labour whilst taking lithium it should be immediately stopped, hydration and diuresis maintained and intravenous access obtained. The neonatal paediatrician should be alerted.
Anti-epileptic drugs
All AEDs (the possible exception of lamotrigine) are associated with an elevation in the risk of fetal malformations in general and neural tube defects in particular. The risk with sodium valproate is higher than for other AEDs, particularly for neural tube defects, neurodevelopmental delay and impaired cognitive functioning in school age children. Between 8% and 15% of all exposed pregnancies are affected, depending on dosage and polypharmacy.
Sodium valproate and valproate semisodium (Depakote) are widely used as mood stabilizers. It is no longer thought that epilepsy itself is responsible for these increased risks, and it is now accepted that anticonvulsants are responsible. Valproate used for psychiatric reasons will have the same risks.
Current guidelines on the management of epilepsy, bipolar illness and antenatal mental health advise that valproate should not be used in women of reproductive age unless there are no effective alternatives.
If a woman becomes pregnant whilst taking valproate, the following guidelines should be observed. She should be urgently reviewed by both a consultant obstetrician and psychiatrist and collaboratively managed.
The dose should be reduced to 800 mg daily or less. Daily dosage of long-acting preparations should be converted to a twice or thrice daily regime to minimize ‘pulsing’ of the fetus. The earliest anomaly scan should be arranged and the ultrasonographer warned of the fetal exposure. Valproate should be slowly withdrawn, e.g. by 200 mg every 2 weeks, and if necessary replaced by an antipsychotic drug.
Careful monitoring is required because of the possibility of a relapse.
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