Perinatal Bipolar

• Risks
  • Those who discontinue mood stabilizers during pregnancy, 66% relapse postpartum
  • Those who continue mood stabilizers during pregnancy, 23% relapse postpartum
  • Abrupt interruption of mood stabilizer may precipitate decompensation
  • Recurrence during pregnancy
    • Typically depressive or mixed
    • Most occur early
    • Earlier with rapid discontinuation (<14 days taper)
  • High risk of postpartum mood disorder or psychosis
  • pregnant women with psychiatric illness have higher rate of adverse outcomes including pre-eclampsia, C-section, gestational diabetes
  • Children exposed to peripartum depression have higher cortisol levels that mothers not depressed, continues through adolescence
  • Untreated antepartum depression is one of the strongest risk factors for postpartum depression
    • Suicide accounts for up to 20% of all postpartum deaths
• Guiding principles
  • mild illness that has been stable without medication for years
    • attempt to withhold mood stabilizers during first trimester
    • low dose lithium or other low dose medication (e.g., atypical)
  • moderate to severe illness
    • continue mood stabilizers and other psychiatric medications to maintain stability
• Reasonable Treatment Choices
  • Lithium, lamotrigine
    • well-characterized reproductive safety profiles
    • low absolute risks
  • Lithium is a good choice for women at risk for mania
  • Lamotrigine a good choice to prevent bipolar depression (but not mania)
  • Atypical antipsychotics - data growing, do not appear to be teratogenic

Lamotrigine

• Risk: no significant risks, but could be always be possible with higher doses
• use lowest effective dose
• Earlier concern for oral clefts
  • numerous studies and large meta-analysis have found no evidence for significant increased risk of oral clefts relative to other non-chromosomal malformations
  • absolute risk of oral cleft is 0.7%
• No increased risk of adverse pregnancy outcome (SGA, SAB, fetal demise, preterm delivery)
• Check levels
  • higher level of estrogen during pregnancy enhances lamotrigine clearance (P450) may result in sub-therapeutic concentrations
    • notable by week 10
    • If possible, get trough level before pregnancy or soon after conception when pt is on therapeutic dose
    • check levels and symptoms
  • Levels of lamotrigine return to pre-pregnancy values within 4 weeks postpartum
    • taper dose postpartum day 5 through day 14 to pre-pregnancy dose
    • postpartum toxicity if dose not adjusted
      • diplopia, ataxia, nausea, dizzy

Lithium

• Cardiac malformation with first trimester exposure: about 1 additional per 100
  • Risk increased 3-fold in doses above 900 mg daily
    • consider lowering dose in first trimester
    • consider lamotrigine - but often not as effective as lithium (especially mania); or consider atypical antipsychotic
  • Difficult to adjust Li dose after positive pregnancy test before critical window of heart development (4-8 w)
• No association with spontaneous abortion, low birth weight or preterm labor
• Management
  • If possible avoid situations that tend to increase lithium levels
    • NSAIDs, diuretics, ACEI, Ca channel blockers
    • sodium-restricted diets
  • Monitor for maternal lithium toxicity
    • acute fluid loss
    • hyperemesis gravidarum
    • preeclampsia
  • Monitor fetal development
    • Nuchal translucency (12 w)
    • Level 2 structural ultrasound (18-20 w)
    • Fetal echocardiogram
• Dosing
  • twice daily dosing recommended
  • levels decrease throughout pregnancy
    • maintain lithium concentration and minimum clinically effective levels, otherwise why even bother given risk
    • monitor levels every 3 weeks until 34 weeks, weekly thereafter
• Labor and Delivery
  • Maintain fluids throughout
  • Do not discontinue
  • Monitor twice weekly during first two weeks after delivery with goal being preconception lithium level and clinical stability

Atypical Antipsychotic

• Currently available data does not suggest signal of teratogenicity
  • per National Pregnancy Registry for Atypical Antipsychotics
• Pregnant women with serious psychiatric illness, use of atypical antipsychotics may be the prudent choice
• Neonatal EPS symptoms
  • FDA labeling change includes typical and atypical antipsychotics
  • Typically not with monotherapy
  • Suggest observe in special care nursery 48 hours postpartum
  • Symptoms
    • agitation
    • increased or decreased muscle tone, tremors
    • sleepiness
    • breathing and feeding difficulties