Tuija Heikkinen1, Ulla Ekblad, Pentti Kero, Satu Ekblad, Kari Laine. 1. Department of Pharmacology and Clinical Pharmacology, University Central Hospital, University of Turku, Itäinen Pitkäkatu 4, FIN-20520 Turku, Finland. tuija.heikkinen@utu.fi
Abstract
BACKGROUND: Although citalopram has gained wide acceptance in the treatment of depression and anxiety disorders, its use during pregnancy and lactation has been poorly characterized. The aim of this study was to examine the efficacy and safety of citalopram in relation to concentrations of citalopram and its metabolites during pregnancy and lactation. METHODS: Eleven mothers taking citalopram and their infants were enrolled in the study, and a control group of 10 women who were not taking medication were prospectively matched for confounding obstetric characteristics at the time of delivery. Plasma and breast milk samples were collected from mother/infant pairs during pregnancy, at delivery, and for up to 2 months after delivery. Trough plasma and breast milk concentrations of citalopram, desmethylcitalopram, and didesmethylcitalopram were measured by HPLC. The pregnancy outcome was recorded, and the neurodevelopment of children was monitored for up to 1 year. RESULTS: Although the citalopram dose of 20 mg to 40 mg once daily resulted in low maternal trough plasma concentrations (range, 46-214 nmol/L) and metabolites during pregnancy, only one subject required an increase of daily dose. The mean didesmethylcitalopram-desmethylcitalopram metabolic ratio was significantly higher during pregnancy (54%, P <.001) than at 2 months after delivery, indicating induction of cytochrome P450 (CYP) 2D6 during pregnancy. At delivery, the trough plasma citalopram, desmethylcitalopram, and didesmethylcitalopram concentrations in the infants were 64%, 66%, and 68% of the maternal concentrations, respectively. The citalopram and metabolite concentrations in the milk were 2- to 3-fold higher compared with maternal plasma concentrations, but the infant citalopram and metabolite plasma concentrations were very low or undetectable. The delivery outcome and the neurodevelopment of all infants up to the age of 1 year were normal. CONCLUSION: Even though the sample size was limited, results from this prospective clinical trial suggest uncomplicated pregnancy outcome in mothers using citalopram during pregnancy and minimal exposure of the infants to citalopram during lactation. However, maternal therapeutic drug monitoring of citalopram should be recommended to minimize fetal exposure.
BACKGROUND: Although citalopram has gained wide acceptance in the treatment of depression and anxiety disorders, its use during pregnancy and lactation has been poorly characterized. The aim of this study was to examine the efficacy and safety of citalopram in relation to concentrations of citalopram and its metabolites during pregnancy and lactation. METHODS: Eleven mothers taking citalopram and their infants were enrolled in the study, and a control group of 10 women who were not taking medication were prospectively matched for confounding obstetric characteristics at the time of delivery. Plasma and breast milk samples were collected from mother/infant pairs during pregnancy, at delivery, and for up to 2 months after delivery. Trough plasma and breast milk concentrations of citalopram, desmethylcitalopram, and didesmethylcitalopram were measured by HPLC. The pregnancy outcome was recorded, and the neurodevelopment of children was monitored for up to 1 year. RESULTS: Although the citalopram dose of 20 mg to 40 mg once daily resulted in low maternal trough plasma concentrations (range, 46-214 nmol/L) and metabolites during pregnancy, only one subject required an increase of daily dose. The mean didesmethylcitalopram-desmethylcitalopram metabolic ratio was significantly higher during pregnancy (54%, P <.001) than at 2 months after delivery, indicating induction of cytochrome P450 (CYP) 2D6 during pregnancy. At delivery, the trough plasma citalopram, desmethylcitalopram, and didesmethylcitalopram concentrations in the infants were 64%, 66%, and 68% of the maternal concentrations, respectively. The citalopram and metabolite concentrations in the milk were 2- to 3-fold higher compared with maternal plasma concentrations, but the infantcitalopram and metabolite plasma concentrations were very low or undetectable. The delivery outcome and the neurodevelopment of all infants up to the age of 1 year were normal. CONCLUSION: Even though the sample size was limited, results from this prospective clinical trial suggest uncomplicated pregnancy outcome in mothers using citalopram during pregnancy and minimal exposure of the infants to citalopram during lactation. However, maternal therapeutic drug monitoring of citalopram should be recommended to minimize fetal exposure.