Citalopram in Pregnancy and Breastfeeding
      
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Citalopram (Celexa )
Antidepressant. Selective serotonin reuptake inhibitor (SSRI) . Molecular weight: 405.35.
CATEGORY: C

Citalopram is metabolized primarily to demethylcitalopram (DCT) which is approximately  one eighth as potent in the inhibition of serotonin reuptake as citalopram [1]

In reproductive animal studies, citalopram has been shown to have adverse effects on embryo/fetal and postnatal development when administered at doses greater than human therapeutic doses. Decreased embryo/fetal growth and survival and an increased incidence of fetal abnormalities (including cardiovascular and skeletal defects) were observed in the rat at a maternally toxic dose (18 times the maximum recommended human dose (MRHD) of 60 mg/day on a body surface area (mg/m 2 ) basis). In a rabbit study, no adverse effects on embryo/fetal development were observed at doses of up to approximately 5 times the MRHD [1].

In an isolated perfused human placenta model the mean transplacental transfer for citalopram and  desmethylcitalopram was found to be 9.1% and  5.6% respectively.  The presence of albumin was necessary for the transplacental transfer of citalopram [2].

Ericson and co-workers prospectively identified 365 women enrolled in The Swedish Medical Birth Registry who used citalopram during early pregnancy. Exposure to citalopram did not appear to increase the rate of major malformations above the expected baseline rate [3].

BREAST FEEDING: Citalopram is excreted into breast milk. The milk/serum concentration ratio is  1.16 to 3  [4-6]. 

Heikkinen T, et. al., prospectively compared eleven breast-feeding women taking citalopram 20 mg to 40 mg once daily with a matched control group of 10 women who were not taking medication.  Infant citalopram and metabolite plasma concentrations were found to be very low or undetectable. The neurodevelopment of all infants up to the age of 1 year was normal  [6]

Rampono J, et. al.,  as with the previous study, found very low or absent plasma concentrations of citalopram and demethylcitalopram in breast fed infants of  7 mothers taking citalopram for the treatment of depression. They estimated the mean combined dose of citalopram and demethylcitalopram  transmitted to infants via breast milk to be 4.4-5.1% as citalopram equivalents[7]. This is below the 10% notional level of concern.

Nonetheless, Nordeng and coworkers suggest that high doses of citalopram be used with caution in  breastfeeding women [8].

NEONATAL SIDE EFFECTS: Neonatal withdrawal syndrome may occur after third trimester in utero SSRI exposure. Irritability, constant crying, shivering, increased tonus, eating ,sleeping difficulties, and convulsions have been reported [9].

"Uneasy sleep" has been reported in the breast fed infant of one mother taking 40 mg/day of citalopram [10]. The usual dose of citalopram is 20 to 40 mg/day [1].

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REFERENCES


1. Physicians Desk Reference 57th ed. Montvale, NJ: Thomson PDR; 2003:1344-1345.
2.Heikkine T, et al., Transplacental transfer of citalopram, fluoxetine and their primary demethylated metabolites in isolated perfused human placenta.BJOG. 2002;109:1003-8.MEDLINE
3. Ericson A, et. al.: Delivery outcome after the use of antidepressants in early pregnancy. Eur J Clin Pharmacol 55:503-508, 1999. MEDLINE
4. Spigset O, Cet al . Excretion of citalopram in breast milk. Br J Clin Pharmacol 1997;44:295-8. MEDLINE
5. Jensen PN, et al.: Citalopram and desmethylcitalopram concentrations in breast milk and in serum of mother and infant. Ther Drug Monit 1997;19:236- 9.MEDLINE
6. Heikkinen T, et al., Citalopram in pregnancy and lactation. Clin Pharmacol Ther. 2002;72:184-91. MEDLINE
7. Rampono J, et al.: Citalopram and demethylcitalopram in human milk; distribution, excretion andeffects in breast fed infants. Br J Clin Pharmacol 2000; 50:263-8. MEDLINE
8. Nordeng H, et al., [The transfer of selective serotonin reuptake inhibitors to human milk] Tidsskr Nor Laegeforen. 2001;121:199-203. MEDLINE
9. Nordeng H, et al Neonatal withdrawal syndrome after in utero exposure to selective serotonin reuptake inhibitors. Acta Paediatr. 2001;90:288-91.MEDLINE
10. Schmidt K, et al., Citalopram and breast-feeding: serum concentration and side effects in the infant. Biol Psychiatry. 2000;47:164-5. MEDLINE

Created: 11/27/2002
Last Update: 12/2/2003

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