Amitriptyline in Breastfeeding

Reference	Notes
Sabah Obstetrics Shared Care Guidelines (Sept 2018)	MENTAL DISORDERS IN PREGNANCY ·         Look for symptoms of postpartum psychosis / depression ·         Contraception for patient (refer to MEC) ·         Encourage breast feeding. Advise to take psychotropic medication just after breastfeeding. ·         Monitor the baby for adverse effects such as drowsiness, hypotonia, rigidity, tremor and withdrawal symptoms ·         Review family support
Uptodate: Amitriptyline	Amitriptyline and the metabolite nortriptyline are present in breast milk (Bader 1980). The relative infant dose (RID) of amitriptyline is 1.2 % when calculated using the highest breast milk concentration located and compared to a weight-adjusted maternal dose of 175 mg/day. In general, breastfeeding is considered acceptable when the RID is <10% (Anderson 2016; Ito 2000). Using the highest milk concentration (197 ng/mL), the estimated daily infant dose via breast milk is 0.03 mg/kg/day. This milk concentration was obtained following maternal administration of oral amitriptyline 175 mg/day for ~28 days (Yoshida 1997). In a review article which included six mother/infant pairs, following maternal use of amitriptyline 75 to 175 mg/day, the estimated exposure to the breastfeeding infant was calculated as 0.2% to 1.9% of the weight-adjusted maternal dose (additional detail not provided) (Fortinguerra 2009). Very small amounts of amitriptyline can be detected in the plasma and urine of breastfeeding infants (Yoshida 1997). It should be noted that actual milk concentrations of tricyclic antidepressants are generally related to maternal serum concentration and vary by fat content of breast milk; the level of detection varies greatly by assay method (Yoshida 1997). Most sources have not reported adverse events in infants exposed to amitriptyline via breast milk (Fortinguerra 2009; Larsen 2015; Yoshida 1997). However, in a case report, severe sedation with associated poor feeding was observed in a breastfed infant (~15 days old) following the initiation of amitriptyline 10 mg/day in the mother. Symptoms in the infant decreased within 24 hours and resolved within 48 hours after the maternal dose was discontinued. Once amitriptyline was reinitiated in the mother, symptoms in the infant returned (Uguz 2017). Infants of mothers using psychotropic medications should be monitored daily for changes in sleep, feeding patterns, and behavior (Bauer 2013) as well as infant growth and neurodevelopment (Sriraman 2015). Tricyclic antidepressants are not the preferred therapy for depression in breastfeeding women. However, if a TCA is needed, amitriptyline is one of the agents with information available (Larsen 2015). A woman already stabilized on a TCA during pregnancy may continue that medication while breastfeeding (Sriraman 2015). Migraine prophylaxis should be avoided in women who are breastfeeding; if needed, amitriptyline may be used if other agents are ineffective or contraindicated (Pringsheim 2012). The WHO considers amitriptyline to be compatible with breastfeeding in doses ≤150 mg/day (WHO 2002). Due to the potential for serious adverse reactions in the breastfed infant, the manufacturer recommends a decision be made whether to discontinue breastfeeding or to discontinue the drug, taking into account the importance of treatment to the mother.
https://www.drugs.com/breastfeeding/amitriptyline.html   (equivalent to LactMed)	Milk levels of amitriptyline and its metabolites are low. Immediate side effects have not been reported and a limited amount of follow-up has found no adverse effects on infant growth and development. Amitriptyline use during breastfeeding would usually not be expected to cause any adverse effects in breastfed infants, especially if the infant is older than 2 months. A safety scoring system finds amitriptyline use to be possible with caution during breastfeeding.[1] However, rare sedation has been reported in a neonate. Other agents with fewer active metabolites may be preferred when large doses are required or while nursing a newborn or preterm infant.
Maudsley 13th Edition 2018	Foetal exposure to tricyclic antidepressants (TCAs) via umbilicus and amniotic fluid is high.87,88. TCAs have been widely used throughout pregnancy without apparent detriment to the foetus.
Stahls’s Essential Psychopharmacology 2017	• Some drug is found in mother’s breast milk ✽ Recommended either to discontinue drug or bottle feed • Immediate postpartum period is a high-risk time for depression, especially in women who have had prior depressive episodes, so drug may need to be reinstituted late in the third trimester or shortly after childbirth to prevent a recurrence during the postpartum period • Must weigh benefi ts of breast feeding with risks and benefi ts of antidepressant treatment versus nontreatment to both the infant and the mother • For many patients this may mean continuing treatment during breast feeding
Briggs 2015	Amitriptyline and its active metabolites are excreted into breast milk (20–24). A recent study has measured the amount of a second active metabolite, E-10-hydroxynortriptyline, in milk (23). Serum and milk concentrations of amitriptyline in one patient were 0.14 and 0.15 mcg/mL, respectively, a milk:plasma ratio of 1.0 (20). No drug was detected in the infant’s serum. In another patient, it was estimated that the baby received about 1% of the mother’s dose (22). No clinical signs of drug activity were observed in the infant. In another study, the mother was treated with 175 mg/day of amitriptyline (23). Milk and maternal serum samples were analyzed for active drug and active metabolites on postpartum days 1–26. Amitriptyline serum levels ranged from 24 (day 1) to 71 ng/mL (days 3–26), whereas those in the milk ranged from 24 ng/mL (day 1) to only 54% of the serum levels on days 2–26. Nortriptyline serum levels ranged from 17 (day 1) to 87 ng/mL (day 26) with milk levels 74% of those in the serum. Mean concentration of the second metabolite, E-10-hydroxynortriptyline, was 127 ng/mL (days 1–26) in the serum and 70% of that in the milk. The total dose (parent drug plus metabolites) consumed by the male infant on day 26 was estimated to be 35 mcg/kg (80 times lower than the mother’s dose). The compounds were not detected in the nursing infant’s serum on day 26 and no adverse effects, including sedation, were observed in him (23). Ten nursing infants of mothers taking antidepressants (two with amitriptyline 100–175 mg/day) were compared with 15 bottle-fed infants of mothers with depression who did not breastfeed (24). Concentrations of clomipramine in fore- and hind-milk were 30 ng/mL (one patient) and 113 and 197 ng/mL (two patients), respectively. The milk:maternal plasma ratios were 0.2 and 0.9, respectively. One infant had a plasma level of 7.5 ng/mL when the mother was taking 100 mg/day. No toxic effects or delays in development were observed in the infants. The estimated daily dose consumed by the infants was about 1% of the mother’s weight-adjusted dose (24). A 1996 review of antidepressant treatment during breastfeeding found no information that amitriptyline exposure of the infant during nursing caused adverse effects (25).  Although amitriptyline and its metabolite have not been detected in infant serum, the effects of exposure to small amounts in the milk are unknown (26).

 

Accessed by J. Ho @ 29.07.2021