Developmental Toxicology Studies of Fluoxetine Hydrochloride Administered Orally to Rats and Rabbits

Decreased noradrenergic and serotonergic reactivity of vas deferens of newborn rats from mothers treated with the serotonin reuptake inhibitor fluoxetine during pregnancy and breast-feeding

“…A decrease of body weight by fluoxetine, as here shown, has been described in humans (Halford et al, 2005) and animals (Benfield et al, 1986;Byrd and Markham, 1994;Da-Silva et al, 1999). Besides lower weights, the newborn whose mothers received fluoxetine during pregnancy had also lower stature, compared with controls (Chambers et al, 1999).…”

Long-term effects of fluoxetine or vehicle administration during pregnancy on behavioral outcomes in guinea pig offspring

“…Weights at birth of human infants exposed prenatally to fluoxetine have been reported to be unchanged in most studies (Cohen et al 2000;Nulman et al 2002;Oberlander et al 2002;Casper et al 2003;Heikkinen et al 2003;Laine et al 2003), or reduced with high dose (40-80 mg per day) or third trimester exposure (Chambers et al 1996;Hendrick et al 2003b). In rat studies, maternal weight gain has been reported to be reduced only with fluoxetine doses >12 mg/kg per day (Byrd and Markham 1994;Vorhees et al 1994;da-Silva et al 1999). Lower doses of prenatal fluoxetine (8-10 mg/kg per day) have been reported to reduce birth weight in the neonatal rat, but these effects did not persist into adulthood except in the study by Cabrera and Battaglia (Cabrera and Battaglia 1994;Vorhees et al 1994;da-Silva et al 1999).…”

Long-Term Outcomes of Developmental Exposure to Fluoxetine: A Review of the Animal Literature

“…Oddly, the high mortality rate noted in this study, despite resulting from a very low maternal dosage (0.8 mg/kg/day, i.p. ), has not been consistently replicated in numerous other studies using much larger doses over a similar period of time during development [21,22,23]. Together, these findings suggest that such a small dose only has a pronounced effect when administered by intraperitoneal injection, and more broadly, that increased mortality might result only from exposure during a critical period in development, perhaps organogenesis, though it should be noted that some researchers who reported no change in mortality began administration as early as the sixth gestational day [21,23].…”

“…), has not been consistently replicated in numerous other studies using much larger doses over a similar period of time during development [21,22,23]. Together, these findings suggest that such a small dose only has a pronounced effect when administered by intraperitoneal injection, and more broadly, that increased mortality might result only from exposure during a critical period in development, perhaps organogenesis, though it should be noted that some researchers who reported no change in mortality began administration as early as the sixth gestational day [21,23]. In addition to cardiac malformations, minor abnormalities and developmental delays have also been noted in FLX-exposed rats, such as transient impairment of the negative geotaxis reflex and delayed eruption of the incisor teeth [23], as well as an increase in the rate of ultrasonic vocalizations [24].…”