K. Yoshida et al., INVESTIGATION OF PHARMACOKINETICS AND OF POSSIBLE ADVERSE-EFFECTS IN INFANTS EXPOSED TO TRICYCLIC ANTIDEPRESSANTS IN BREAST-MILK, Journal of affective disorders, 43(3), 1997, pp. 225-237
We have studied ten breast-feeding mothers who were prescribed tricycl
ic antidepressant drugs and have also compared their infants' developm
ent with a similar group (n = 15) who were bottle-fed. Concentrations
of tricyclic drugs in maternal plasma and urine, in fore-milk and hind
-milk and in infant plasma (n = 6) and urine (n = 9) were measured by
gas chromatography (GC) and by an enzyme immunoassay (EIA). The fat co
ncentration in milk was also measured. Infants' health and development
were monitored by physical examination and by the Bayley Scales of In
fant Development up to 30 months. The amounts of tricyclic drugs and t
heir principal metabolites in maternal plasma were significantly corre
lated with the oral dose and with the amounts in breast-milk. Drug con
centrations in fore-milk, but not in hind-milk, increased in line with
its fat content, which was maximal in hind-milk. Correlations between
gas chromatographic and enzyme immunoassays of maternal samples were
high provided that the values for amitriptyline and nortriptyline were
excluded; immunoreactivities to these compounds were abnormally high,
suggesting that metabolites were also being measured by EIA. The dail
y doses of drugs ingested by breast-fed infants were about 1% of the m
aternal dose/kg and the immunoassay detected very small amounts of tri
cyclics in infants' plasma and urine. No acute toxic effects were foun
d in the ten medicated breast-fed infants and there was no evidence of
developmental delays in comparison with bottle-fed infants. Although
the number of subjects in this study is small, when taken in conjuncti
on with other published findings, we have not found any reason to prev
ent mothers who are taking established tricyclic antidepressants from
breast-feeding their babies if they want to do so. (C) 1997 Elsevier S
cience B.V.