Pregnancy and bipolar affective disorder drugs

Lithium in pregnancy (1):

• lithium is teratogen - increases the incidence of Ebstein's anomaly by a factor of 10 to 1:2000 births.
• increased associated miscarriage risk with lithium treatment during pregnancy.
• reported rate of major congenital malformations is around 4-12% in babies exposed in utero to lithium

Other drugs used in the management of bipolar affective disorder and there incidence of major congenital malformatons if used in pregnancy are (2):

• 5-6% in valproate-exposed babies have major congenital malformations (2)
  • medicines containing valproate taken in pregnancy can cause malformations in 11% of babies and developmental disorders in 30-40% of children after birth (4)
• 2.3-5.3% in carbamazepine-exposed babies have major congenital malformations (2)
  • compares with a rate of 2.4-4.5% in the general population

The period of highest risk for organ malformation is the first 8 weeks of pregnancy

Any female of child-bearing potential should receive appropriate advice about contraception

• she should be encouraged to plan her pregnancies and should be advised carefully about the benefits and risks of the various treatment options open to her should she decide to try to become pregnant
  • options may include gradual discontinuation of some or all medication before conception, or switching to agents with lower risk to the fetus, or continuing with existing treatment
  • she will also need advice about antenatal diagnosis of fetal abnormality if she decides to remain on drug treatment
  • physiological changes during the pregnancy may necessitate dose adjustment to ensure that therapeutic serum concentrations are maintained

All drugs used in the treatment of bipolar disorder are secreted in breast milk in varying degrees, but the risks to the newborn baby are uncertain (2)

Breastfeeding and lithium

• WHO guidance (5) with respect to lithium and maternal breastfeeding stated:
  • avoid if possible. Monitor the infant for side-effects(restlessness or weakness). Monitor lithium levels inmother’s blood
• NICE stated (3)
  • lithium should not be routinely prescribed for women, during breastfeeding (because of the high levels in breast milk)
• NHS Specialist Pharmacy Service state (6):
  • lithium can also be used for the management of bipolar disorder, but must be with extreme caution, under specialist supervision, and with strict infant monitoring conditions.

NICE have stated

• with respect to lithium that (3):
  • do not offer lithium to women who are planning a pregnancy or pregnant, unless antipsychotic medication has not been effective
  • if antipsychotic medication has not been effective and lithium is offered to a woman who is planning a pregnancy or pregnant, ensure:
    • the woman knows that there is a risk of fetal heart malformations when lithium is taken in the first trimester, but the size of the risk is uncertain
    • the woman knows that lithium levels may be high in breast milk with a risk of toxicity for the baby
    • lithium levels are monitored more frequently throughout pregnancy and the postnatal period
  • if a woman taking lithium becomes pregnant, consider stopping the drug gradually over 4 weeks if she is well. Explain to her that:
    • stopping medication may not remove the risk of fetal heart malformations
    • there is a risk of relapse, particularly in the postnatal period, if she has bipolar disorder
  • if a woman taking lithium becomes pregnant and is not well or is at high risk of relapse, consider:
    • switching gradually to an antipsychotic or
    • stopping lithium and restarting it in the second trimester (if the woman is not planning to breastfeed and her symptoms have responded better to lithium than to other drugs in the past) or
    • continuing with lithium if she is at high risk of relapse and an antipsychotic is unlikely to be effective
  • if a woman continues taking lithium during pregnancy:
    • check plasma lithium levels every 4 weeks, then weekly from the 36th week
    • adjust the dose to keep plasma lithium levels in the woman's therapeutic range
    • ensure the woman maintains an adequate fluid balance
    • ensure the woma gives birth in hospital
    • ensure monitoring by the obstetric team when labour starts, including checking plasma lithium levels and fluid balance because of the risk of dehydration and lithium toxicity
    • stop lithium during labour and check plasma lithium levels 12 hours after her last dose
      
      
  • valproate in women of childbearing potential (4)
• do not offer valproate to women of childbearing potential for long-term treatment or to treat an acute episode
• if a woman of childbearing potential is already taking valproate, advise her to gradually stop the drug because of the risk of fetal malformations and adverse neurodevelopmental outcomes after any exposure in pregnancy
• valproate must not be used in pregnancy, and only used in girls and women when there is no alternative and a pregnancy prevention plan is in place. This is because of the risk of malformations and developmental abnormalities in the baby
• MHRA's latest advice and resources on sodium valproate. Medicines containing valproate taken in pregnancy can cause malformations in 11% of babies and developmental disorders in 30-40% of children after birth. Valproate treatment must not be used in girls and women including in young girls below the age of puberty, unless alternative treatments are not suitable and unless the terms of the pregnancy prevention programme are met. This programme includes: assessment of patients for the potential of becoming pregnant; pregnancy tests; counselling patients about the risks of valproate treatment; explaining the need for effective contraception throughout treatment; regular (at least annual) reviews of treatment by a specialist, and completion of a risk acknowledgement form

Reference:

1. Update 1998;57 (7): 622-627.
2. Drug and Therapeutics Bulletin 2005; 43 (5): 33-36.
3. NICE (2020). Antenatal and postnatal mental health
4. NICE (April 2018). Bipolar disorder.
5. World Health Organization (WHO) 2002. Breastfeeding and maternal medication. Recommendation for drugs in the eleventh WHO model list of essential drugs
6. NHS Specialist Pharmacy Service (October 2023). Treating bipolar disorder during breastfeeding