May 27 2022




Recommendations

Some studies indicate that citalopram, including major active metabolite desmethylcitalopram, can reach a concentration in milk two or three times superior to that of plasma [1][2], although its concentration in the serum of the infant may be undetectable or very low. In a study on 10 patients, in four infants no drug was detected in the serum, whereas in the remaining babies citalopram reached a low level [1][3]. Based on studies of small numbers of cases, the data indicate that citalopram produced higher levels of the drug in 17% of infants[4]. Several studies indicate that the exclusively breastfed infant whose mother is treated with citalopram, receives between 5-8% of the maternal dose weight-adjusted [1][2].

The amount of medicine received by the baby and the final serum concentration is rather related to the characteristics of metabolism of child and mother than with the administered dose.That illustrates one case report about a mother, poor metabolizer of the CYP2C19 isoenzyme, whose son recorded low levels of citalopram during breastfeeding, but not presented any symptoms [3].

Clinical manifestations

The U.S. manufacturer sheet of citalopram (http://www.celexa.com/pdf/celexa_pi.pdf) reports two cases of infants experiencing excessive somnolence, decreased appetite and weight loss in relation with the administration of citalopram to his mother. In one case recovery was complete after withdrawal of the drug. According to the data sheet, there is no follow-up data of the second case.

Another case study does not reflect any effect of citalopram [2]. Systematic monitoring for six months to three infants whose mothers received 15 mg of citalopram did not reveal any influence on weight development of infants who were exclusively breastfed for four months and partially the remaining two months.[5].

An essay on a group of 31 mother-child pairs exposed to citalopram (10-60 mg / day) compared with two other groups of 31 and 12 pairs as controls showed no significant difference in the incidence of adverse reactions between the three groups. There was one case of agitation and irritability in an infant when initiating therapy with citalopram, two months after delivery, which yielded to discontinue antidepressant treatment by the mother[6].

An infant of 5 months of age showed restlessness during sleep that disappeared with the reduction of the maternal dose of citalopram (40 mg/day) and replacing two breast feeds by bottle. The case was attributed to treatment with citalopram. The drug concentration in the milk was 205 ng/ml, whereas in maternal serum showed 98.9 ng/ml. In the infant the level of citalopram was 12.7 ng/ml in serum [7].

When considering the possible adverse effects of citalopram, should also be considered prenatal exposure to the drug. Infants exposed to selective inhibitors of serotonin reuptake during late pregnancy are at increased risk of central serotonergic effects, the severity of which runs parallel with the concentration of 5-hydroxyindoleacetic acid in umbilical cord bloodl[8]. A case report of irregular breathing, sleep disturbance, besides hipotyon?a and hypertonia in an infant two weeks old whose mother received citalopram, is interpreted by the authors of the communication as a case of withdrawal syndrome of the drug, rather than an adverse effect of this[9].

As with other antidepressants, infants exposed for two or more months to maternal depression, experience less weight gain than children of euthymic mothers or with a shorter depression[5].

Influence on development

There is no evidence regarding influence of exposure to citalopram through breast milk in infants followed until the age of one year. Monitoring of nine infants exposed to citalopram from before birth (6 with exclusive breast feeding, 3 with complementary) until they were one year-old, showed normal development, both in weight as psychomotor[1].

The available literature is about 11 studies, including 306 children that seem to support the absence of impaired psychomotor development following exposure to SSRIs both prenatal and postnatal[10].

Influence on lactation

Selective inhibitors of serotonin reuptake, including citalopram, can cause elevated blood prolactin levels and subsequently galactorrhea[11]. Although it is not know the clinical significance of this fact on breastfeeding, probably have no negative influences on it.

Recommendations

Despite the few case reports of adverse effects in infants, the limitations of the available studies and the minimum sample sizes, make uncertain formulate some kind of recommendation on antidepressants inhibitors of serotonin reuptake in nursing mothers. The data available does not allow the opportunity to advise about changing one of these drugs by another when the patient is clinically stable. Ideally, the better way is to assess individually each patient, trying to get a proper emotional response of the mother with minimal risks to the baby[4].

If there are reasons for prescribing citalopram to the mother, there are no arguments to stop breastfeeding, although the baby must be monitored closely, mainly the occurrence of behavioral disturbances. In these cases, escitalopram, administered at doses significantly lower but with equivalent effects, provides minor expositions of this drug to the baby, especially if it's a preterm infant or with low birth weight[3].

Minimize the maternal dose of citalopram may be a reasonable approach[4], and also to use the lowest dose that result effective to control the patient and reduce feedings during the phase of maximum concentration of the drug in the milk [7]. The peak concentration of citalopram in breast milk is reached between three and nine hours after taking the drug, which is an argument for administering it preferably before or with the meal that precedes the larger interval between meals[2].

These claims briefly sumarize the state of scientific evidence on this subject: "All studies reviewed have procedural defects and screening instruments used have limitations, particularly in assessing the effects on infants. It is not advisable to extend the generalization that emerges from few tests to all cases. Thus, the findings of these few studies and communications are inconclusive and can not clarify the repercussions of antidepressant treatment with SSRIs on the long-term neurocognitive development of children "[10].

References

1. Heikkinen T, Ekblad U, Kero P, Ekblad S, Laine K. Citalopram in pregnancy and lactation. Clin Pharmacol Ther. 2002 Aug; 72(2): 184-91.
2. Jensen PN, Olesen OV, Bertelsen A, Linnet K. Citalopram and desmethylcitalopram concentrations in breast milk and in serum of mother and infant. Ther Drug Monit. 1997 Apr;19(2):236-9.
3. Berle JO, Steen VM, Aamo TO, Breilid H, Zahlsen K, Spigset O. Breastfeeding during maternal antidepressant treatment with serotonin reuptake inhibitors: infant exposure, clinical symptoms, and cytochrome p450 genotypes J Clin Psychiatry. 2004 Sep; 65(9): 1228-34.
4. Weissman AM, Levy BT, Hartz AJ, Bentler S, Donohue M, Ellingrod VL, Wisner KL. Pooled analysis of antidepressant levels in lactating mothers, breast milk, and nursing infants. Am J Psychiatry. 2004 Jun;161(6):1066-78.
5. Hendrick V, Smith LM, Hwang S, Altshuler LL, Haynes D. Weight gain in breastfed infants of mothers taking antidepressant medications.J Clin Psychiatry. 2003 Apr;64(4):410-2.
6. 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 Jan;190(1):218-21.
7. Schmidt K, Olesen OV, Jensen PN. Citalopram and breast-feeding: serum concentration and side effects in the infant.Biol Psychiatry. 2000 Jan 15; 47(2):164-5.
8. Laine K, Heikkinen T, Ekblad U, Kero P. Effects of exposure to selective serotonin reuptake inhibitors during pregnancy on serotonergic symptoms in newborns and cord blood monoamine and prolactin concentrations. Arch Gen Psychiatry. 2003 Jul;60(7):720-6.
9. Franssen EJ, Meijs V, Ettaher F, Valerio PG, Keessen M, Lameijer W. Citalopram serum and milk levels in mother and infant during lactation.Ther Drug Monit. 2006 Feb;28(1):2-4.
10. Gentile S. SSRIs in pregnancy and lactation: emphasis on neurodevelopmental outcome.CNS Drugs. 2005;19(7):623-33.
11. Gonzalez Pablos E, Minguez Martin L, Hernandez Fernandez M, Sanguina Andres RM. A clinical case of galactorrhoea after citalopram treatment. Actas Esp Psiquiatr. 2001 Nov-Dec;29(6):414.
12. Llewellyn A, Stowe ZN. Psychotropic medications in lactation J Clin Psychiatry. 1998;59 Suppl 2:41-52.

Warning of the manufacturer:

The shortage of available clinical observations requires caution in pregnant women and during lactation. Preclinical studies have shown that very low concentrations of citalopram pass into milk.

Updated:05.04.08