General considerations

It is important to complete an individual risk assessment for your patient and to apply the principles of prescribing in breastfeeding when looking at the available information and making treatment decisions.

Recommendation

Imipramine and nortriptyline are the tricyclic antidepressants (TCAs) of choice during breastfeeding. This is because they are less sedating, therefore reducing the risk of infant sedation.

However, most TCAs can be used during breastfeeding if clinically appropriate.

Limited evidence shows milk levels are very low. In addition, 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. This could result in accumulation and increased risk of side-effects due to an infant’s underdeveloped clearance capacity, particularly in the neonatal period. However, in the majority of infants exposed in published studies, no side-effects were reported.

Limited data show encouraging outcomes when considering longer term effects on infants exposed to TCAs through breast milk.

Recommendations apply to any indication the TCA is being used for, such as neuropathic pain.

Clinical considerations

Untreated or inadequately treated depression can have adverse effects on the mother and infant and it is important that the mother receives effective treatment and does not stop taking it suddenly.

Treatment choice should primarily focus on controlling the mother’s symptoms. Safety in breastfeeding is a secondary consideration.

There is no need to change a TCA used successfully during pregnancy to a preferred choice in breastfeeding as long as the infant has been born full term and healthy.

Discontinuation syndrome

TCAs can cause discontinuation symptoms if stopped abruptly. This may make it more difficult for a breastfeeding mother to stop treatment, and should be considered when making medicine choices.

Neonatal withdrawal syndrome

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.

It 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

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.

Specific recommendations

Patient Information

The NHS website provides advice for patients on the use of specific antidepressants in breastfeeding.

Contact us

Get in touch with the UK Drugs In Lactation Advisory Service (UKDILAS), our specialist breastfeeding medicines advice service if you need support in the following situations:

• you need further advice
• the antidepressant in question is not included in our advice
• the infant is unwell or premature
• multiple medicines are being taken

About our recommendations

Recommendations are based on published evidence where available. However, evidence is generally very poor and limited, and can require professional interpretation. Assessments are often based on reviewing case reports which can be conflicting and lack detail.

If there is no published clinical evidence, assessments are based on: pharmacodynamic and pharmacokinetic principles, extrapolation from similar drugs, risk assessment of normal clinical use, expert advice, and unpublished data. Simulated data is now increasingly being used due to the ethical difficulties around gathering good quality evidence in this area.

Bibliography

Full referencing is available on request.