Paroxetine use while Breastfeeding

Drugs containing Paroxetine: Paxil, Brisdelle, Paxil CR, Pexeva

Paroxetine Levels and Effects while Breastfeeding

Summary of Use during Lactation

Because of the low levels of paroxetine in breastmilk, amounts ingested by the infant are small and paroxetine has not been detected in the serum of most infants tested. Occasional mild side effects have been reported, especially in the infants of mothers who took paroxetine during the third trimester of pregnancy, but the contribution of the drug in breastmilk is not clear. Most authoritative reviewers consider paroxetine one of the preferred antidepressants during breastfeeding.[1][2][3][4] Mothers taking an SSRI during pregnancy and postpartum may have more difficulty breastfeeding and may need additional breastfeeding support.

Drug Levels

Maternal Levels In a pooled analysis of serum levels from published studies and 3 unpublished cases, the authors found 50 mothers taking an average daily dosage of 21 mg (range 10 to 50 mg) had an average milk paroxetine level of 28 mcg/L (range 0 to 153 mcg/L).[2] Using the average dosage and milk level data from this paper, an exclusively breastfed infant would receive an estimated 1.2% of the maternal weight-adjusted dosage of paroxetine.

From data in 6 mothers taking paroxetine in an average daily dosage of 20 mg (range 10 to 30 mg), the authors estimated that an exclusively breastfed infant would receive 1.4% of the maternal weight-adjusted dosage.[1]

At 2 months postpartum, 19 mothers taking an average of 25 mg of paroxetine daily had average milk levels of 13.5 mcg/L at random times after the previous dose. The authors estimated that an exclusively breastfed infant would receive 0.02 mg/kg of paroxetine daily.[5]

A woman had taken paroxetine 15 mg daily during pregnancy. She did not receive a dose in the 22.75 hours before delivery or on the day of delivery. She resumed paroxetine 15 mg daily 24 hours postpartum. At 3.75 hours after the third postpartum dose, her breastmilk paroxetine level was 371 mcg/L.[6]

Four nursing mothers who were 6.5 to 18.5 weeks postpartum were taking paroxetine in doses of 12.5 to 60 mg daily in addition to quetiapine for major depression postpartum. Breastmilk samples obtained at various times after the dose had undetectable (<9.9 mcg/L) levels of paroxetine in 3 mothers. One mother who was taking 50 mg daily had a milk paroxetine level of 255 mcg/L.[7]

Infant Levels Sixteen breastfed infants (2 about 50% breastfed; the others 95% or more breastfed) aged 6 to 13 weeks had undetectable (<1 mcg/L) paroxetine serum levels during maternal therapy with paroxetine in an average daily dosage of 18.75 mg (range 5 to 30 mg).[8]

In a pooled analysis of 40 mother-infant pairs from published and unpublished cases, the authors found that no infants had measurable paroxetine plasma levels.[2]

In 6 breastfed (extent not stated) infants aged 2 to 33 weeks whose mothers were taking paroxetine in an average daily dosage of 20 mg (range 10 to 30 mg), paroxetine was undetectable (<1.6 mcg/L) in all of the infants' serum. One mother taking 20 mg daily and her infant were both poor metabolizers (homozygous for CYP2D6*4), yet no paroxetine was detectable in infant serum.[1]

At 2 months postpartum, the breastfed infants of 19 mothers taking an average of 25 mg of paroxetine daily had an average serum paroxetine level of 0.95 mcg/L which was 5% of the maternal serum level.[5]

Effects in Breastfed Infants

Agitation and difficulty feeding in one infant (age and other details not reported) that were possibly related to paroxetine in breastmilk were reported to the Australian Adverse Drug Reaction Advisory Committee.[9]

In a controlled cohort study of mothers who took paroxetine during pregnancy (diagnoses not reported), 36 mothers took paroxetine during the third trimester and breastfed their infants. Of these, 8 reported side effects in their infants including alertness (6), constipation (3), sleepiness (1), and irritability (1). There were no reports of side effects in the control group of mothers who breastfed and did not use paroxetine in the third trimester or during nursing. The relative contribution of transplacental and breastmilk acquisition of the drug could not be determined.[10]

In a study comparing the infants of mothers who took an SSRI during pregnancy for major depression with the infants of depressed mothers who did not take an SSRI, mental development and most motor development was normal at follow-up averaging 12.9 months in both groups. Four of the treated mothers took paroxetine in doses averaging 28.6 mg daily for an average of 7.8 months while breastfeeding (extent not stated) their infants. Psychomotor development was slightly delayed compared to controls, but the contribution of breastfeeding to abnormal development could not be determined.[11]

A prospective cohort study evaluated 27 infants whose mothers took paroxetine (diagnoses not reported) at an average dose of 20.7 mg daily for at least 2 weeks during breastfeeding (extent not stated). Two control groups consisted of two groups of mothers who neither breastfed nor took an SSRI. All but 7 of the 27 mothers took paroxetine during some part of pregnancy. Weight at 3 months was less in the paroxetine group, but multivariate analysis indicated that maternal paroxetine use was not the determining factor. Weights at 6 and 12 months were not different from the control groups and other developmental milestones were reached at the normal times. One of the paroxetine-exposed infants (age not stated) was reported by the mother to be irritable.[12]

Fifteen mothers who took an average paroxetine dosage of 20.4 mg daily for depression or anxiety starting no later than 4 weeks postpartum, 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 and mothers reported no abnormal effects in their infants.[13]

In 6 breastfed (extent not stated) infants aged 2 to 33 weeks whose mothers were taking paroxetine 10 to 30 mg daily, no adverse reactions were noted clinically at the time of the study.[1]

An infant born to a mother taking paroxetine had serum paroxetine levels about one-third that of the mother's at birth. The infant was a genetic poor metabolizer which apparently was the cause of the high serum levels. Although the infant had symptoms attributed to paroxetine obtained in utero, the mother continued taking paroxetine 30 mg daily and breastfeeding (extent not stated). At 4 months of age, the infant had gained weight normally and had no evidence of neurological side effects.[14]

An 18-month-old infant with a 2-week history of vomiting was found to have hypokalemia, hypochloremic alkalosis and mild dehydration. The infant had been admitted twice previously 2 and 3 months before with a similar picture. Serum renin and aldosterone were normal. The infant's mother had been taking paroxetine 40 mg daily for about 1 year for depression and breastfeeding the infant (extent not stated). Paroxetine was detected, but not quantified, in the mother's breastmilk and infant's serum. Breastfeeding was discontinued and the infant was thriving 6 weeks later with a normal metabolic profile. The authors attributed the infant's metabolic abnormalities to paroxetine-induced syndrome of inappropriate secretion of antidiuretic hormone.[15] The reaction was possibly caused by paroxetine in breastmilk, but strong evidence was lacking and other possible causes cannot be ruled out.

A small study compared the reaction to pain in infants of depressed mothers who had taken an SSRI during pregnancy alone or during pregnancy and nursing, to a control group of unexposed infants of nondepressed mothers. Infants exposed to an SSRI either prenatally alone or prenatally and postnatally via breastmilk had blunted responses to pain compared to control infants. Nineteen of the 30 infants were exposed to paroxetine. Because there was no control group of depressed, nonmedicated mothers, an effect due to maternal behavior caused by depression could not be ruled out. The authors stressed that these findings did not warrant avoiding drug treatment of depression during pregnancy or avoiding breastfeeding during SSRI treatment.[5]

One study of side effects of SSRI antidepressants in nursing mothers found no adverse reactions that required medical attention among 3 infants whose mother was taking paroxetine. No specific information on maternal paroxetine dosage, extent of breastfeeding or infant age was reported.[16]

A nursing mother with bipolar disorder began taking 20 mg of paroxetine at 4 months postpartum and was then started on quetiapine 200 mg twice daily at 6 months postpartum. She breastfed regularly (extent not stated) and no obvious adverse effects were noted in the infant.[17]

Four nursing mothers who were 6.5 to 18.5 weeks postpartum were taking paroxetine in doses of 12.5 to 60 mg daily in addition to quetiapine for major depression postpartum. Their breastfed infants' development were tested at 9 to 18 months of age with the Bayley Scales. Measurements were slightly low on the mental and psychomotor development scale in one infant and on the mental development scale in another; both infants had undetectable (<9.9 mcg/L) serum paroxetine levels. All other infants had scores that were within normal limits. The authors concluded that the low scores of the two infants were probably not caused by the drugs received by the infants in breastmilk.[7]

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.[18]

Possible Effects on Lactation

Paroxetine can cause galactorrhea, usually with increased prolactin levels, in nonpregnant, nonnursing patients.[19][20][21][22][23][24][25] In a study of cases of hyperprolactinemia and its symptoms (e.g., gynecomastia) reported to a French pharmacovigilance center, paroxetine was found to have a 3.1-fold increased risk of causing hyperprolactinemia compared to other drugs.[26] 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 in 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.[27]

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 fluovoxamine, 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.[28]

Alternate Drugs to Consider

Nortriptyline, Sertraline

References

1. 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

2. 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

3. The Academy of Breastfeeding Medicine Protocol Committee. ABM clinical protocol #18: use of antidepressants in nursing mothers. Breastfeed Med. 2008;3:44-52.

4. Lanza di Scalea T, Wisner KL. Antidepressant medication use during breastfeeding. Clin Obstet Gynecol. 2009;52:483-97. PMID: 19661763

5. Oberlander TF, Grunau RE, Fitzgerald C et al. Pain reactivity in 2-month-old infants after prenatal and postnatal serotonin reuptake inhibitor medication exposure. Pediatrics. 2005;115:411-25. PMID: 15687451

6. Knoppert DC, Nimkar R, Principi T, Yuen D. Paroxetine toxicity in a newborn after in utero exposure: clinical symptoms correlate with serum levels. Ther Drug Monit. 2006;28:5-7. PMID: 16418684

7. Misri S, Corral M, Wardrop AA, Kendrick K. Quetiapine augmentation in lactation: a series of case reports. J Clin Psychopharmacol. 2006;26:508-11. PMID: 16974194

8. Hendrick V, Fukuchi A, Altshuler L et al. Use of sertraline, paroxetine and fluvoxamine by nursing women. Br J Psychiatry. 2001;179:163-6. PMID: 11483479

9. Rohan A. Drug distribution in human milk. Aust Prescriber. 1997;20:84.

10. Costei AM, Kozer E, Ho T et al. Perinatal outcome following third trimester exposure to paroxetine. Arch Pediatr Adolesc Med. 2002;156:1129-32. PMID: 12413342

11. Casper RC, Fleisher BE, Lee-Ancajas JC et al. Follow-up of children of depressed mothers exposed or not exposed to antidepressant drugs during pregnancy. J Pediatr. 2003;142:402-8. PMID: 12712058

12. Merlob P, Stahl B, Sulkes J. Paroxetine during breast-feeding: infant weight gain and maternal adherence to counsel. Eur J Pediatr. 2004;163:135-9. PMID: 14745552

13. 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

14. Laine K, Kytola J, Bertilsson L. Severe adverse effects in a newborn with two defective CYP2D6 alleles after exposure to paroxetine during late pregnancy. Ther Drug Monit. 2004;26:685-7. PMID: 15570195

15. Abdul Aziz A, Agab WA, Kalis NN. Severe paroxetine induced hyponatremia in a breast fed infant. J Bahrain Med Soc. 2004;16:195-8.

16. 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

17. Ritz S. Quetiapine monotherapy in post-partum onset bipolar disorder with a mixed affective state. Eur Neuropsychopharmacol. 2005;15 (Suppl 3):S407. Abstract.

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

19. Davenport E, Velamoor R. A case of paroxetine-induced galactorrhea. Can J Psychiatry. 2002;47:890-1. PMID: 12500767

20. Morrison J, Remick RA, Leung M et al. Galactorrhea induced by paroxetine. Can J Psychiatry. 2001;46:88-9. PMID: 11221498

21. Bonin B, Vandel P, Sechter D et al. Paroxetine and galactorrhea. Pharmacopsychiatry. 1997;30:133-4. PMID: 9271780

22. Gonzalez E , Minguez L, Sanguino RM. Galactorrhea after paroxetine treatment. Pharmacopsychiatry. 2000;33:118. Letter. PMID: 10855465

23. 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

24. Chakraborty S, Sanyal D, Bhattacharyya R, Dutta S. A case of paroxetine-induced galactorrhoea with normal serum prolactin level. Indian J Pharmacol. 2010;42:322-3. http://www.ijp-online.com/text.asp?2010/42/5/322/70399

25. Sertcelik S, Bakim B, Karamustafalioglu O. [High dose paroxetine-induced galactorrhea with normal serum prolactin level: A case report]. Klin Psikofarmakol Bul. 2012;22:355-6.

26. 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

27. 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

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

Paroxetine Identification

Substance Name

Paroxetine

CAS Registry Number

61869-08-7

Drug Class

Administrative Information

LactMed Record Number

327

Information from the National Library of Medicine's LactMed Database.

Last Revision Date

2013-09-07

Disclaimer

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