How should lithium dosage be adjusted during pregnancy to minimize risks?

Lithium Dosage Adjustment During Pregnancy

Lithium dosage should be increased by approximately 50% during the third trimester of pregnancy to maintain therapeutic levels, with weekly serum monitoring required throughout pregnancy and immediate dose reduction during labor and delivery to prevent toxicity.

Physiological Changes Affecting Lithium Levels During Pregnancy

Pregnancy significantly alters lithium pharmacokinetics due to several physiological changes:

• Increased glomerular filtration rate (GFR) leads to enhanced renal clearance
• Expanded blood volume causes dilution of serum concentrations
• Changes in total body water affect distribution
• Altered renal tubular reabsorption impacts excretion

Research shows that dose-adjusted serum lithium concentrations decrease by approximately 34% in the third trimester compared to non-pregnant baseline values 1. This necessitates dosage adjustments to maintain therapeutic levels.

Recommended Monitoring Protocol

1. Preconception planning:

   • Establish stable baseline lithium levels before pregnancy if possible
   • Discuss risks and benefits of continuing lithium during pregnancy

2. First trimester:

   • Monitor lithium levels every 2 weeks
   • Consider risk of teratogenicity (especially cardiac anomalies like Ebstein's anomaly) 2
   • Schedule high-resolution ultrasound with fetal anomaly scanning at 20 weeks 3

3. Second trimester:

   • Monitor lithium levels every 2 weeks
   • Begin gradual dose increases as clearance increases

4. Third trimester:

   • Increase monitoring to weekly serum lithium levels 4
   • Increase lithium dose by approximately 50% to maintain therapeutic levels 1
   • Target the lower end of the therapeutic range to minimize fetal exposure

5. Labor and delivery:

   • Reduce lithium dose at onset of labor 5
   • Monitor for signs of lithium toxicity in both mother and neonate
   • Resume pre-pregnancy dosing immediately postpartum to prevent relapse 4

Specific Dosing Recommendations

• Maximum recommended dosage: 400 mg three times daily during pregnancy 6
• Avoid sodium-restricted diets and diuretics which can increase lithium levels 5
• Target serum levels: Aim for the lower end of the therapeutic range during pregnancy

Warning Signs of Lithium Toxicity

Monitor closely for:

• Maternal symptoms: tremor, confusion, ataxia, drowsiness
• Neonatal symptoms: hypotonia, lethargy, feeding difficulties, respiratory distress
• Renal function changes: polyuria, polydipsia (may indicate nephrogenic diabetes insipidus) 2

Special Considerations

• Renal function: Acute deterioration in renal function can rapidly lead to lithium toxicity 7
• Delivery planning: Ideally, delivery should take place in a specialized hospital where psychiatric and obstetric care for the mother and neonatal evaluation can occur immediately 4
• Postpartum period: Due to high risk of relapse postpartum, higher therapeutic lithium levels may be recommended after delivery 4
• Breastfeeding: Most clinical guidelines discourage breastfeeding for women on lithium 4

Common Pitfalls to Avoid

1. Failure to increase monitoring frequency during pregnancy, especially in the third trimester
2. Not adjusting dosage despite changing serum levels
3. Maintaining pre-pregnancy dosing during the third trimester (likely to result in subtherapeutic levels)
4. Not reducing dose during labor which can lead to toxicity
5. Delaying postpartum dose adjustment which increases relapse risk

Careful monitoring and appropriate dosage adjustments are essential to balance the need for maternal psychiatric stability with minimizing fetal exposure to lithium during pregnancy.