Excretion of doxepin and N‐desmethyldoxepin in human milk.

Abstract

Doxepin and N‐desmethyldoxepin concentrations in plasma and breast milk from a lactating mother and in plasma from her infant were measured during an 8 week period using high performance liquid chromatography. Plasma concentrations ranged from 35‐68 microgram l‐1 for doxepin and 65‐131 microgram l‐1 for N‐desmethyldoxepin. Mean pre‐feed milk/plasma ratios were 1.08 and 1.02 for doxepin and N‐desmethyldoxepin respectively and increased to 1.66 and 1.53 at the post‐feed samples. Only N‐desmethyldoxepin (15 microgram l‐1) was detectable in the infant's plasma sampled after 43 days of maternal therapy.

Breast feeding and psychotropic drugs

“…Two single case studies have been published of mothers receiving daily doses of doxepin, 75 mg (Matheson et al, 1985) and 150 mg (Kemp et al, 1985). Maternal plasma concentrations of doxepin and desmethyldoxepin in the first subject (Matheson et al, 1985) went up to maxima of 15 and 57 nglml and milkplasma ratios were below 0.9 and 0.2 respectively.…”

“…The infant was observed to be pale, sweaty, drowsy and with depressed respiration, symptoms which improved following cessation of breast feeding. The mother investigated by Kemp et al (1985) was taking 150 mglday of doxepin and her plasma concentrations of the drug and its metabolite were 46 and 90 ng/ml respectively. Milk plasma ratios were about 1.1 for fore-milk and over 1.5 for hind-milk and despite the fact the infant was ingesting much bigger 'doses', neither the drug nor its metabolite were detectable in its plasma (sensitivity 5 and 15 ng/ml respectively).…”

Antidepressants and Breast-Feeding

“…[15] On the other hand, no adverse effects were noted for the breastfed infant of a mother receiving doxepin. [13] These 2 case reports illustrate the variability in response for individuals and the unreliability of making general recommendations from a limited database. Even where a drug appears to be well tolerated, vigilance is required at the beginning of treatment or when the dose is increased.…”

“…The findings have generally indicated that, despite adequate maternal serum concentrations, either the parent drug and/or its metabolites were not detected in the infant's serum, [3][4][5][6][7][8][9][10][11][12] or very low concentrations were observed. [13][14][15][16][17][18][19][20][21][22][23][24][25] Studies have measured maternal plasma and breast milk concentrations of antidepressants, demonstrating that infants would be receiving a dose, albeit low, of parent drug and its metabolites. [3,4,6,7,9,12,13,[15][16][17][19][20][21][22][23][25][26][27][28][29][30][31][32][33][34][35]…”

“…[13][14][15][16][17][18][19][20][21][22][23][24][25] Studies have measured maternal plasma and breast milk concentrations of antidepressants, demonstrating that infants would be receiving a dose, albeit low, of parent drug and its metabolites. [3,4,6,7,9,12,13,[15][16][17][19][20][21][22][23][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39] Furthermore, a few studies have examined the infants who were nursed by mothers treated with antidepressants during lactation investigating an effect, or lack of effect, of these drugs on the development of the infants. [40,41] From the available data it appears that the dose of antidepressant reaching the child is low, usually resulting in undetectable serum concentrations.…”