antidepressant treatment and breast feeding

Last edited 02/2023

Post-natal depression has the dilemma of frequent improvement with anti-depressant drugs, so improving maternal-infant bonding, but passage of the same drugs to infant in breast milk.

  • antidepressant therapy is indicated for women who have severe depression or who fail to respond to appropriate counselling

  • tricyclic antidepressants (TCA) are relatively safe but most manufacturers advise avoid. The accumulation of doxepin metabolite may cause respiratory depression and sedation (1)

SSRIs and breastfeeding

  • the majority of SSRIs are not licensed for use in breast feeding and manufacturers recommend that they are not used during lactation. Summary points re: SSRIs (2)

    • paroxetine and sertraline are the SSRIs of choice during breastfeeding
      • paroxetine and sertraline have shorter half-lives and pass into milk in smaller amounts compared to others, and are therefore preferred
      • paroxetine:
        • published evidence shows that paroxetine passes into breast milk in very small amounts (ranging from 0.1%-4.3% of the weight-adjusted maternal dose) with maternal doses up to 60mg daily
        • in one study, paroxetine was detected in infant serum as 5% of the maternal serum level. In other studies paroxetine has not been detectable in infant serum
        • in most cases short or longer-term infant side-effects have not been reported
          • note that there have been occasional reports of irritability, insomnia, restlessness, poor feeding, sedation and constipation. A single case of severe hyponatraemia has been described, although causality was not proven
          • side-effects are reported more often when paroxetine is also taken during pregnancy
        • suggested infant monitoring
          • as a precaution, monitor for irritability, restlessness, drowsiness, constipation, poor feeding and adequate weight-gain

      • sertraline:
        • evidence shows sertraline passes into breast milk in very small amounts (0.2-2.4% of the weight-adjusted maternal dose) with maternal doses up to 200mg daily. In many cases, the amount in breast milk was negligible
          • one study found no correlation between dose and milk levels
        • levels of sertraline (or the active metabolite norsertraline) in infant serum are very small (on average 2% of maternal serum levels for sertraline) or undetectable with maternal doses up to 200mg. In a few cases, the infant serum level was reported as greater than 10%
        • generally, infant side-effects have not been reported. Six-month follow-up studies show normal weight gain and neurological development
        • have been occasional reports of jitteriness, restlessness, agitation, poor feeding, diarrhoea, sleep disturbances, insomnia, and sedation
          • one case reported toxicity in a preterm infant (hyperthermia, effects on muscle tone, tremor, shivering and irritability); the mother had been taking 150mg sertraline during pregnancy and the infant was found to have genetically reduced sertraline metabolism
        • despite sertraline being a known inhibitor of platelet function, no such effects have been detected in infants exposed via breast milk
        • suggested infant monitoring
          • as a precaution, monitor for agitation, restlessness, insomnia, drowsiness or other sleep disturbances, diarrhoea, poor feeding and adequate weight-gain

      • citalopram:
        • can be used with caution during breastfeeding, but sertraline or paroxetine are preferred
        • evidence shows that citalopram passes into breast milk in negligible or small amounts (0.7-7.9% of the weight-adjusted maternal dose) with maternal doses up to 80mg daily
          • note that there have been 2 isolated cases reporting much higher levels (13.2% and 18.4% of the weight-adjust maternal dose)
        • infant serum levels of citalopram are low (0.9-7% of the maternal serum level). In one isolated report the infant serum level was over 10% of the maternal serum level
        • citalopram has often been used during breastfeeding without any short or longer-term infant side- effects. There have been some case reports of colic, decreased feeding, irritability, restlessness and drowsiness.
        • suggested infant monitoring
          • as a precaution, monitor for irritability, restlessness, drowsiness, colic, poor feeding and adequate weight-gain

      • escitalopram:
        • can be used with caution during breastfeeding, but sertraline or paroxetine are preferred
        • evidence shows that escitalopram passes into breast milk in small amounts (2.6%-7.7% of the weight-adjusted maternal dose) with maternal doses up to 20mg daily
        • infant serum levels have been reported as very low, and in some cases undetectable. A pharmacokinetic modelling study predicts infant serum levels to be around 1.7% of maternal serum levels
        • use of escitalopram is not usually associated with any side-effects
          • note that there have been some reports of irritability, restlessness, drowsiness, and vomiting
          • one case of necrotising enterocolitis, and one of convulsions have also been reported, although the association with breastfeeding was uncertain
        • suggested infant monitoring
          • as a precaution, monitor for irritability, restlessness, drowsiness, vomiting, poor feeding and adequate weight-gain

      • fluoxetine
        • can be used with caution
          • has been used during breastfeeding for many years, but sertraline or paroxetine are preferred
        • evidence shows that fluoxetine passes into breast milk in variable amounts (ranging from 0.54%-10.8% of the weight-adjusted maternal dose) with maternal doses of up to 80mg daily
          • some single case reports describe much higher levels; up to 20% of the weight-adjusted maternal dose
        • both fluoxetine and its active metabolite norfluoxetine have been detected in infant serum in low or undetectable levels. In one study, some infants had elevated serum levels greater than 10% of the maternal leve
          • exposure during pregnancy was thought to influence these higher levels
        • most published reports have not identified any side-effects, including longer-term neurodevelopment. However, infant side-effects are reported more often with fluoxetine compared to other SSRIs, which may reflect wider use
          • the very long half-life of fluoxetine (4-6 days), and norfluoxetine (4-16 days), greatly increases the risk of accumulation in breastfed infants
        • reported side-effects include colic, decreased sleep, vomiting, watery stools, hyperactivity, and decreased weight gain. Seizure-like activity, cyanosis, hyperglycaemia and glycosuria have also been reported, although causality has not been proven
        • two case reports of fluoxetine toxicity (tachypnoea, hypotonia, difficulty in arousing, jitteriness, and low- grade fever) have been described during breastfeeding
          • exposure during pregnancy was thought to contribute and all symptoms resolved when breastfeeding was discontinued
        • suggested infant monitoring
          • as a precaution, monitor for irritability, restlessness, drowsiness, colic, gastro-intestinal disturbances, poor feeding, and adequate weight-gain

    • SSRIs can cause discontinuation symptoms if stopped abruptly, and occurs most commonly with paroxetine
      • may make it more difficult for a breastfeeding mother to stop treatment and should be considered when making medicine choices

    • neonatal withdrawal syndrome
      • a specific withdrawal syndrome has been reported in infants exposed to SSRIs later in pregnancy, most commonly with paroxetine
      • symptoms include poor adaptation, jitteriness, irritability, poor gaze, agitation, hypotonia, and gastro- intestinal disturbances. Symptoms typically last 1 to 2 days (potentially longer with fluoxetine), but should resolve without intervention. Continuing breastfeeding may relieve withdrawal effects
      • may be difficult to distinguish between neonatal withdrawal symptoms and potential side-effects from SSRI exposure through breast milk. Symptoms common to both include agitation, jitteriness, hypotonia, and gastro-intestinal disturbances. Sedation has only been reported after exposure through breast milk. If symptoms do not resolve a few days after birth, consider that side-effects may be the potential cause

    • effect on breastfeeding
      • those taking an SSRI may have more difficulty breastfeeding, particularly with establishing breastfeeding
      • underlying disease state may contribute to this and additional breastfeeding support may be required

TCAs and breastfeeding:

  • imipramine and nortriptyline are the tricyclic antidepressants (TCAs) of choice during breastfeeding (3)
    • is because they are less sedating, therefore reducing the risk of infant sedation
    • most TCAs can be used during breastfeeding if clinically appropriate
    • limited evidence shows milk levels are very low
      • note that TCAs undergo substantial first-pass metabolism so the actual amount absorbed by the infant will be substantially less than the level reported in breast milk
    • most TCAs have relatively long half-lives
      • could result in accumulation and increased risk of side-effects due to an infant's underdeveloped clearance capacity, particularly in the neonatal period
      • note that in the majority of infants exposed in published studies, no side-effects were reported
    • TCAs can cause discontinuation symptoms if stopped abruptly
      • may make it more difficult for a breastfeeding mother to stop treatment, and should be considered when making medicine choices

  • neonatal withdrawal syndrome (3)
    • withdrawal symptoms have been reported in infants exposed to TCAs throughout pregnancy or near delivery
    • symptoms may be more severe when exposed to more than one centrally acting medicine
    • reported symptoms vary, but include
        • poor adaptation,
        • irritability,
        • jitteriness,
        • urinary retention,
        • dyspnoea,
        • lethargy,
        • colic,
        • hypotension or hypertension,
        • tachycardia, poor feeding, tremor or spasms, and seizures
      • symptoms usually resolve within two to six days
      • continuing breastfeeding may help relieve withdrawal effects
      • may be difficult to distinguish between neonatal withdrawal symptoms and potential side-effects from TCA exposure through breast milk
        • poor feeding, irritability and urinary retention could occur with both
        • sedation has only been reported after exposure through breast milk
        • if symptoms do not resolve a few days after birth, consider that side-effects may be the potential cause

  • effect on breastfeeding (3)
    • those taking TCAs may have more difficulty breastfeeding, particularly when establishing breastfeeding
    • the underlying disease state may contribute to this and additional breastfeeding support may be required

SIGN (4) state with respect to breast feeding and antidepressants:

  • avoid doxepin for treatment of depression in women who are breast feeding
  • if initiating selective serotonin reuptake inhibitor treatment in breast feeding, then fluoxetine, citalopram and escitalopram should be avoided if possible
  • when initiating antidepressant use in women who are breastfeeding, both the absolute dose and the half life should be considered
Reference:
  1. BNF (Appendix 5: Breast Feeding)
  2. NHS Specialist Pharmacy Service (January 2023). Using Selective Serotonin Reuptake Inhibitor (SSRI) antidepressants during breastfeeding
  3. NHS Specialist Pharmacy Service (January 2023). Using tricyclic antidepressants during breastfeeding
  4. SIGN (March 2012). Management of perinatal mood disorders.