What are the risks and recommendations for using Nortriptyline (nortriptyline) and Pristiq (desvenlafaxine) during pregnancy?

Nortriptyline and Desvenlafaxine (Pristiq) Use During Pregnancy: Risks and Recommendations

Both nortriptyline and desvenlafaxine should be used during pregnancy only when the potential benefits to the mother outweigh the possible risks to the fetus, as neither medication has established safety during pregnancy. 1, 2

Nortriptyline in Pregnancy

Safety Profile

• Safe use of nortriptyline during pregnancy has not been established, and animal reproduction studies have yielded inconclusive results 1
• Nortriptyline is a tricyclic antidepressant (TCA) that primarily increases norepinephrine levels in the brain, with less effect on serotonin compared to SSRIs 3

Risks

• Limited data on specific risks of nortriptyline during pregnancy compared to other antidepressants 3
• As with other antidepressants, potential risks include:
  • Possible increased risk of spontaneous abortion, though confounding by indication cannot be ruled out 3
  • Potential for poor neonatal adaptation syndrome when used late in pregnancy 3

Desvenlafaxine (Pristiq) in Pregnancy

Safety Profile

• There are no published studies specifically on desvenlafaxine in pregnant women 2
• Desvenlafaxine is an SNRI (serotonin-norepinephrine reuptake inhibitor) and is the active metabolite of venlafaxine 2

Risks

• Studies on venlafaxine (parent compound) have not reported a clear association with major birth defects or miscarriage, though methodological limitations exist in these studies 2
• Potential risks associated with SNRIs in pregnancy include:
  • Increased risk for preeclampsia when used in mid to late pregnancy 2
  • Increased risk for postpartum hemorrhage when used near delivery 2
  • Neonatal complications requiring prolonged hospitalization, respiratory support, and tube feeding when exposed in late pregnancy 2
  • Risk of neonatal drug discontinuation syndrome with third-trimester exposure 2

General Considerations for Antidepressant Use in Pregnancy

Risk-Benefit Assessment

• Untreated depression during pregnancy is associated with adverse outcomes including:
  • Premature birth 3
  • Decreased initiation of breastfeeding 3
• Discontinuing antidepressants during pregnancy significantly increases the risk of relapse of major depression 2

Monitoring Recommendations

• For women taking desvenlafaxine during pregnancy:
  • Register with the National Pregnancy Registry for Antidepressants (1-844-405-6185) 2
  • Monitor for signs of preeclampsia, especially in mid to late pregnancy 2
  • Be prepared for potential postpartum hemorrhage if used near delivery 2
• For neonates exposed to either medication in the third trimester:
  • Monitor for drug discontinuation syndrome 2
  • Watch for poor neonatal adaptation, which may include respiratory issues, feeding difficulties, and neurological symptoms 3

Timing Considerations

• First trimester: Concerns primarily focus on potential teratogenic effects, though neither drug has strong evidence of causing major malformations 1, 2
• Second and third trimesters: Concerns shift to pharmacological effects on the developing fetus and preparation for potential neonatal adaptation issues 4

Clinical Decision-Making Algorithm

1. Assess severity of maternal depression

   • If depression is severe with significant functional impairment or suicidality, benefits of treatment likely outweigh risks 2
   • If depression is mild to moderate, consider non-pharmacological approaches first 4

2. Consider pregnancy stage

   • If planning pregnancy: Discuss risks/benefits before conception
   • If already pregnant: Evaluate current trimester and adjust approach accordingly 4

3. Medication selection if treatment is necessary

   • For women already stable on nortriptyline or desvenlafaxine, continuing may be preferable to switching medications or discontinuing 2
   • For women starting new treatment, medications with more pregnancy safety data might be preferable 3

4. Dosing considerations

   • Physiological changes in pregnancy may alter drug metabolism, potentially requiring dose adjustments, particularly in the third trimester 5
   • Close monitoring of therapeutic response and side effects is recommended 5

Important Caveats

• The background risk of major birth defects in the general population is 2-4%, and miscarriage is 15-20% 2
• Most studies on medication safety in pregnancy have methodological limitations including potential confounding by indication 2
• Avoid abrupt discontinuation of either medication during pregnancy due to risk of withdrawal symptoms and depression relapse 2
• Decision-making should weigh the risks of untreated depression against potential medication risks 1, 2