As a general rule all drugs are best avoided in pregnancy unless essential, so as to minimise possible risk to the developing and newborn infant.
Lithium, valproate, carbamazepine, and lamotrigine should not normally be taken during pregnancy because of known risks to the developing infant. As asenapine is a new drug, there is very little evidence on its safety in pregnancy. Newborns who have been exposed to asenapine in the last three months of pregnancy show side effects in the first weeks of life, including agitation, abnormal muscle tone, tremor, extreme sleepiness, breathing problems, and difficulty feeding.
What are the risks of taking anticonvulsants during pregnancy?
NICE guidelines say, ‘Women with bipolar disorder who are considering pregnancy should normally be advised to stop taking valproate, carbamazepine, lithium and lamotrigine, and alternative prophylactic drugs (such as an antipsychotic) should be considered.’ The use of anticonvulsants in pregnancy is associated with children having developmental delay and needing special educational support.
The following problems are also recorded:
- Carbamazepine taken in the first three months of pregnancy increases the risk of spina bifida and related conditions; the risk may be reduced by taking folate supplements. In the last three months of pregnancy there is a risk of vitamin K deficiency in the infant, who should be monitored closely for signs of bleeding.
- Valproate should be avoided in pregnancy as it may cause defects and delay in development in the foetus. The possible harms include heart defects, spinal defects such as spina bifida, hare lip and cleft palate, malformed penis, and extra fingers or toes, as well as bleeding and liver disease in the newborn. The NICE guidelines on treatment of bipolar disorder state that valproate should not generally be given to women of child-bearing potential; if no effective alternative to valproate can be found, ‘adequate’ contraception should be used and women should be informed about the risk of harm to the foetus.
- Lamotrigine carries a risk of malformations, including cleft lip and palate.
NICE suggests that, during pregnancy, a low dose of antipsychotic is preferable to any of the anticonvulsants above or lithium, because they carry a smaller risk of harm to the foetus.
What are the risks of taking lithium during pregnancy?
Lithium may be taken during pregnancy providing it is done cautiously with awareness of the possible hazards, discussed below. For a few women, lithium maintenance treatment may be thought to be essential.
In the first three months of pregnancy there is some risk of malformation of the heart in the developing infant.
If lithium is given in late pregnancy there is risk of dangerous levels of lithium in mother and infant, as the way in which lithium is cleared from the body alters suddenly at childbirth. Lithium is also associated with a higher than expected frequency of stillbirths and deaths soon after birth.
If lithium is to be taken at any stage of pregnancy, careful monitoring of lithium levels is most important to avoid toxic effects.
If you are planning to get pregnant, it’s a good idea to discuss this with your doctor. If you decide to come off lithium, this should be done gradually over six to eight weeks, or longer, depending how long you have been taking it for. Afterwards it might be an idea to wait a few weeks before trying to conceive, in case your bipolar symptoms recur and you decide you need to go back on lithium.
If you find you are pregnant while you are taking lithium and it is early in pregnancy, you and your doctor might decide you should stop taking lithium immediately.
If you have been pregnant for some time without realising it, you should discuss with your doctor whether you should have an ultrasound scan. This can usually identify any possible problems in your baby’s development, looking especially at the heart.
Continuing lithium during pregnancy
If you and your doctor decide it’s best to continue with the lithium treatment, then you may need to adjust your dose. For example, the kidneys clear lithium from the body differently during pregnancy, so your dose may need to be increased to cope with this.
During the first half of pregnancy, blood lithium levels should be checked monthly; towards the end this should be done weekly. It may also be better to split the total daily dose into three or more doses a day, so that the level of lithium in your blood does not reach such high peaks as it does if you take larger doses less often.
In late pregnancy it is very important that the doctor who is prescribing and monitoring your lithium treatment consults closely with the obstetrician responsible for your baby’s delivery.
Lithium and childbirth
In childbirth, the way that the body clears lithium alters suddenly. If you have continued taking lithium during pregnancy, some doctors may suggest you withdraw lithium treatment gradually in the weeks leading up to the estimated date of delivery, in order to minimise the risk of toxic effects in both you and the child.
Others may suggest continuing with lithium treatment until the date the baby is due or until labour begins. They may think you should continue with lithium as long as possible as a protective factor against the risk of serious mental illness (postnatal psychosis).
Lithium should be stopped as soon as labour begins. The obstetrician will need to carefully check your fluid and salt balance and the level of lithium in the blood.
For those who have already had a bipolar episode there is a significant risk of serious mental illness (puerperal psychosis) during the weeks after the birth. Because of this, lithium is often started again as a preventive measure a few days after childbirth. Frequent monitoring of the level of lithium in the blood will be needed at this time to achieve a therapeutic dose. Continuing use of the drug would need to be reviewed in the normal way at the end of the period of risk.
Are there alternatives to taking lithium during pregnancy?
If drug treatment is considered to be essential, then antidepressants or antipsychotic drugs may be prescribed instead. The type of drug given would depend on the pattern of your mood changes and your symptoms. The following information indicates particular risk periods associated with these alternative drugs.
Tricyclic antidepressants given in late pregnancy have been associated with withdrawal symptoms in newborn babies. Irritability, muscle spasms, restlessness, sleeplessness, fever and fits have been reported.
One antipsychotic drug, prochlorperazine (Stemetil), is associated with malformations in the developing baby when given during the first three months of pregnancy. The use of antipsychotic drugs in late pregnancy may cause temporary reactions in newborn infants: Parkinson’s reactions have occasionally been reported. These include muscular rigidity, involuntary movements and shaking. If long-acting drugs are taken they take time to clear from the body. The last dose should be taken six to eight weeks before the expected birth.
You should be able to get further information from your doctor regarding any drug you are advised to take during pregnancy. It is very important to discuss all aspects of your drug treatment and any concerns you may have with your doctor, obstetrician, midwife and pharmacist.
What are the risks of taking mood stabilisers while breastfeeding?
You should not breastfeed while taking lithium, as lithium passes into the breast milk in sufficient amounts to be dangerous to the baby.
Carbamazepine, valproate and lamotrigine all appear in breast milk in small amounts so breastfeeding is not recommended. However the British National Formulary suggests that amounts are not considered sufficient to be harmful.
You should not breastfeed while taking asenapine.
Children and mood stabilisers
The ‘British National Formulary (BNF)’ and the ‘Summaries of Product Characteristics‘(produced by the drug manufacturers) say that lithium is not suitable for children. However, the ‘BNF for children’ states that lithium may be given to children, only on the advice of a specialist. Because of the long-term effects, the need for treatment should be reviewed regularly.
The ‘BNF for children’says that carbamazepine and valproate may be useful in children unresponsive to lithium. It gives no guidance on the use of lamotrigine as a mood stabiliser in children.
Asenapine is not recommended for anyone below the age of 18.
All drugs should be used with caution, and at doses appropriate to the child’s age and size.