antidepressant treatment and breast feeding

Last edited 01/2023 and last reviewed 01/2023

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)

  • 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

SIGN (3) 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. SIGN (March 2012). Management of perinatal mood disorders.