Which antidepressant is safer for a breastfeeding woman, nortriptyline (tricyclic antidepressant) or fluoxetine (SSRI)?

Antidepressant Choice for Breastfeeding Women: Nortriptyline vs Fluoxetine

Choose nortriptyline over fluoxetine for a breastfeeding woman, as nortriptyline is undetectable in infant serum and has no reported adverse effects, while fluoxetine produces the highest infant plasma concentrations among SSRIs and has been associated with adverse effects in nursing infants. 1, 2

Evidence-Based Rationale

Nortriptyline Safety Profile

• Nortriptyline is not found in quantifiable amounts in nursing infants' serum, making it one of the safest antidepressants during breastfeeding 2, 3
• No adverse effects have been reported in infants exposed to nortriptyline through breast milk 2
• Nortriptyline is specifically identified as one of the most evidence-based medications for use during breastfeeding 3
• The drug has a well-established safety profile with extensive clinical experience in lactating women 4

Fluoxetine Concerns

• Fluoxetine produces the highest infant plasma concentrations among all SSRIs and has been associated with more frequent reports of suspected adverse effects in infants 1
• The FDA label documents a case where an infant nursed by a mother on fluoxetine developed crying, sleep disturbance, vomiting, and watery stools, with infant plasma drug levels of 340 ng/mL fluoxetine and 208 ng/mL norfluoxetine 5
• Approximately 10.8% of the maternal dose (adjusted for infant weight) is transferred to the infant through breast milk 6
• Fluoxetine must be used carefully during lactation and is not a first-line choice 4
• The FDA explicitly states that "nursing while on Prozac is not recommended" 5

Clinical Algorithm for Decision-Making

When Nortriptyline is Preferred:

• Any breastfeeding woman requiring antidepressant therapy where both medications are clinically appropriate 2, 3
• Women concerned about infant drug exposure 1
• Infants under 10 weeks of age (though nortriptyline is safe at all ages) 2

Monitoring Requirements for Nortriptyline:

• Monitor infant for irritability, excessive crying, poor feeding, unusual drowsiness, and adequate weight gain 1
• Arrange early follow-up after initiating treatment 1
• Infants older than 10 weeks are at particularly low risk, with no evidence of drug accumulation 2

If Fluoxetine Must Be Used:

• Only consider if the mother is already stabilized on fluoxetine and switching medications poses greater risk 7
• Use the lowest effective dose 8
• Monitor infant closely for irritability, sleep disturbance, feeding difficulties, vomiting, and gastrointestinal symptoms 5
• Obtain early pediatric follow-up 1

Important Clinical Caveats

The collective evidence strongly favors nortriptyline over fluoxetine for breastfeeding women. While fluoxetine may be continued in women already taking it who wish to breastfeed, it should not be initiated as first-line therapy when safer alternatives like nortriptyline exist 1, 2, 3. The undetectable infant serum levels with nortriptyline versus measurable and sometimes clinically significant levels with fluoxetine make this choice clear from a risk-benefit perspective 2, 6.

If an SSRI is specifically required for clinical reasons, sertraline or paroxetine would be preferred over fluoxetine, as they transfer into breast milk in the lowest concentrations 1, 9. However, between the two medications in your question, nortriptyline is definitively the safer choice 2, 3, 4.