What is the pKa-value of sertraline and could you give sertraline to a breast-feeding woman without

Fråga: What is the pKa-value of sertraline and could you give sertraline to a breast-feeding woman without affecting the child? A woman treated with Zoloft (sertraline), 50 mg/day, is still breast feeding her 1.5 year old child.

Sammanfattning: Sertraline appears to be one of the drugs that could be given to a breast-feeding mother with no or very little effect on the infant. However, as the metabolite of sertraline, desmethylsertraline, was found in the infant´s serum and higher than the mother compound underscore the need to determine drug metabolite concentrations. Special precaution should be made when prescribing a breast-feeding mother antidepressants and is always a case-specific risk-benefit decision.

Svar: Sertraline belongs to the SSRI group of antidepressants. The pKa of sertraline is 8.9 (1).

According to a review article (2), where 15 published reports were critically analysed for nine antidepressants, sertraline was one of the drugs (including amitriptylin, nortriptyline, desipramine, clomipramine and dothiepin) in which quantifiable amounts were not found in nurslings and no adverse effects were reported. In the same article it was stated that doxepin and fluoxetine are not drugs of choice due to adverse effects seen in the nurslings. It was also suggested that infants more than 10 weeks of age are at low risk for adverse effects from tricyclics in infant serum and that mother-baby pair should be monitored.

In FASS (3) it is stated that fluoxetine passes over to human milk and that the amount of the drug in milk may affect the child during nursing. In a later paper (4) by Wisner et al it was concluded that most breast-fed infants whose mothers were taking sertraline had very low serum levels of both sertraline and the metabolite N-desmethyl-sertraline. In a study (5) of 11 mother-infant pairs the serum levels 24 hours after a dose and the infants´ serum levels of sertraline 2-4 hours after nursing were measured. The maternal medication doses were between 25-150 mg/day and the infant´s dose were calculated to 0.019-0.124 mg/day. The infant´s serum levels of sertraline were 2.7-3.0 ng/ml in three cases and not detectable in the rest. The maternal serum concentrations were measured to 8-92 ng/ml. The serum levels of the metabolite desmethylsertraline ranged between not detectable to 10.0 ng/ml and the maternal serum concentration between 15-212 ng/ml. It was shown that increasing the maternal daily dose increased the breast milk concentration of both sertraline and desmethylsertraline. It was also shown that the concentrations in breast milk of sertraline and desmethylsertraline showed the highest concentrations 7-9 hours after the last maternal dose and that the infant´s daily dose could be reduced with approximately 25 per cent by discarding a single feeding during that specific time.

Serotonin modulates synaptogenesis and early neurodevelopment in neonatals. Sertraline as a reuptake inhibitor could thus cause central and peripheral blockade in an infant. Epperson et al (6) showed in a letter that sertraline affects the serotonin transporters (identical transporters in platelets and neurons) and that the levels of platelet serotonin decreased in the mothers after treatment with sertraline but little or no change was seen in the levels in the 4 nursling infants exposed to sertraline through breast milk.