What are the guidelines for using tricyclic antidepressants (TCAs) in pregnancy?

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Last updated: July 3, 2025View editorial policy

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From the Research

Tricyclic antidepressants (TCAs) should be used cautiously during pregnancy, with the decision to initiate or continue treatment based on a careful risk-benefit assessment. For pregnant women requiring TCA therapy, nortriptyline seems to be the safest medication, especially during breastfeeding, as suggested by the most recent and highest quality study 1. Dosing should start low and increase gradually, with therapeutic drug monitoring recommended to maintain effective levels while minimizing side effects. TCAs are considered second-line treatments after selective serotonin reuptake inhibitors (SSRIs) like sertraline and citalopram. The risks of untreated depression during pregnancy, such as poor prenatal care, inadequate nutrition, increased substance use, and potential self-harm, often outweigh the modest risks associated with TCAs, which include possible mild, transient neonatal adaptation symptoms.

Some key points to consider when using TCAs in pregnancy include:

  • No consistent pattern of major congenital malformations has been established with TCA use 1, 2.
  • Treatment should be coordinated between obstetric and psychiatric providers, with consideration of dose reduction 2-4 weeks before delivery to minimize neonatal adaptation issues, though this must be balanced against the risk of maternal relapse.
  • Nortriptyline, amitriptyline, and desipramine are generally preferred options due to their better-established safety profiles, although nortriptyline is highlighted as the safest in more recent studies 1.
  • The use of TCAs, especially clomipramine, may be associated with a higher risk of prenatal antidepressant exposure syndrome and neonatal symptoms, but the evidence is not conclusive 1.

Given the potential risks and benefits, the use of TCAs in pregnancy should be carefully considered, with nortriptyline being a preferred option due to its safety profile, especially when breastfeeding is a consideration 1.

References

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This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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