What should a provider do for a patient on Lithium (lithium carbonate) and Cymbalta (duloxetine) who is planning to get pregnant?

Management of Lithium and Duloxetine in Pregnancy Planning

Discontinue lithium immediately when pregnancy is confirmed or ideally before conception, and taper duloxetine gradually rather than stopping abruptly, while ensuring close psychiatric monitoring throughout the transition.

Lithium Management

Preconception Planning

• Lithium is contraindicated in pregnancy due to well-established teratogenic effects, particularly cardiac malformations (Ebstein's anomaly) 1, 2, 3
• Discontinue lithium at least 2-3 months before attempting conception to allow complete washout and stabilization on alternative mood stabilizers 4
• The decision to stop lithium must be weighed against the risk of bipolar relapse, which itself poses significant risks to both mother and fetus 5, 6

Alternative Mood Stabilizers

• Consider switching to pregnancy-compatible options before conception 4:
  • Lamotrigine (preferred for bipolar maintenance in pregnancy planning)
  • Atypical antipsychotics such as aripiprazole (though minimize polypharmacy if possible) 5
• If mood destabilization occurs during lithium taper, reintroduce the safest effective alternative rather than resuming lithium 5

Critical Timing Considerations

• Do not wait until pregnancy is confirmed to discontinue lithium—the critical period for cardiac teratogenesis is weeks 2-8 of gestation, often before pregnancy recognition 2, 3
• Ensure reliable contraception is in place during the medication transition period 4

Duloxetine (Cymbalta) Management

Pregnancy Safety Profile

• Duloxetine may be continued during pregnancy as the FDA label states it "may harm your unborn baby" but does not establish definitive teratogenicity 1
• The American College of Obstetricians and Gynecologists notes that abrupt discontinuation of psychiatric medications poses greater risk to mother and fetus than continued treatment 5
• SSRIs and SNRIs should be continued at the lowest effective dose during pregnancy according to the American Academy of Pediatrics 7

Discontinuation vs. Continuation Decision

• If duloxetine is treating major depression or generalized anxiety disorder that is well-controlled, continuation is generally preferred over discontinuation 7, 5, 6
• If discontinuation is chosen, taper gradually over several weeks to avoid discontinuation syndrome—never stop abruptly 1, 6
• Duloxetine discontinuation syndrome includes dizziness, nausea, headache, irritability, and sensory disturbances 1

Neonatal Considerations

• Neonates exposed to duloxetine in late third trimester may develop transient neonatal adaptation syndrome (irritability, tremors, poor feeding, respiratory symptoms) that typically resolves within 1-4 weeks 7
• Multiple reviews show no adverse neurodevelopmental outcomes from SSRI/SNRI exposure during pregnancy 7
• Inform the pediatric team about maternal duloxetine use for appropriate neonatal monitoring 7

Essential Preconception Interventions

Folic Acid Supplementation

• Initiate 400 mcg daily folic acid immediately if not already taking, continuing through first trimester to reduce neural tube defect risk by 75% 5
• Higher doses (4-5 mg daily) are reserved for women with specific risk factors such as prior neural tube defect or certain antiepileptic drug use 5

Psychiatric Stability Assessment

• Achieve optimal disease control before conception with pregnancy-compatible medications 4
• Postpone conception if active psychiatric illness is present until remission or low disease activity is achieved 4
• Establish close psychiatric follow-up throughout pregnancy planning and pregnancy 7, 6

Contraception During Transition

• Use reliable contraception during the medication transition period to avoid unplanned pregnancy exposure to lithium 4
• Perform frequent pregnancy tests once attempting conception to enable early medication adjustments 4

Shared Decision-Making Framework

Risk Communication

• Untreated maternal psychiatric illness carries significant risks: increased risk of adverse pregnancy outcomes, poor prenatal care adherence, substance use, and postpartum complications 4, 5
• The risk-benefit analysis must weigh medication risks against the substantial risks of untreated illness 4, 1
• Most medications have risks that are lower than commonly perceived by both patients and providers 2, 8, 3

Patient Counseling Points

• Discuss that only approximately 20 drugs are definitively known to cause birth defects in humans, and lithium is one of them 3
• Explain that for duloxetine, the evidence does not establish definitive teratogenicity, though data are limited 1, 2
• Emphasize the importance of planned pregnancy to optimize medication regimen before conception 4

Common Pitfalls to Avoid

• Do not abruptly discontinue duloxetine when pregnancy is discovered—this precipitates withdrawal syndrome and psychiatric relapse 1, 6
• Do not continue lithium during pregnancy based on patient reluctance to change medications—the teratogenic risk is well-established 2, 3
• Do not delay preconception counseling until the patient is actively trying to conceive—early planning allows adequate time for medication transitions 4
• Do not underestimate the risk of psychiatric relapse during medication changes—close monitoring is essential 5, 6

Breastfeeding Considerations

• Duloxetine passes into breast milk but is generally compatible with breastfeeding, though infant monitoring for irritability and feeding difficulties is recommended 5, 1
• Lithium is excreted in breast milk at significant concentrations and is generally not recommended during lactation 4
• The benefits of breastfeeding should be weighed against medication exposure risks using shared decision-making 4