Which Bipolar Medications Are Safest During Pregnancy?

The short answer: No bipolar medication is risk-free in pregnancy, and no source names one safest drug for everyone. The 2023 ACOG guideline advises against valproate in pregnancy and advises against stopping other mood stabilizers. FDA labels and large studies report lower birth defect risks for lamotrigine and quetiapine than for valproate, and a small heart defect risk for lithium. Do not stop or change a medicine without your prescriber.

Why is there no single safest drug?

Each option has a different risk, and the illness has a risk too. A drug that keeps one person well may not work for another. So the question is which plan carries the lowest total risk for you and your baby.

It helps to know the starting point. FDA labels state that the background risk of major birth defects in the U.S. general population is 2 to 4% of pregnancies. Every number below sits on top of that baseline.

ACOG's Clinical Practice Guideline No. 5 says that for most people and most medications, the risk of the exposure is lower than the risk of relapse. It also says a clinically stable person should generally continue the same regimen. A switch exposes the fetus to more than one drug and may raise the risk of a new mood episode. Valproate is the stated exception. For a wider view of these drugs, see our guide to mood stabilizers.

What is the risk of stopping medication during pregnancy?

The risk is high, and it is the reason this choice is hard. A prospective study in the American Journal of Psychiatry followed 89 pregnant women with bipolar disorder. The overall risk of at least one recurrence in pregnancy was 71%. Women who stopped their mood stabilizer had twice the recurrence risk of women who continued.

• 47% of recurrences happened in the first trimester.
• Most recurrences (74%) were depressive or mixed episodes.
• Recurrence came much sooner after an abrupt stop than after a gradual one.

The weeks after birth are also a high-risk time. A meta-analysis of 4,023 patients found a postpartum relapse rate of 66% in women with bipolar disorder who took no medication in pregnancy. The rate was 23% in women who took preventive medication.

ACOG adds that untreated bipolar disorder is linked to postpartum psychosis, hospitalization, preterm birth, and poor fetal growth. Because most relapses in pregnancy are depressive, the symptoms can look like ordinary low mood. Our sister site depression.md covers those symptoms. We also explain what happens when lithium is stopped.

What do the labels say about valproate and carbamazepine?

Valproate has the strongest warning of any bipolar drug. The Depakote label carries a boxed warning for fetal risk. It states that valproate can cause major birth defects, particularly neural tube defects such as spina bifida. It also states that valproate can cause lower IQ scores and neurodevelopmental disorders after exposure in the womb.

The label gives these figures:

• Spina bifida occurs in about 0.06 to 0.07% of births in the general population. The estimate after valproate exposure is about 1 to 2%.
• A North American registry reported major malformations in 9 to 11% of babies exposed to valproate alone, at an average of 1,000 mg per day.
• The risk is dose-dependent, but no dose is known to be free of risk.

For bipolar disorder, the label says valproate should not be used in women who are pregnant or plan a pregnancy unless other medications have failed or are otherwise unacceptable. ACOG recommends against valproate as a first-line treatment and says it should be avoided in pregnancy, in any trimester.

The carbamazepine (Tegretol) label states that the drug can cause fetal harm. It reports a possible association with birth defects, including spina bifida, and reports of developmental delays. ACOG notes that most experts recommend a move away from carbamazepine before pregnancy. That is a conversation to have before conception, not a change to make alone.

How large is the heart defect risk with lithium?

It is real, but smaller than doctors once thought. Early reports linked first-trimester lithium to a rare heart defect called Ebstein's anomaly. The current lithium label says later studies indicate the increased risk of heart defects is likely to be small.

The largest study is a 2017 cohort in the New England Journal of Medicine of 1,325,563 pregnancies. Heart defects occurred in 2.41% of 663 infants exposed to lithium and in 1.15% of unexposed infants. The adjusted risk ratio was 1.65. The risk rose with the dose.

ACOG says these newer data make lithium a reasonable option, particularly for people with a history of mania. It recommends a detailed ultrasound in the second trimester after first-trimester exposure. The label adds two cautions. Lithium blood levels need monitoring and dose adjustment in pregnancy, and newborns exposed late in pregnancy can show signs of lithium toxicity. MotherToBaby notes that a quick stop of lithium may cause a relapse.

What do the registries show for lamotrigine?

The registry data are reassuring so far. The Lamictal label says several pregnancy registries have not found more major birth defects than in the general population. It cites three registries:

• International Lamotrigine Pregnancy Registry: 2.2% of 1,558 exposed infants.
• North American Antiepileptic Drug (NAAED) Pregnancy Registry: 2.0% of 1,562 infants.
• EURAP: 2.9% of 2,514 exposures.

There is one caveat. The NAAED registry saw oral clefts in 3.2 per 1,000 exposed infants. The label says other large registries have not seen this, and MotherToBaby reports the same. Most of the data also come from women with epilepsy, not bipolar disorder.

Blood levels are the practical problem. The label reports lower lamotrigine concentrations during pregnancy, with a return to earlier levels after delivery. ACOG explains that pregnancy speeds up the clearance of the drug, so prescribers may check levels and adjust the dose. Lamotrigine must also be started slowly, as our article on the Lamictal rash warning explains. ACOG notes that this makes it hard to start during pregnancy.

What is known about quetiapine and other antipsychotics?

The Seroquel label says published studies have not established a drug-associated risk of major birth defects or miscarriage with quetiapine. A JAMA Psychiatry study of 1,341,715 pregnancies included 9,258 women who filled a prescription for a second-generation antipsychotic in the first trimester. After adjustment, the relative risk of birth defects was 1.05, which was not a significant increase. Risperidone showed a small increase (relative risk 1.26) that the authors said needs more study.

Two cautions remain. The label warns that babies exposed in the third trimester can have movement or withdrawal symptoms after birth. ACOG notes that quetiapine has metabolic risks, including weight gain and gestational diabetes. ACOG also says there are fewer published pregnancy data for the newer antipsychotics than for older ones. It describes quetiapine as often preferred among antipsychotics because of its low passage across the placenta.

How do you and your doctors make the choice?

ACOG says a visit before pregnancy is the ideal time for this decision. It recommends that a psychiatrist or other mental health specialist work with the obstetric team. Useful points to raise:

• Which medicines have kept you well, and what happened when you stopped them.
• Whether your history includes mania, psychosis, or a past postpartum episode.
• What monitoring the plan needs, such as blood levels or a detailed ultrasound.
• The plan for delivery and the first weeks after birth.

Pregnancy registries collect outcome data to help future patients. The National Pregnancy Registry for Psychiatric Medications at Massachusetts General Hospital tracks antipsychotics and other psychiatric drugs. The Seroquel label lists its number as 1-866-961-2388. The NAAED registry tracks lamotrigine, valproate, and carbamazepine at 1-888-233-2334. If you are already pregnant, call your prescriber before you change anything.

The bottom line

No bipolar medication is proven safe in pregnancy, and untreated bipolar disorder is not safe either. Valproate carries the strongest FDA warning, and ACOG says to avoid it in pregnancy. Lamotrigine, lithium, and quetiapine each have lower reported risks, with different cautions for each. The right plan depends on your history. Make it with your psychiatrist and obstetrician, before conception if you can.

Last updated: October 2026. This article is for informational purposes only and does not constitute medical advice. Do not start, stop, or change any medication in pregnancy without your prescriber.