Antidepressant
PREGNANCY RECOMMENDATION: Human Data Suggest Risk in 3rd Trimester
BREASTFEEDING RECOMMENDATION: Limited Human Data—Potential Toxicity
PREGNANCY SUMMARY
Citalopram does not appear to be a major human teratogen. Only one of the studies below observed an increase in defects or pattern of major anomalies over that expected in a nonexposed population. (See Paroxetine.) However, selective serotonin reuptake inhibitor (SSRI) antidepressants, including citalopram, have been associated with several developmental toxicities, including spontaneous abortions (SABs), low birth weight, prematurity, neonatal serotonin syndrome, neonatal behavioral syndrome (withdrawal), possibly sustained abnormal neurobehavior beyond the neonatal period, respiratory distress, and persistent pulmonary hypertension of the newborn (PPHN).
FETAL RISK SUMMARY
The antidepressant, citalopram, is an SSRI that has a chemical structure unrelated to those of other antidepressants (1). All the antidepressant agents in this class (citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline) share a similar mechanism of action, although they have different chemical structures. These differences could be construed as evidence against any conclusion that they share similar effects on the embryo, fetus, or newborn. In the mouse embryo, however, craniofacial morphogenesis appears to be regulated, at least in part, by serotonin. Interference with serotonin regulation by chemically different inhibitors produces similar craniofacial defects (2). Regardless of the structural differences, therefore, some of the potential adverse effects on the pregnancy may also be similar.
Both mating and fertility were reduced in male and female rats at oral doses approximately five times the maximum recommended human daily dose of 60 mg/day based on BSA (MRHD). The duration of gestation was increased at approximately eight times the MRHD. Citalopram demonstrated dose-related embryo and fetal growth restriction, reduced survival, and teratogenicity in rats dosed during organogenesis at about 18 times the MRHD (1). Fetal malformations included cardiovascular and skeletal defects, but the dose was maternal toxic (clinical signs, decreased weight gain). The developmental no-effect dose was about nine times the MRHD. In contrast, no developmental adverse effects were observed in the offspring of pregnant rabbits given doses up to about five times the MRHD (1).
Increased offspring mortality during the first 4 days after birth and persistent growth restriction were observed when pregnant rats were dosed at about five times the MRHD throughout gestation and early lactation. Similar effects were observed with doses about four times the MRHD in late gestation through weaning. The no-effect dose in this group was about twice the MRHD (1).
In an in vitro experiment using a single placental cotyledon, both citalopram and its metabolite desmethylcitalopram crossed to the fetal side (3). The mean steady-state placental transfer for the two compounds was 9.1% and 5.6%, respectively. A 2003 study of the placental transfer of antidepressants found cord blood:maternal serum ratios for citalopram and its metabolite that were 0.17–1.42 and 0.50–1.00, respectively (4). The dose-to-delivery interval was 14–48 hours, with the highest ratio for the parent drug and metabolite occurring at 48 hours.
In a 2002 study, 11 women took citalopram (20–40 mg/day) during pregnancy; 10 throughout gestation and 1 starting at 20 weeks’ gestation (5). The mean ratio of two metabolites was significantly higher during pregnancy than at 2 months postdelivery, indicating induction of the CYP2D6 isoenzyme (5). The trough plasma concentrations of citalopram, desmethylcitalopram, and didesmethylcitalopram in the normal newborns were 64%, 66%, and 68% of the maternal concentrations, respectively. The neurodevelopment of the infants up to the age of 1 year was normal (5). All infants were breastfed (see Breastfeeding Summary).
Citalopram is at least eight times more potent in the inhibition of serotonin reuptake than its four metabolites (1). It has an elimination half-life of approximately 35 hours. This is in the same general range as the other SSRI agents with weakly active or inactive metabolites (elimination half-lives of parent compounds in parentheses): fluvoxamine (15.6 hours), paroxetine (21 hours), and sertraline (26 hours). All have much shorter elimination half-lives than fluoxetine (4–6 days) or fluoxetine’s active metabolite (4–16 days).
A brief 1993 case report described a woman who was treated with citalopram for major depression during the first 6 weeks of an undiagnosed pregnancy (6). She received 40 mg/day during the first 3 weeks, and then the dose was increased to 60 mg/day. She also took several other drugs for coexisting panic disorder and migraine headaches. All medication was stopped in the sixth week of gestation when the pregnancy was diagnosed. Because of her deteriorating mental status and anxiety concerning fetal development, she requested an abortion, which was performed at 12 weeks’ gestation. At autopsy, a thorough macroscopic and microscopic evaluation, including a detailed neuropathological examination, found no evidence of malformation (6).
Five male infants exposed to citalopram (30 mg/day), paroxetine (10–40 mg/day), or fluoxetine (20 mg/day) during gestation exhibited withdrawal symptoms at or within a few days of birth and lasting up to 1 month (7). Symptoms included irritability, constant crying, shivering, increased tonus, eating and sleeping problems, and convulsions.
A 2004 prospective study examined the effect of four SSRIs (citalopram, fluoxetine, paroxetine, and sertraline) on newborn neurobehavior, including behavioral state, sleep organization, motor activity, heart rate variability, tremulousness, and startles (8). Seventeen SSRI-exposed, healthy, full-birth-weight newborns and 17 nonexposed, matched controls were studied. A wide range of disrupted neurobehavioral outcomes were shown in the subject infants. After adjustment for gestational age, the exposed infants were found to differ significantly from controls in terms of tremulousness, behavioral states, and sleep organization. The effects observed on motor activity, startles, and heart rate variability were not significant after adjustment (8).
A 2003 prospective study evaluated the pregnancy outcomes of 138 women treated with SSRIantidepressants during gestation (9). Women using each agent were 73 fluoxetine, 36 sertraline, 19 paroxetine, 7 citalopram, and 3 fluvoxamine. Most (62%) took an SSRI throughout pregnancy and 95% were taking an SSRI at delivery. Birth complications were observed in 28 infants, including preterm birth (9 cases), meconium aspiration, nuchal cord, floppy at birth, and low birth weight. Four infants (2.9%) had low birth weight, all exposed to fluoxetine (40–80 mg/day) throughout pregnancy, including two of the three infants of mothers taking 80 mg/day. One infant had Hirschsprung disease, a major defect, and another had cavum septi pellucidi (neither the size of the cavum nor the SSRI agents were specified) (9). The clinical significance of the cavum septi pellucidi is doubtful as it is nearly always present at birth but resolves in the first several months (10).
The database of the World Health Organization (WHO) was used in a 2005 report on neonatal SSRI withdrawal syndrome (11). In this database, 93 suspected cases with either neonatal convulsions or withdrawal syndrome were identified in the WHO database. The agents were 63 paroxetine, 13 fluoxetine, 1 paroxetine plus fluoxetine, 9 sertraline, and 7 citalopram. The analysis suggested that paroxetine might have an increased risk of convulsions or withdrawal compared with other SSRIs (11).
Evidence for the neonatal behavioral syndrome that is associated with in utero exposure to SSRIs and serotonin and norepinephrine reuptake inhibitors (SNRIs) (collectively called serotonin reuptake inhibitors [SRIs]) in late pregnancy was reviewed in a 2005 reference (12). The report followed a recent agreement by the FDA and manufacturers for a class labeling change about the neonatal syndrome. Analysis of case reports, case series, and cohort studies revealed that late exposure to SRIs carried an overall risk ratio of 3.0 (95% confidence interval [CI] 2.0–4.4) for the syndrome compared with early exposure. The case reports (N = 18) and case series (N = 131) involved 97 cases of paroxetine, 18 fluoxetine, 16 sertraline, 12 citalopram, 4 venlafaxine, and 2 fluvoxamine. There were nine cohort studies analyzed. The typical neonatal syndrome consisted of central nervous system, motor, respiratory, and gastrointestinal signs that were mild and usually resolved within 2 weeks. Only one of 313 quantifiable cases involved a severe syndrome consisting of seizures, dehydration, excessive weight loss, hyperpyrexia, and intubation. There were no neonatal deaths attributable to the syndrome (12).
A significant increase in the risk of low birth weight (<10th percentile) and respiratory distress after prenatal exposure to SSRIs was reported in 2006 (13). The population-based study, representing all live births (N = 119,547) during a 39-month period in British Columbia, Canada, compared pregnancy outcomes of depressed mothers treated with SSRIs with outcomes in depressed mothers not treated with medication and in nonexposed controls. The severity of depression in the depressed groups was accounted for by propensity score matching (13).
A 30% incidence of SSRI-induced neonatal abstinence syndrome was found in a 2006 cohort study (14). Sixty neonates with prolonged in utero exposure to SSRIs were compared to nonexposed controls. The agents used were paroxetine (62%), fluoxetine (20%), citalopram (13%), venlafaxine (3%), and sertraline (2%). Assessment was conducted by the Finnegan score. Ten of the infants had mild and eight had severe symptoms of the syndrome. The maximum mean score in infants with severe symptoms occurred within 2 days of birth, but some occurred as long as 4 days after birth. Because of the small numbers, a dose–response could only be conducted with paroxetine. Infants exposed to mean maternal doses that were <19 mg/day had no symptoms, <23 mg/day had mild symptoms, and 27 mg/day had severe symptoms (14).
A 2005 prospective comparative study of citalopram in pregnancy was reported in 2005 (15). Three groups, citalopram, disease, and nonteratogen, each containing 132 pregnant women were closely matched. In the citalopram group, 125 (95%) took the drug at least in the 1st trimester and 71 (54%) continued the drug throughout gestation. The outcomes in the citalopram-exposed pregnancies were 114 live births, 14 SABs, 2 elective abortions, and 2 stillbirths. One male infant, exposed during organogenesis, had a major anomaly (umbilical and scrotal hernia). There were no statistical differences among the three groups in terms of mean birth weight, structural defects, gestational age at birth, and fetal survival. However, for infants exposed in the 3rd trimester, there were increased risks for complications in general (relative risk [RR] 1.5, 95% CI 1.0–2.4) and for neonatal intensive care unit (NICU) admissions (RR 4.2, 95% CI 1.7–10.3) (i.e., poor neonatal adaptation syndrome) (15).
A meta-analysis of clinical trials (1990–2005) with SSRIs was reported in 2006 (16). The SSRI agents included were citalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline. The specific outcomes analyzed were major, minor, and cardiac malformations, and SABs. The odd ratio [OR] with 95% CI for the four outcomes were 1.394 (0.906–2.145), 0.97 (0.13–6.93), 1.193 (0.531–2.677), and 1.70 (1.28–2.25), respectively. Only the risk of SABs was significantly increased (16).
A brief 2005 report described significant associations between the use of SSRIs in the 1st trimester and congenital defects (17). The data were collected by the CDC-sponsored National Birth Defects Prevention Study in an on-going case–control study of birth defect risk factors. Case infants (N = 5357) with major birth defects were compared with 3366 normal controls. A positive association was found with omphalocele (N = 161; OR 3.0, 95% CI 1.4–6.1). Paroxetine, which accounted for 36% of all SSRI exposures, had the strongest association with the defect (OR 6.3, 95% CI 2.0–19.6). The study also found a significant association between the use of any SSRI and craniosynostosis (N = 372; OR 1.8, 95% CI 1.0–3.2) (17). An expanded report from this group was published in 2007 (see reference 25 below).
In 1999, the Swedish Medical Birth Registry compared the use of antidepressants in early pregnancy and delivery outcome for the years 1995–1997 (18). There were no significant differences for birth defects, infant survival, or risk of low birth weight (<2500 g) among singletons between those exposed to any depressant, SSRIs only, and non-SSRIs only, but a shorter gestational duration (<37 weeks) was observed for any antidepressant exposure (OR 1.43, 95% CI 1.14–1.80). Fifteen (4.0%) of the citalopram-exposed infants had anomalies, but one was a trisomy 13 syndrome and five were classified as uncertain anomalies (18). A second Registry report, published in 2006 covering the years 1995–2003, analyzed the relationship between antidepressants and major malformations and cardiac defects (19). There was no significant increase in the risk of major malformations with any antidepressant. The strongest effect among cardiac anomalies was with ventricular or atrial septum defects (VSDs-ASDs). Significant increases were found with paroxetine (OR 2.22, 95% CI 1.39–3.55) and clomipramine (OR 1.87, 95% CI 1.16–2.99 (19). In 2007, the analysis was expanded to include the years 1995–2004 (20). There were 6481 women (6555 infants) who had reported the use of SSRIs in early pregnancy. The number of women using a single SSRI during the 1st trimester was 2579 citalopram, 1807 sertraline, 908 paroxetine, 860 fluoxetine, 66 escitalopram, and 36 fluvoxamine. After adjustment, only paroxetine was significantly associated with an increased risk of cardiac defects (N = 13, RR 2.62, 95% CI 1.40–4.50) or VSDs-ASDs (N = 8, RR 3.07, 95% CI 1.32–6.04). Analysis of the combined SSRI group, excluding paroxetine, revealed no associations with cardiac defects or VSDs-ASDs. The study also found no association with omphalocele or craniostenosis (20).
A 2007 study evaluated the association between 1st-trimester exposure to paroxetine and cardiac defects by quantifying the dose–response relationship (21). A population-based pregnancy registry was used by linking three administrative databases so that it included all pregnancies in Quebec between 1997 and 2003. There were 101 infants with major congenital defects, 24 involving the heart, among the 1403 women using only one type of antidepressant during the 1st trimester. The use of paroxetine or other SSRIs did not significantly increase the risk of major defects or cardiac defects compared with non-SSRI antidepressants. However, a paroxetine dose >25 mg/day during the 1st trimester was significantly associated with an increased risk of major defects (OR 2.23, 95% CI 1.19–4.17) and of cardiac defects (OR 3.07, 95% CI 1.00–9.42) (21).
A 2007 retrospective cohort study examined the effects of exposure to SSRIs or venlafaxine in the 3rd trimester on 21 premature and 55 term newborns (22). The randomly selected unexposed control group consisted of 90 neonates of mothers not taking antidepressants, psychotropic agents, or benzodiazepines at the time of delivery. There were significantly more premature infants among the subjects (27.6%) than in controls (8.9%), but the groups were not matched. The antidepressants, number of subjects, and daily doses in the exposed group were paroxetine (46; 5––40 mg), fluoxetine (10; 10–40 mg), venlafaxine (9; 74–150 mg), citalopram (6; 10–30 mg), sertraline (3; 125–150 mg), and fluvoxamine (2; 50–150 mg). The behavioral signs that were significantly increased in exposed compared with nonexposed infants were central nervous system (CNS) —abnormal movements, shaking, spasms, agitation, hypotonia, hypertonia, irritability, and insomnia; respiratory system—indrawing, apnea/bradycardia, and tachypnea; and other—vomiting, tachycardia, and jaundice. In exposed infants, CNS (63.2%) and respiratory system (40.8%) signs were most common, appearing during the first day of life and lasting for a median duration of 3 days. All of the exposed premature infants exhibited behavioral signs compared with 69.1% of exposed term infants. The duration of hospitalization was significantly longer in exposed premature compared with nonexposed premature infants, 14.5 days vs. 3.7 days, respectively. In 75% of the term and premature infants, the signs resolved within 3 and 5 days, respectively. There were six infants in each group with congenital malformations, but the drugs involved were not specified (22).
A 2007 review conducted a literature search to determine the risk of major congenital malformations after 1st trimester exposure to SSRIs and SNRIs (23). Fifteen controlled studies were analyzed. The data were adequate to suggest that citalopram, fluoxetine, sertraline, and venlafaxine were not associated with an increased risk of congenital defects. In contrast, the analysis did suggest an increased risk with paroxetine. The data were inadequate to determine the risk for the other SSRIs and SNRIs (23).
A case–control study, published in 2006, was conducted to test the hypothesis that exposure to SSRIs in late pregnancy was associated with persistent pulmonary hypertension of the newborn (24). A total of 1213 women were enrolled in the study, 377 cases whose infants had PPHN and 836 matched controls and their infants. Mothers were interviewed by nurses who were blinded to the hypothesis. Fourteen case infants had been exposed to an SSRI after the 20th week of gestation compared with six control infants (adjusted odds ratio 6.1, 95% CI 2.2–16.8). The numbers were too small to analyze the effects of dosage, SSRI used, or reduction of the length of exposure before delivery. No increased risk of PPHN was found with the use of SSRIs before the 20th week or with the use of non-SSRI antidepressants at any time in pregnancy. If the relationship was causal, the absolute risk was estimated to be about 1% (24).
Two large case–control studies assessing associations between SSRIs and major birth defects were published in 2007 (25,26). The findings related to SSRIs as a group, as well as to four specific agents: citalopram, fluoxetine, paroxetine, and sertraline. One of the studies did find a significant association between citalopram and a group of defects (anencephaly, craniosynostosis, and omphalocele) (25). An accompanying editorial discussed the findings and limitations of these and other related studies (27). Details of the studies and the editorial are described in the paroxetine review (see Paroxetine).
A prospective cohort study evaluated a large group of pregnancies exposed to antidepressants in the 1st trimester to determine if there was an association with major malformations (28). The patient population came from the Motherisk database and involved 928 cases that met their criteria. The 928 matched (for age, smoking, and alcohol use) controls were pregnancies not exposed to antidepressants or known teratogens. In addition to the 184 citalopram cases, the other cases were 113 bupropion, 21 escitalopram, 61 fluoxetine, 52 fluvoxamine, 68 mirtazapine, 39 nefazodone, 148 paroxetine, 61 sertraline, 17 trazodone, and 154 venlafaxine. In the antidepressant group, there were 24 (2.5%) major defects compared with 25 (2.6%) in controls (odds ratio 0.9, 95% CI 0.5–1.61). There were eight major anomalies in the citalopram group: umbilical hernia, duplex kidney, club foot, pyloric stenosis, neural tube defect, atrial septal defect, congenital pneumothorax, and hypospadias. There were no major defects in the pregnancies exposed to bupropion, escitalopram, or trazodone (28).
BREASTFEEDING SUMMARY
Citalopram is excreted into human milk. A 1997 report described breast milk concentrations of the antidepressant in two lactating women under treatment for depression and one healthy lactating volunteer (29). All three subjects were extensive metabolizers of citalopram with respect to the liver enzymes (CYP2C19 and CYP2D6) involved in the metabolism of the drug. The two women with depression were being treated with 20 mg/day and 40 mg/day at 2 and 4 months postpartum, respectively. The healthy volunteer was given a single dose of 40 mg at 10 months postpartum. The milk:serum ratio in the two women ranged from 1.16 to 1.88, whereas in the volunteer, the ratio was 1.00, based on the AUC. The dose ingested by an infant was calculated to range from 4.3 to 17.6 mcg/kg/day (0.7%–5.9% of the weight-adjusted maternal dose) in the two women on chronic therapy, and 11.2 mcg/kg/day (1.8% of the weight-adjusted maternal dose based on AUC) in the volunteer. The two mothers on chronic therapy observed no adverse effects in their nursing infants. Compared with other SSRI antidepressants, the relative dose to the infant from citalopram (0.7%–5.9%) was comparable to fluoxetine and its active metabolite (1.2%–6.5%) but higher than that for fluvoxamine (0.5%), sertraline (0.45%), and paroxetine (0.34%). Based on these data, the authors recommended that caution should be used with the administration of citalopram during lactation (29).
In a second 1997 report, a 21-year-old mother developed severe depression 2 months after delivery of a female infant and was begun on citalopram (30). Blood and milk samples were collected after 8 days of a continuous 20 mg/day dose. The mean milk:serum ratio over a 24-hour period was approximately 3 for both citalopram and its inactive metabolite. The estimated citalopram weight-adjusted infant dose was 4.8% of the mother’s dose. After 3 weeks of therapy, the citalopram serum concentration in the infant was about 1/15th of the mother’s trough level; the metabolite was undetectable. The levels indicated that no accumulation of citalopram or the metabolite occurred in the infant. No adverse effects or unusual behavior were observed in the infant (30).
A 2000 report measured citalopram concentrations in the milk and plasma of seven women who were nursing their infants (mean age 4.1 months) (31). The median citalopram dose was 0.36 mg/kg/day. The mean milk:plasma ratios of citalopram and the metabolite, desmethylcitalopram, were 1.8 (range 1.2–3) and 1.8 (range 1.0–2.5), respectively. Citalopram was detected in the plasma of three infants (2.0–2.3 ng/mL), two of which also had detectable levels of the metabolite (2.2 ng/mL). The mean combined dose of citalopram and metabolite (expressed as a percentage of the maternal weight-normalized dose) was 4.4%–5.1%. No adverse effects were observed in the infants and all had normal Denver developmental quotients (31).
A 29-year-old woman, 4 weeks after delivery, was started on citalopram (40 mg/day) for postpartum depression (32). Eight days later, single samples of milk and maternal serum (time from last dose not specified) yielded concentrations of 205 ng/mL and 98.9 ng/mL, respectively. Uneasy sleep was noted in the breastfed infant starting about 2–3 days after initiation of drug therapy. The citalopram concentration in the infant’s serum after 16 days of maternal therapy was 12.7 ng/mL. Reducing the dose to 20 mg/day and substituting two breastfeedings with artificial nutrition normalized the infant’s sleeping. One week later, the serum concentrations of citalopram in the mother and infant were 49.0 ng/mL and 4.5 ng/mL, respectively (32).
In their product information, the manufacturer describes two infants with excessive somnolence, decreased feeding, and weight loss associated with nursing from mothers receiving citalopram (1). Both cases involved reports to the manufacturer that apparently were not published. Although the information is incomplete, the manufacturer was able to obtain partial details of these cases (G. Fagen, personal communication, Forrest Pharmaceuticals, 2000). One full-term infant was born to a Danish woman who had been started on citalopram, 40 mg/day, shortly before delivery. The infant was presumably breastfed. When the adverse effects were noted 3–4 days after birth, the mother stopped the drug. The infant made a full recovery. The second case involved an 8-day-old Swedish baby who developed tiredness, weight loss, and decreased suckling. The mother had started taking citalopram, 20 mg/day, approximately 1 year earlier. She was also taking an antihistamine. Five days before the onset of the adverse symptoms, without medical advice, she increased her dose to 30 mg/day. A single milk sample (timing in relationship to the dose not specified) yielded a drug concentration of 377 nmol/L (about 0.122 mcg/mL) (1 mol of citalopram = 324.4 g (23)). The concentration of the metabolite was 111 nmol/L. These amounts are very close to those reported in the above published cases. No other details of the case were available, although it is known that the infant was doing well at 4 years of age.
Nine women treated with citalopram during pregnancy (see Fetal Risk Summary) continued to use the antidepressant while nursing their infants (5). Maternal plasma concentrations of the parent compound and metabolites demonstrated a tendency to rise at 2 weeks and 2 months postpartum. The milk:plasma ratios for citalopram, desmethylcitalopram, and didesmethylcitalopram ranged from 1.2 to 3.3, 1.3 to 4.1, and 1.1 to 4.6, respectively. In contrast, the infant plasma concentrations of the parent compound and two metabolites at various intervals up to 2 months of age all declined from those measured at birth. The weight and neurodevelopment of the infants up to 1 year of age were normal (5).
A prospective, observational cohort study designed to determine the frequency of adverse effects in nursing infants exposed to citalopram in milk was published in 2004 (33). Three groups of nursing women were formed: 31 women who were depressed and taking citalopram; 12 women who were depressed but who were taking other SSRI antidepressants; and 31 healthy women matched to the first group by maternal age and parity. There was no statistically significant difference in the rate of adverse events among the nursing infants in the three groups (3/31 events, 0/12 events, and 1/31 events, respectively). In the citalopram group, two of the events were colic and decreased feeding, but both were considered nonspecific and insignificant and did not require intervention. The third event involved irritability and restlessness that were observed in the infant when the mother started citalopram at 2 months postpartum. Breastfeeding was stopped after 2 weeks and the symptoms resolved (33).
A 2004 study was conducted in 25 women (nursing 26 infants) to quantify the concentration of the SSRI or SNRI in their breast milk (34). The antidepressants taken by the women were citalopram (nine mothers/10 infants), paroxetine (six), sertraline (six), fluoxetine (one), and venlafaxine (three). The maternal mean dose of citalopram was 24 mg/day (20–50 mg/day). The mean milk concentration was 389 nmol/L (157–725 nmol/L, resulting in a theoretical maximum infant dose that was 5.2% of the mother’s weight-adjusted dose. Citalopram was detected in six of the infants serum (mean 1.9 nmol/L, range 0–8 nmol/L). There was no evidence of adverse effects in the breastfeeding infants (34).
A 2010 study using human and animal models found that drugs that disturb serotonin balance such as SSRIs and SNRIs can impair lactation (35). The authors concluded that mothers taking these drugs may need additional support to achieve breastfeeding goals.
A 1999 review of SSRI agents concluded that if there were compelling reasons to treat a mother for postpartum depression, a condition in which a rapid antidepressant effect is important, the benefits of therapy with SSRIs would most likely outweigh the risks (36). Nevertheless, nursing women receiving citalopram, in particular those taking doses >20 mg/day or concurrently with other sedative agents, should be warned of the potential for toxicity in their infants. Moreover, the long-term consequences of exposure to SSRI antidepressants in breast milk on the infant’s neurobehavior development are unknown (no such adverse effects have been reported to date, but additional research is needed). Avoiding nursing around the time of peak maternal concentrations (about 4 hours after a dose) may limit infant exposure. However, the long elimination half-lives of all SSRIs and their weakly basic properties, which are conducive to ion trapping in the relatively acidic milk, probably will lessen the effectiveness of this strategy. The American Academy of Pediatrics classifies other SSRIs as drugs whose effect on the nursing infant is unknown but may be of concern (see Fluoxetine, Fluvoxamine, Paroxetine, and Sertraline).
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