Lifelong Effects of infant SSRI exposure via breastmilk

[Bitty360]

Is there any information available regarding long-term effects (into adulthood) of infant exposure to SSRIs via breastmilk? I know Zoloft is L2 and is the preferred antidepressants for a breastfeeding mother and is generally found in very low levels in milk. I'm wondering, though, if the exposure to the drug could change the infant's brain chemistry or in some way predispose him/her to depression later in life.

Thanks for your time and attention.

[Sandra]

Bitty360,
Zoloft is now rated an L1-extensive data-compatible. The amount transferred into breast milk is only 0.4-2.2% of your dose.The data is consistent that levels in milk are quite low and do not normally affect an infant. Monitor for sedation or irritability, not waking to feed/poor feeding and weight gain. Unfortunately we do not have any long term data on this medication at this time. Here is the data we do have.

Sertraline is a typical serotonin reuptake inhibitor similar to fluoxetine; however, the longer half-life metabolite of sertraline, desmethylsertraline, is only marginally active. In one study of a single patient taking 100 mg of sertraline daily for 3 weeks postpartum, the concentration of sertraline in milk was 24, 43, 40, and 19 micrograms per Liter of milk at 1, 5, 9, and 23 hours, respectively following the dose.[1] The maternal plasma levels of sertraline after 12 hours was 48 ng/mL. Sertraline plasma levels in the infant at three weeks were below the limit of detection (<0.5 ng/mL) at 12 hours post-dose. Routine pediatric evaluation after 3 months revealed a neonate of normal weight who had achieved the appropriate developmental milestones.

In another study of 3 breastfeeding patients who received 50-100 mg sertraline daily, the maternal plasma levels ranged from 18.4 to 95.8 ng/mL, whereas the plasma levels of sertraline and its metabolite, desmethylsertraline, in the 3 breastfed infants were below the limit of detection (<2 ng/mL).[2] Milk levels were not measured.

Another recent publication reviewed the changes in platelet serotonin levels in breastfeeding mothers and their infants who received up to 100 mg of sertraline daily.[3] Mothers treated with sertraline had significant decreases in their platelet serotonin levels, which is expected. However, there was no change in platelet serotonin levels in breastfed infants of mothers consuming sertraline, suggesting that only minimal amounts of sertraline are actually transferred to the infant. This confirms other studies. Studies by Stowe of 11 mother/infant pairs (maternal dose= 25-150 mg/day) further suggest minimal transfer of sertraline into human milk.[4] From this good study, the concentration of sertraline peaked in the milk at 7-8 hours and the metabolite (desmethylsertraline) at 5-11 hours. The reported concentrations of sertraline and desmethylsertraline in breastmilk were 17-173 microgram/L and 22-294 microgram/L respectively. The reported dose of sertraline to the infant via milk varied from undetectable (5 of 11) to 0.124 mg/day in one infant. The infant's serum concentration of sertraline varied from undetectable to 3 ng/mL but was undetectable in 7 of 11 patients. No developmental abnormalities were noted in any of the infants studied.

In a study of 8 women taking sertraline (1.05 mg/kg/day) the mean milk/plasma ratio was 1.93 and 1.64 for sertraline and N-desmethylsertraline.[5] Infant exposure estimated from actual milk produced was 0.2% and 0.3% of the weight-adjusted maternal dose for sertraline and N-desmethylsertraline (sertraline equivalents) respectively. Assuming a 150 mL/kg/day intake, infant exposure was significantly greater at 0.9% and 1.32% for sertraline and N-desmethylsertraline respectively. Neither sertraline nor its N-desmethyl metabolite could be detected in plasma samples from the four infants tested. No adverse effects were observed in any of the eight infants and all had achieved normal developmental milestones.

Sertraline is a potent inhibitor of 5-HT transporter function both in the CNS and platelets. One recent study assessed the effect of sertraline on platelet 5-HT transporter function in 14 breastfeeding mothers (25-200 mg/day) and their infants to determine if even low levels of sertraline exposure could perhaps lead to changes in the infant's blood platelet 5-HT levels and, therefore, CNS serotonin levels.[6] While a significant reduction in platelet levels of 5-HT were noted in the mothers, no changes in 5-HT levels were noted in the 14 infants. Thus, it appears that at typical clinical doses, maternal sertraline has a minimal effect on platelet 5-HT transport in breastfeeding infants.

These studies generally confirm that the transfer of sertraline and its metabolite to the infant is minimal, and that attaining clinically relevant plasma levels in infants is remote at maternal doses less than 150 mg/day. Thorough reviews of antidepressant use in breastfeeding mothers are available.[7-9]

A 2015 review of sertraline levels in breastfed infants confirmed that drug levels in breastmilk are low.[10] This review reported that of 167 infant sertraline levels, 146 (87%) were undetectable and of 150 desmethylsertraline levels, 105 (70%) were undetectable. The authors of this analysis reported that no adverse events occurred in the 167 infants, even in those with detectable levels (median 5 ng/mL for both sertraline and its metabolite).

1.##Altshuler LL, Burt VK, McMullen M, Hendrick V. Breastfeeding and sertraline: a 24-hour analysis. J Clin Psychiatry 1995; 56(6):243-245.
2.##Mammen OK, Perel JM, Rudolph G, Foglia JP, Wheeler SB. Sertraline and norsertraline levels in three breastfed infants. J Clin Psychiatry 1997; 58(3):100-103.
3.##Epperson CN. et.al. Sertraine and Breastfeeding. NEJM 1997; 336(16):1189-1190.
4.##Stowe ZN, Owens MJ, Landry JC, Kilts CD, Ely T, Llewellyn A, Nemeroff CB. Sertraline and desmethylsertraline in human breast milk and nursing infants. Am J Psychiatry 1997; 154(9):1255-1260.
5.##Kristensen JH, Ilett KF, Dusci LJ, Hackett LP, Yapp P, Wojnar-Horton RE, Roberts MJ, Paech M. Distribution and excretion of sertraline and N-desmethylsertraline in human milk. Br J Clin Pharmacol 1998; 45(5):453-457.
6.##Epperson N, Czarkowski KA, Ward-O'Brien D, Weiss E, Gueorguieva R, Jatlow P, Anderson GM. Maternal sertraline treatment and serotonin transport in breast-feeding mother-infant pairs. Am J Psychiatry 2001; 158(10):1631-1637.
7.##Wisner KL, Perel JM, Findling RL. Antidepressant treatment during breast-feeding. Am J Psychiatry 1996; 153(9):1132-1137.
8.##Stowe ZN, Hostetter AL, Owens MJ, Ritchie JC, Sternberg K, Cohen LS, Nemeroff CB. The pharmacokinetics of sertraline excretion into human brest milk: determinants of infant serum concentrations. J Clin Psychiatry 2003; 64(1):73-80.
9.##Weissman AM, Levy BT, Hartz AJ, et.al. Pooled Analysis of Antidepressant Levels in Lactating Mothers, Breast Milk, and Nursing Infants. Am J Psychiatry 2004 June; 161(6):1066-1078.
10.##Pinheiro W, Bogen DL, Hoxha D et al. Sertraline and breastfeeding: review and meta-analysis. Arch Womens Ment Health 2015;18:139-46.
11.##Rohan A, Symonston A. Drug distribution in human milk. Aust Prescriber 1997;20:84.

I hope this helps. Please call the InfantRisk Center if you have any other questions at 806-352-2519. Thanks,

Sandra Lovato R.N.
InfantRisk Center