Pregnancy And Mood Stabilizers: Safe Options For Mothers-To-Be

Mood stabilizers are used to treat bipolar disorder, a severe mood disorder with an episodic course with varying intervals of remission lasting months or years. The typical age of onset for bipolar disorder is in the early twenties, which leads to substantial overlap with periods of pregnancy and childbirth in affected women.

Pregnancy is not protective against the relapse of bipolar disorder and the postpartum risk increases further. Therefore, it is important to consider the safety of mood stabilizers during pregnancy.

The safety of mood stabilizers needs to be considered in terms of associated teratogenicity, poor neonatal adaptation, and long-term neurobehavioral sequelae.

Lithium, which is used to treat bipolar disorder, has been associated with an increased risk of congenital anomaly and cardiac malformations. However, the absolute risk is small (0.05-0.1%) and lithium is considered to be the safest mood stabilizer for use during pregnancy.

Valproic acid or its preparations, especially in the first trimester, are associated with a markedly high rate of multiple congenital malformations and several-fold higher risk for neural tube defects. Valproic acid has been significantly associated with adverse neurodevelopmental outcomes, including an increased risk of developing autism spectrum disorder.

Carbamazepine exposure during pregnancy might also cause Vitamin K deficiency in neonates, leading to an increased risk of bleeding diathesis in neonates.

Lamotrigine has a relatively favorable reproductive safety profile, with a low risk of congenital malformations.

Most second-generation antipsychotics, such as olanzapine, quetiapine, or aripiprazole, appear to be relatively safe during pregnancy.

Selective serotonin reuptake inhibitors, a class of antidepressants, have been associated with a small but significant increase in the risk of fetal cardiac malformations.

Overall, the choice of mood stabilizer during pregnancy should be made on a case-by-case basis, weighing the risks and benefits of each medication.

Lithium during pregnancy and breastfeeding

Lithium is a medication used to treat bipolar disorder and prevent major mood swings. It can also be used to boost the effect of antidepressants when depression does not respond to treatment with an antidepressant alone.

Pregnancy

Pregnancy means that women will have to think about whether to continue, stop, or change any medication they are taking, including lithium. Decisions about medications in pregnancy are not easy. This is because there is often not enough information to say that a medication is 100% safe for use in pregnancy. It is important to weigh up the risks and benefits of taking medication in an individual case.

If a woman wishes to get pregnant and is taking lithium, she should talk to her psychiatrist or GP. If there is a perinatal psychiatrist in the area, the woman should be referred to them. A psychiatrist can help decide whether it is best to continue lithium treatment, or to consider changing to another medication.

If a woman is taking lithium and finds out she is pregnant, she should talk to her psychiatrist or GP as soon as possible. The psychiatrist can help make a decision about medication that is best for both the woman and her baby.

The risk of relapse in pregnancy and after birth is high, particularly if there has ever been a diagnosis of bipolar disorder, schizoaffective disorder, or severe depression. Women who stop lithium treatment suddenly have a high chance of relapse.

If a woman is taking lithium during pregnancy, she should have her blood levels of lithium checked often and may need to increase her dose during pregnancy to prevent relapse.

Breastfeeding

Lithium passes easily into babies' circulation through breast milk, giving the baby a high level of lithium in their blood. The National Institute for Health and Care Excellence and the British Association of Psychopharmacology recommend not breastfeeding while taking lithium. However, there have been some cases of women successfully breastfeeding when taking lithium. If a woman does wish to breastfeed while taking lithium, she will need to monitor her baby's lithium level, thyroid, and kidney function.

Anticonvulsants during pregnancy and breastfeeding

Anticonvulsants are a class of drugs used to treat bipolar disorders. They are also known as mood stabilizers. While they are effective in managing acute episodes of mania or depression, they are also used to prevent the relapse or recurrence of symptoms.

Pregnant women with bipolar disorder are at a high risk of relapse of symptoms during pregnancy and the early postpartum period. The risk of relapse during pregnancy is estimated to be 50% or more, with a recurrence risk 2.3 times higher after discontinuing mood stabilizers.

The decision to continue or discontinue mood stabilizers during pregnancy is a complex one, as it involves weighing the risks of fetal exposure to drugs against the risks of untreated maternal illness. This decision should be made by the patient in consultation with their clinician, taking into account the patient's history of illness and response to treatment.

During pregnancy, the choice of mood stabilizer should be based on a balance between safety and efficacy. Close and intensive monitoring is recommended for patients on psychotropic medication.

Among the various mood stabilizers, the use of lithium during the second and third trimesters appears to be safe. However, the use of valproate and carbamazepine during the first trimester is associated with a higher risk of major congenital malformations and long-term developmental issues. Data for lamotrigine (LTG) appears to be more favorable than other antiepileptics, and its use during lactation is reported to be safe.

Breastfeeding is important for the development of an emotional bond and attachment between the mother and infant, and it also confers health benefits to both. When deciding whether to continue breastfeeding while taking mood stabilizers, a risk-benefit analysis should be performed, taking into account the benefits of breastfeeding, the potential adverse effects of untreated maternal mental illness, and the impact of psychotropic medication on the infant's cognitive and behavioral development.

While there is limited data on the safety of atypical antipsychotics during pregnancy and lactation, studies suggest that olanzapine, risperidone, quetiapine, and clozapine are relatively safe. However, ziprasidone has been associated with possible teratogenic effects, and aripiprazole has shown developmental toxicity in animal studies.

Recommendations from Psychiatrists vs. Neurologists

A study comparing the recommendations of neurologists and psychiatrists regarding the use of anticonvulsants during pregnancy and lactation found significant differences between the two specialties. Neurologists were more likely to encourage pregnancy and breastfeeding in women receiving anticonvulsant therapy, while psychiatrists were more cautious, citing potential long-term neurobehavioral risks and possible complications of breastfeeding. These differences may reflect the availability of alternative treatments for mood disorders that may be less risky during pregnancy and the postpartum period.

Antipsychotics during pregnancy and breastfeeding

Antipsychotics are medicines used to treat several types of mental illness, most often schizophrenia and bipolar disorder, and less often severe anxiety or depression. They can also be used to prevent and treat postpartum psychosis, a severe type of mental illness that starts soon after birth. Antipsychotics can be prescribed as tablets, injections, or long-acting injections (also called 'depots'), which can be given weekly, fortnightly, or monthly.

Deciding whether to take antipsychotics during pregnancy

Pregnant women may need to take medication for physical and mental health problems. If you want to get pregnant, you will need to decide whether to continue, stop, or change any medication you take. This includes antipsychotics. You may have to make this decision after you find out you are pregnant, as many pregnancies are unplanned.

It can be difficult to decide about taking a medication during pregnancy. We often don't have enough information to say that a medication is 100% safe. What you can do is weigh up the risks and benefits for you and your baby. You may have to think about:

• How often and how severe your episodes of illness have been.
• Medications that have helped, made no difference, or caused side effects.
• How you and your baby might be affected if you become unwell while pregnant or after birth.
• How antipsychotics and other medications might affect your baby.

If you have already had an episode of severe mental illness, it’s important to think carefully about the risks of stopping or changing medication, as it can make you unwell again. Pregnancy does not protect against mental illness, and you will have a higher risk of getting unwell during pregnancy or after you have had your baby if you have had a diagnosis of schizoaffective disorder, other psychotic illnesses, or bipolar disorder.

The National Institute for Health and Care Excellence (NICE) recommends that you should continue an antipsychotic if, without it, you are likely to become unwell again. If you do not have a psychiatrist, your GP should refer you to one, ideally a perinatal psychiatrist—an expert in caring for women who have mental health problems in pregnancy and after birth.

What to do if you want to get pregnant and are already taking an antipsychotic

Talk to your psychiatrist or GP as soon as possible. They can refer you for a pregnancy planning appointment with a perinatal psychiatrist, who can help you decide whether it is best to continue, change, or stop a medication. The benefits of continuing antipsychotic medication will often outweigh the risks, both for you and your baby. But you will need to talk over the different issues involved with your psychiatrist before making your decision.

If you do decide to stop your antipsychotic medication, make sure that:

• You don’t do it suddenly, as this may make you unwell again.
• You see someone from the psychiatric team regularly, so they can keep a close eye on your mental health.
• You and your family know how to get help if you do become unwell.

At the pregnancy planning appointment, you can also discuss other issues, including your risk of becoming unwell again during pregnancy and after birth and the care and support available for you and your family.

Valproate pregnancy warning

Valproate is a mood stabiliser used to treat bipolar disorder and epilepsy. It is also used off-label for other conditions, such as migraine prophylaxis. Valproate is associated with significant teratogenic risks, and its use is now banned in many countries for women who are pregnant or could become pregnant.

Valproate use during pregnancy has been linked to an increased risk of congenital malformations, including spina bifida, cleft palate, hypospadias, polydactyly, and craniosynostosis. The risk of congenital malformations is dose-dependent, with higher doses of valproate associated with a higher risk of abnormalities. The risk is also increased when women require polytherapy.

Valproate exposure in utero has also been associated with long-term neurodevelopmental problems, including autism spectrum disorder, and reduced IQ. The risk of autism spectrum disorder in children exposed to valproate in utero has been estimated at around 4%.

In addition to the risks to the foetus, there are also risks to the mother associated with valproate use during pregnancy. These include an increased risk of seizures and poorer developmental outcomes.

Given the risks associated with valproate use during pregnancy, it is recommended that valproate should not be used in women of childbearing age unless other treatments are ineffective or not tolerated. If valproate is used, it is recommended that the dose is kept below 1000mg/day, and that high-dose folate is taken periconceptually to reduce the risk of some malformations and cognitive impairment.

Further support during pregnancy and breastfeeding

Deciding whether to continue or discontinue mood stabilizers during pregnancy is a complex issue that requires careful consideration of the risks to the unborn child and the risks of a bipolar relapse. It is important to note that none of the mood stabilizers are completely safe or free from risk. Here are some further considerations for pregnant women taking mood stabilizers:

• Lithium: Lithium is associated with a small but relatively low teratogenic risk. It can be considered for specific indications, such as the presence of lifetime suicidality or for patients who have responded well to lithium in the past. However, it is important to monitor lithium levels frequently during pregnancy as the physical changes can cause fluctuations. Women taking lithium should also be well-hydrated, especially around delivery, to reduce the risk of lithium toxicity.
• Anticonvulsants: Certain anticonvulsants, such as valproate, carry a high risk of congenital malformations and neurodevelopmental disorders in children exposed in utero. These medications should be avoided during pregnancy. Carbamazepine and lamotrigine have lower teratogenic risks but are still associated with potential risks. It is important to consult with a healthcare professional to weigh the benefits against the risks.
• Antipsychotics: Second-generation antipsychotics, such as olanzapine, quetiapine, and aripiprazole, appear to be relatively safe during pregnancy. However, risperidone may have a slightly increased risk of congenital malformations. More research is needed for newly marketed antipsychotics such as lurasidone. It is important to monitor pregnant women taking olanzapine and quetiapine for gestational diabetes mellitus.
• Benzodiazepines: While most benzodiazepines were not associated with a congenital anomaly risk, they should still be used with caution during pregnancy due to potential adverse neonatal outcomes. They may increase the risk of spontaneous abortion, preterm birth, and other adverse outcomes.
• Antidepressants: Selective serotonin reuptake inhibitors (SSRIs) have been associated with a small but significant increase in the risk of fetal cardiac malformations, particularly with paroxetine. Other antidepressants, such as mirtazapine and venlafaxine, have limited safety data, but the reported risks of congenital malformations appear similar to SSRIs.
• General Considerations: Pregnancy involves physiological changes that can affect drug levels. It is important to monitor drug levels frequently and consider dose adjustments. Collaborative care involving multiple healthcare professionals is recommended for pregnant women with bipolar disorder.

Frequently asked questions