Paroxetine during lactation: is it really safe for the infant?

Sir, Paroxetine, a selective serotonin re-uptake inhibitor (SSRI), is frequently used to treat mothers with postnatal depression (1). In a recent overview about drugs and lactation, it was concluded that, in children of mothers on paroxetine, no adverse effects on the child’s health had been reported (2). However, drugs which do affect the function of the adult nervous system can be considered as potential behavioural teratogens for the young developing nervous system (3). Serotonin is a neurotransmitter and neuromodulator, and plays an important role during brain development (4). Newborns prenatally exposed to SSRIs show abnormal neurobehaviour (5). To review the evidence of safety of paroxetine during breastfeeding, we searched Medline, the Cochrane Library of Controlled Trials and SumSearch, and browsed the references from the retrieved articles for further articles. Eight articles concerning lactation and paroxetine were found (6–13). Seventy-seven lactating mothers participated in the eight studies. The median dose of paroxetine prescribed was 20 mg (range 10–50 mg). In one article, the use of psychoactive co-medication was mentioned in 11 mothers (10). Maternal serum levels were determined 164 times, occasionally at various times in the same mother. No correlation between maternal dose, maternal body weight and serum levels was found (10). Opinions vary on the time of occurrence of peak levels: 2 to 4 h or 5 to 7 h after ingestion (7, 9). A correlation between the levels of paroxetine in maternal serum and breast milk was found, and the computed mean plasma/ milk ratio ranged from 0.3–2.0 (7, 9). The highest levels of paroxetine, a fat-soluble drug, were found in hind milk, which contains relatively more fat (8). Blood samples were taken in 40 children, and only in one sample could paroxetine be detected; but the timing of the infant blood sampling was not adjusted to the time the mother took the medication. The mothers did not report any adverse effects of paroxetine on the infant. Formal paediatric examinations were not performed. Recently, 27 breastfed children of mothers on paroxetine were compared with controls with respect to weight gain and developmental milestones. No differences were found (14). From these studies, we know that maternally ingested paroxetine is excreted in breast milk and maternal serum levels correlate with breast milk levels. Paroxetine was not demonstrated in the infant’s blood, but the time of occurrence of the peak levels in the milk were not taken into account. Generally, fat-soluble medications reach levels in the cerebrospinal fluid which are 10 to 30 times higher than those in serum (15). This means that it is still unknown whether maternally ingested paroxetine reaches the infant’s brain. The fact that up ntil now no adverse effects of paroxetine on the infant have been reported can be attributed to the relatively crude methods of infant investigation. Whether negative effects on the child’s brain occur has yet to be determined. One possible method could be to assess the quality of general movements (GMs). Mildly abnormal GMs can be attributed to dysfunction of the monoaminergic systems (16). Is paroxetine safe during lactation? It probably is, but to be sure, a normal outcome of appropriate neurological and psychological development of exposed children should be demonstrated.