Citalopram use while Breastfeeding

Drugs containing Citalopram: Celexa

Citalopram Levels and Effects while Breastfeeding

Summary of Use during Lactation

Infants receive citalopram in breastmilk and it is detectable in low levels in the serum of some. The dosage that the infant receives and serum level achieved are probably related to the genetic metabolic capacity of the mother and infant. A few cases of minor behavioral side effects such as drowsiness or fussiness have been reported, but no adverse effects on development have been found in infants followed for up to a year.

If citalopram is required by the mother, it is not a reason to discontinue breastfeeding. If the mother was taking citalopram during pregnancy or if other antidepressants have been ineffective, most experts recommend against changing medications during breastfeeding. Otherwise, agents with lower excretion into breastmilk may be preferred, especially while nursing a newborn or preterm infant. The S-isomer of citalopram, escitalopram, has a usual dosage of escitalopram of about 25% that of citalopram, infant exposure is lower, and adverse reactions appear less likely. Escitalopram therefore may be preferred over citalopram during breastfeeding. The breastfed infant should be monitored for behavioral side effects such as sedation or fussiness. Mothers taking an SSRI during pregnancy and postpartum may have more difficulty breastfeeding and may need additional breastfeeding support.

Drug Levels

Citalopram is metabolized to 2 metabolites, each having antidepressant activity considered to be 13% that of citalopram.[1]

Maternal Levels In a pooled analysis of serum levels from published studies and 2 unpublished cases, the authors found that 18 mothers taking an average daily dosage of 29 mg (range 20 to 60 mg) had an average milk citalopram level of 157 mcg/L (range 41 to 451 mcg/L).[1] Using the average dosage and milk level data from this paper, an exclusively breastfed infant would receive an estimated 7.9% of the maternal weight-adjusted dosage of citalopram.

In 9 mothers taking citalopram 20 to 40 mg daily while breastfeeding, trough milk samples were taken immediately before nursing on the morning of day 4, and during week 2 and month 2 postpartum. Citalopram milk trough concentrations standardized to a dosage of 20 mg daily averaged 81.4, 103.4 and 75.9 mcg/L at the 3 sampling times. The authors reported that an exclusively breastfed infant would receive an estimated minimum of 0.3 and 0.2 % of the maternal weight-adjusted dosage of citalopram at 2 weeks and 2 months postpartum, respectively.[2] However, these values appear to be the result of a calculation error. Using the milk concentration values above, one can calculate a minimum infant dosage of 4.7 and 3.4% of the weight-adjusted maternal dosage which is consistent with values reported in other studies.

In 10 breastfed (extent not stated) infants (including one pair of twins) aged 3 to 42 weeks whose mothers were taking an average daily dosage of 24 mg (range 20 to 50 mg) of citalopram, the authors calculated that their fully breastfed infants would receive an average of 5.2% (range 2.5 to 9.4%) of the maternal dosage.[3]

A mother was taking oral citalopram 40 mg once daily in the evening. Single milk samples were obtained 16 hours after the dose on days 25, 46 and 53 postpartum. Milk citalopram levels were 280, 230 and 320 mcg/L. These values represent 5.8%, 4.7% and 6.6% of the maternal weight-adjusted dosage.[4]

Infant Levels In a pooled analysis of 5 mother-infant pairs from published and unpublished cases, the authors found that infants had an average of 7% of their mothers' citalopram plasma levels; 1 of the 5 infants had a plasma level greater than 10% of the mother's plasma level which was defined by the authors as being elevated.[1]

The breastfed infants of 9 mothers who took citalopram during pregnancy and postpartum had serum citalopram levels that were 63% of maternal serum levels at delivery. The infants' serum levels fell by 37% by day 2, 61% by day 4, and 90% by week 2, despite exclusive breastfeeding. At 2 months of age, infant citalopram serum levels were about 2% of those of the mother; metabolite serum levels were somewhat higher.[2]

In 10 breastfed (extent not stated) infants aged 3 to 42 weeks whose mothers were taking citalopram in an average daily dosage of 24 mg (range 20 to 50 mg), citalopram was detected in 6 of the infants. The serum drug levels of the 10 infants averaged 0.9% (range 0 to 4.8%) of those of their mothers. Two of the infants with detectable citalopram were twins whose mother was a poor metabolizer of citalopram (CYP2C19*2 mutation). Five infants with the CYP2C19*1/*2 genotype had serum levels that were 3.75 times higher than the other 5 infants with the CYP2C19*1/*1 genotype.[3]

A mother was taking oral citalopram 40 mg once daily at 11 pm. Infant serum levels were measured at 12, 25 and 53 days of age, the first at an unspecified time and the latter two at 3 pm. Infant citalopram serum levels were 2.3, 1.2 and 1.7 mcg/L at these times. The infant serum levels on days 25 and 53 represented 0.9% and 1.8% of the mothers serum levels, respectively.[4]

Effects in Breastfed Infants

The manufacturer states that drowsiness and weight loss in breastfed infants has occurred.

Uneasy sleep that reversed with dosage reduction and partial formula supplementation was probably caused by citalopram in breastmilk in a 5-month-old infant.[5]

A group of 10 infants breastfed (6 exclusive, 3 received some formula beginning at 2 months) from birth to one year during maternal citalopram use had normal body weight and neurological development in all infants compared to 9 control infants whose mothers did not take citalopram.[2]

Three mothers who took an average citalopram dose of 15 mg once daily breastfed their infants exclusively for 4 months and at least 50% during months 5 and 6. Their infants had 6-month weight gains that were normal according to national growth standards.[6]

A study compared adverse reactions in 31 infants breastfed during maternal citalopram use to a control group of 31 breastfed infants whose mothers did not take an antidepressant. There were numerically more adverse events reported in the citalopram group (3 vs 1). However, the study found no statistical difference in the rate of adverse effects between the groups of infants and none of the side effects was serious. One mother reported infant irritability and restlessness after she began citalopram at 2 months postpartum. The side effects subsided after she stopped breastfeeding 2 weeks later.[7]

In 10 breastfed (extent not stated) infants aged 3 to 42 weeks whose mothers were taking citalopram an average of 24 mg daily, no short-term adverse reactions were noted clinically at the time of the study.[3]

A breastfed infant whose mother took citalopram 40 mg daily throughout pregnancy and postpartum had numerous symptoms such as superficial and irregular breathing, apnea, disordered sleep and hypotonia after birth. All symptoms disappeared by 3 weeks of age. Symptoms were judged to likely be withdrawal symptoms rather than side effects of the drug in the breastmilk.[4]

A woman was restarted on citalopram 10 mg daily after having stopped the drug for the last month of pregnancy. Her infant breastfed for 6 months (extent not stated). The infant had no perinatal complications, and the infant's pediatrician noted no neuropsychological abnormalities at 18 months of age.[8]

A woman took citalopram 60 mg and ziprasidone 40 mg daily throughout pregnancy and postpartum. She breastfed extensively, except for occasional formula feedings by others. At 6 months of age, a pediatrician found the infant to be healthy with normal growth and development.[9]

An uncontrolled online survey compiled data on 930 mothers who nursed their infants while taking an antidepressant. Infant drug discontinuation symptoms (e.g., irritability, low body temperature, uncontrollable crying, eating and sleeping disorders) were reported in about 10% of infants. Mothers who took antidepressants only during breastfeeding were much less likely to notice symptoms of drug discontinuation in their infants than those who took the drug in pregnancy and lactation.[10]

Effects on Lactation and Breastmilk

The SSRI class of drugs, including citalopram, can cause increased prolactin levels and galactorrhea in nonpregnant, nonnursing patients.[11][12][13][14] In a study of cases of hyperprolactinemia and its symptoms (e.g., gynecomastia) reported to a French pharmacovigilance center, fluvoxamine was found to have a 3.9-fold increased risk of causing hyperprolactinemia compared to other drugs.[15] 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.[16]

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% lower than mother who did not take antidepressants, with no statistical difference in breastfeeding rates between the SSRI-exposed groups.[17]

Alternate Drugs to Consider

Escitalopram, Nortriptyline, Paroxetine, Sertraline

References

1. Weissman AM, Levy BT, Hartz AJ et al. Pooled analysis of antidepressant levels in lactating mothers, breast milk, and nursing infants. Am J Psychiatry. 2004;161:1066-78. PMID: 15169695

2. Heikkinen T, Ekblad U, Kero P et al. Citalopram in pregnancy and lactation. Clin Pharmacol Ther. 2002;72:184-91. PMID: 12189365

3. Berle JO, Steen VM, Aamo TO et al. Breastfeeding during maternal antidepressant treatment with serotonin reuptake inhibitors: infant exposure, clinical symptoms, and cytochrome P450 genotypes. J Clin Psychiatry. 2004;65:1228-34. PMID: 15367050

4. Franssen EJ, Meijs V, Ettaher F et al. Citalopram serum and milk levels in mother and infant during lactation. Ther Drug Monit. 2006;28:2-4. PMID: 16418683

5. Schmidt K, Oleson OV, Jensen PN. Citalopram and breast-feeding: serum concentration and side effects in the infant. Biol Psychiatry. 2000;47:164-5. PMID: 10664835

6. Hendrick V, Smith LM, Hwang S et al. Weight gain in breastfed infants of mothers taking antidepressant medications. J Clin Psychiatry. 2003;64:410-2. PMID: 12716242

7. Lee A, Woo J, Ito S. Frequency of infant adverse events that are associated with citalopram use during breast-feeding. Am J Obstet Gynecol. 2004;190:218-21. PMID: 14749663

8. Gentile S., Vozzi F. Consecutive exposure to lamotrigine and citalopram during pregnancy. Arch Womens Ment Health. 2007;10:299-300. PMID: 17763980

9. Werremeyer A. Ziprasidone and citalopram use in pregnancy and lactation in a woman with psychotic depression. Am J Psychiatry. 2009;166:1298. Letter. PMID: 19884241

10. Hale TW, Kendall-Tackett K, Cong Z et al. Discontinuation syndrome in newborns whose mothers took antidepressants while pregnant or breastfeeding. Breastfeed Med. 2010;5:283-8. PMID: 20807106

11. Arya DK, Taylor WS. Lactation associated with fluoxetine treatment. Aust N Z J Psychiatry. 1995;29:697. Letter. PMID: 8825840

12. Egberts ACG, Meyboom RHB, De Koning FHP et al. Non-puerperal lactation associated with antidepressant drug use. Br J Clin Pharmacol. 1997;44:277-81. PMID: 9296322

13. Iancu I, Ratzoni G, Weitzman A et al. More fluoxetine experience. J Am Acad Child Adolesc Psychiatry. 1992;31:755-6. Letter. PMID: 1644743

14. Gonzalez Pablos E, Minguez Martin L, Hernandez Fernandez M et al. [A clinical case of galactorrhoea after citalopram treatment]. Actas Esp Psiquiatr. 2001;29:414. PMID: 11730581

15. Koch HJ, Zellmer H. Marked mydriasis and neuritis nervi optici associated with galactorrhea following citalopram treatment: a case report and discussion. Case Report Med. 2011;2011:191735. PMID: 21869891

16. Belli H, Vardar MK, Yesilyurt S et al. Citalopram related euprolactinaemic galactorrhoea: a case report. West Indian Med J. 2010;59:100-1. PMID: 20931925

17. Trenque T, Herlem E, Auriche P, Drame M. Serotonin reuptake inhibitors and hyperprolactinaemia: a case/non-case study in the French pharmacovigilance database. Drug Saf. 2011;34:1161-6. PMID: 22077504

18. Marshall AM, Nommsen-Rivers LA, Hernandez LL et al. Serotonin transport and metabolism in the mammary gland modulates secretory activation and involution. J Clin Endocrinol Metab. 2010;95:837-46. PMID: 19965920

19. Gorman JR, Kao K, Chambers CD. Breastfeeding among women exposed to antidepressants during pregnancy. J Hum Lact. 2012;28:181-8. PMID: 22344850

Citalopram Identification

Substance Name

Citalopram

CAS Registry Number

59729-33-8

Drug Class

Antidepressants

Serotonin Uptake Inhibitors

Administrative Information

LactMed Record Number

322

Last Revision Date

20130907

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