Is Fluoxetine safe while breastfeeding?

Effects on the breastfed infant

Colic, decreased sleep, vomiting and watery stools occurred in a 6-day-old breastfed infant probably caused by maternal fluoxetine.[ 16 ] Two other reports of colic in breastfed infants, a 1.76-month-old and a 2-month-old, were possibly caused by fluoxetine in breastmilk. The older of the two also exhibited hyperactivity.[ 9 ] Another case of possible increased irritability in a 3-month-old was noted by a pediatrician observer, who was the infant s father. However, the mother and the infant s pediatrician disagreed.[ 20 ] Occurrence of hyperglycemia and glycosuria in a 5-month-old, possibly from fluoxetine in breastmilk was reported to the Australian Adverse Drug Reaction Advisory Committee.[ 21 ] A 3-day-old breastfed infant was difficult to arouse, ceased rooting behavior, decreased nursing, and was moaning and grunting. Although the infant had been exposed in utero and was somewhat drowsy during the first 2 days of life, symptoms became worse after the mother's milk came in on day 3. These effects were probably caused by fluoxetine in breastmilk.[ 17 ] Possible drug-induced seizure-like activity and cyanosis occurred in a breastfed 3-week-old breastfed infant whose mother was taking fluoxetine, carbamazepine and buspirone during pregnancy and breastfeeding.[ 22 ] One observational report of 4 infants found no apparent neurological abnormalities following exposure to fluoxetine in milk for 12 to 52 weeks.[ 23 ] A retrospective, case-control, cohort study compared the weights of the infants of mothers who took fluoxetine during pregnancy and breastfed for at least 2 weeks postpartum to the infants of mothers who took fluoxetine during pregnancy and did not breastfeed. Compared to controls, decreased weight gain occurred among the 26 infants exposed postpartum to fluoxetine in breastmilk, although the weights were still in the normal range.[ 24 ] A prospective study of 51 nursing women taking fluoxetine and 63 nursing women who took no fluoxetine found no effect on

Effects on milk supply

Fluoxetine has caused increased prolactin levels and galactorrhea in nonpregnant, nonnursing patients.[ 38 - 46 ] Euprolactinemic galactorrhea has also been reported.[ 47 ] In a study of cases of hyperprolactinemia and its symptoms (e.g., gynecomastia) reported to a French pharmacovigilance center, fluoxetine was found to have a 3.6-fold increased risk of causing hyperprolactinemia compared to other drugs.[ 42 ] Preliminary animal and in vitro studies found that fluoxetine may have some estrogenic activity.[ 43 ] The prolactin level in a mother with established lactation may not affect her ability to breastfeed. In a small prospective study, 8 primiparous women who were taking a serotonin reuptake inhibitor (SRI; 3 taking fluoxetine and 1 each taking citalopram, duloxetine, escitalopram, paroxetine or sertraline) were compared to 423 mothers who were not taking an SRI. Mothers taking an SRI had an onset of milk secretory activation (lactogenesis II) that was delayed by an average of 16.7 hours compared to controls (85.8 hours postpartum in the SRI-treated mothers and 69.1 h in the untreated mothers), which doubled the risk of delayed feeding behavior compared to the untreated group. However, the delay in lactogenesis II may not be clinically important, since there was no statistically significant difference between the groups in the percentage of mothers experiencing feeding difficulties after day 4 postpartum.[ 44 ] A case control study compared the rate of predominant breastfeeding at 2 weeks postpartum in mothers who took an SSRI antidepressant throughout pregnancy and at delivery (n = 167) or an SSRI during pregnancy only (n = 117) to a control group of mothers who took no antidepressants (n = 182). Among the two groups who had taken an SSRI, 33 took citalopram, 18 took escitalopram, 63 took fluoxetine, 2 took fluvoxamine, 78 took paroxetine, and 87 took sertraline. Among the women who took an SSRI, the breastfeeding rate at 2 weeks postpartum was 27% to 33% low

Levels in milk

Fluoxetine is metabolized to norfluoxetine which has antidepressant activity that is considered to be equal to fluoxetine.[ 2 ] Maternal Levels. In a pooled analysis of serum levels from published studies and 1 unpublished case, the authors found that 20 mothers taking an average daily dosage of 28 mg (range 10 to 80 mg) had an average milk fluoxetine level of 76 mcg/L (range 23 to 189 mcg/L).[ 4 ] Using the average dosage and milk level data from this paper, an exclusively breastfed infant would receive an estimated 2.4% of the maternal weight-adjusted dosage of fluoxetine; however, the substantial contribution of norfluoxetine was not considered. In one of the studies included in the pooled analysis that measured both fluoxetine and norfluoxetine in 14 mothers, the average daily infant dosage in breastmilk was about 7% (range 3 to 12%) of the mother's weight-adjusted dosage.[ 4 ] Eleven women taking fluoxetine 20 to 40 mg daily during pregnancy and lactation had trough milk fluoxetine and norfluoxetine levels measured on day 4, week 2 and month 2 postpartum. When standardized to a 20 mg daily dosage, total drug concentration in breastmilk ranged from 75.4 to 91.5 mcg/L at the 3 times. The authors estimated that an exclusively breastfed infant would receive a minimum of 2.4% and 3.8% of the maternal weight-adjusted dosage of the drug and metabolite combined with this maternal dosage regimen at 2 weeks and 2 months of age, respectively.[ 5 ] In 1 mother who was 11 weeks postpartum and taking fluoxetine in a daily dosage of 20 mg, the authors estimated that an exclusively breastfed infant would receive 3.3% of the maternal weight-adjusted dosage.[ 6 ] At 2 months postpartum, 7 mothers taking an average of 24 mg of fluoxetine daily had average breastmilk levels of 63.7 mcg/L of fluoxetine and 103.8 mcg/L of norfluoxetine. These data indicate that a fully breastfed infant would receive 25 mcg/kg daily of fluoxetine plus norfluoxetine. This value would be about 6.3% of

Alternatives LactMed lists

• Nortriptyline
• Paroxetine
• Sertraline