The Basics

What is Fluoxetine?

An SSRI often used to treat depression, and also sometimes obsessive compulsive disorder and bulimia.

Brand names for Fluoxetine

Prozac

How Fluoxetine is classified

Antidepressive Agents, Serotonin Uptake Inhibitors

Fluoxetine During Pregnancy

Fluoxetine pregnancy category

Category N/ANote that the FDA has deprecated the use of pregnancy categories, so for some medications, this information isn’t available. We still think it’s useful to list historical info, however, given what a common proxy this has been in the past.

What we know about taking Fluoxetine while pregnant

Can you take fluoxetine while pregnant? Taking fluoxetine during pregnancy, exclusively in the first trimester, is unlikely to increase the chance for birth defects. Fluoxetine is one of the better-studied antidepressants in pregnancy. There are reports on over 10,000 (ten thousand) pregnancies exposed to fluoxetine during the first trimester.

Taking Fluoxetine While Breastfeeding

What are recommendations for lactation if you're taking Fluoxetine?

The average amount of drug in breastmilk is higher with fluoxetine than with most other SSRIs and the long-acting, active metabolite, norfluoxetine, is detectable in the serum of most breastfed infants during the first 2 months postpartum and in a few thereafter. Adverse effects such as colic, fussiness, and drowsiness have been reported in some breastfed infants. Decreased infant weight gain was found in one study, but not in others. No adverse effects on development have been found in a few infants followed for up to a year. If fluoxetine is required by the mother, it is not a reason to discontinue breastfeeding. If the mother was taking fluoxetine 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 breastfed infant should be monitored for behavioral side effects such as colic, fussiness or sedation and for adequate weight gain. Mothers taking an SSRI during pregnancy and postpartum may have more difficulty breastfeeding, although this might be a reflection of their disease state.[1] These mothers may need additional breastfeeding support. Breastfed infants exposed to an SSRI during the third trimester of pregnancy have a lower risk of poor neonatal adaptation than formula-fed infants.

Maternal / infant drug levels

The average amount of drug in breastmilk is higher with fluoxetine than with most other SSRIs and the long-acting, active metabolite, norfluoxetine, is detectable in the serum of most breastfed infants during the first 2 months postpartum and in a few thereafter. Adverse effects such as colic, fussiness, and drowsiness have been reported in some breastfed infants. Decreased infant weight gain was found in one study, but not in others. No adverse effects on development have been found in a few infants followed for up to a year. If fluoxetine is required by the mother, it is not a reason to discontinue breastfeeding. If the mother was taking fluoxetine 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 breastfed infant should be monitored for behavioral side effects such as colic, fussiness or sedation and for adequate weight gain. Mothers taking an SSRI during pregnancy and postpartum may have more difficulty breastfeeding, although this might be a reflection of their disease state.[1] These mothers may need additional breastfeeding support. Breastfed infants exposed to an SSRI during the third trimester of pregnancy have a lower risk of poor neonatal adaptation than formula-fed infants.

Possible effects of Fluoxetine on milk supply

Fluoxetine has caused increased prolactin levels and galactorrhea in nonpregnant, nonnursing patients.[32][33][34][35][36][37][38][39][40] Euprolactinemic galactorrhea has also been reported.[41] In a study of cases of hyperprolactinemia and its symptoms (e.g., gynecomastia) reported to a French pharmacovigilance center, fluoxetine was found to have a 3.6-fold increased risk of causing hyperprolactinemia compared to other drugs.[36] Preliminary animal and in vitro studies found that fluoxetine may have some estrogenic activity.[37] 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.[38]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.[39]An observational study looked at outcomes of 2859 women who took an antidepressant during the 2 years prior to pregnancy. Compared to women who did not take an antidepressant during pregnancy, mothers who took an antidepressant during all 3 trimesters of pregnancy were 37% less likely to be breastfeeding upon hospital discharge. Mothers who took an antidepressant only during the third trimester were 75% less likely to be breastfeeding at discharge. Those who took an antidepressant only during the first and second trimesters did not have a reduced likelihood of breastfeeding at discharge.[42] The antidepressants used by the mothers were not specified.A retrospective cohort study of hospital electronic medical records from 2001 to 2008 compared women who had been dispensed an antidepressant during late gestation (n = 575; fluoxetine n = 21) to those who had a psychiatric illness but did not receive an antidepressant (n = 1552) and mothers who did not have a psychiatric diagnosis (n = 30,535). Women who received an antidepressant were 37% less likely to be breastfeeding at discharge than women without a psychiatric diagnosis, but no less likely to be breastfeeding than untreated mothers with a psychiatric diagnosis.[43]

Possible alternatives to Fluoxetine

Nortriptyline, Paroxetine, Sertraline.

List of References

Lactation sources: Drugs and Lactation Database (LactMed) [Internet]. Bethesda (MD): National Library of Medicine (US); 2006-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK501922/1. Grzeskowiak LE, Leggett C, Costi L et al. Impact of serotonin reuptake inhibitor use on breast milk supply in mothers of preterm infants: A retrospective cohort study. Br J Clin Pharmacol. 2018;84:1373-9. PMID: 29522259
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. Heikkinen T, Ekblad U, Palo P et al. Pharmacokinetics of fluoxetine and norfluoxetine in pregnancy and lactation. Clin Pharmacol Ther. 2003;73:330-7. PMID: 12709723
4. 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
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. Kim J, Riggs KW, Misri S et al. Stereoselective disposition of fluoxetine and norfluoxetine during pregnancy and breast-feeding. Br J Clin Pharmacol. 2006;61:155-63. PMID: 16433870
7. Taddio A, Ito S, Koren G. Excretion of fluoxetine and its metabolite, norfluoxetine, in human breast milk. J Clin Pharmacol. 1996;36:42-7. PMID: 8932542
8. Kristensen JH, Ilett KF, Hackett LP et al. Distribution and excretion of fluoxetine and norfluoxetine in human milk. Br J Clin Pharmacol. 1999;48:521-7. PMID: 10583022
9. Tanoshima R, Bournissen FG, Tanigawara Y et al. Population PK modelling and simulation based on fluoxetine and norfluoxetine concentrations in milk: a milk concentration-based prediction model. Br J Clin Pharmacol. 2014;78:918-28. PMID: 24773313
10. Salazar FR, D’Avila FB, de Oliveira MH et al. Development and validation of a bioanalytical method for five antidepressants in human milk by LC-MS. J Pharm Biomed Anal. 2016;129:502-8. PMID: 27497651
11. Weisskopf E, Panchaud A, Nguyen KA et al. Simultaneous determination of selective serotonin reuptake inhibitors and their main metabolites in human breast milk by liquid chromatography-electrospray mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2017;1057: 101-9. PMID: 28511118
12. Lopes BR, Cassiano NM, Carvalho DM et al. Simultaneous quantification of fluoxetine and norfluoxetine in colostrum and mature human milk using a 2-dimensional liquid chromatography-tandem mass spectrometry system. J Pharm Biomed Anal. 2017;150:362-7. PMID: 29287263
13. Pogliani L, Baldelli S, Cattaneo D et al. Selective serotonin reuptake inhibitors passage into human milk of lactating women. J Matern Fetal Neonatal Med.2019;32:3020-25. PMID: 29557689
14. Epperson CN, Jatlow PI, Czarkowski K et al. Maternal fluoxetine treatment in the postpartum period: effects on platelet serotonin and plasma drug levels in breastfeeding mother-infant pairs. Pediatrics. 2003;112:e425-9. PMID: 14595087
15. Lester BM, Cucca J, Andreozzi L et al. Possible association between fluoxetine hydrochloride and colic in an infant. J Am Acad Child Adolesc Psychiatry. 1993;32:1253-5. PMID: 8282672
16. Isenberg KE. Excretion of fluoxetine in human breast milk. J Clin Psychiatry. 1990;51:169. Letter. PMID: 2324084
17. Rohan A. Drug distribution in human milk. Aust Prescriber. 1997;20:84.
18. Hale TW, Shum S, Grossberg M. Fluoxetine toxicity in a breastfed infant. Clin Pediatr. 2001;40:681-4. PMID: 11771923
19. Brent NB, Wisner KL. Fluoxetine and carbamazepine concentrations in a nursing mother/infant pair. Clin Pediatr. 1998;37:41-4. PMID: 9475699
20. Yoshida K, Smith B, Craggs M et al. Fluoxetine in breast-milk and developmental outcome of breast-fed infants. Br J Psychiatry. 1998;172:175-8. PMID: 9519072
21. Chambers CD, Anderson PO, Thomas RG et al. Weight gain in infants breastfed by mothers who take fluoxetine. Pediatrics. 1999;104:e61. PMID: 10545587
22. Moretti ME, Sharma A, Bar-Oz B et al. Fluoxetine and its effects on the nursing infant: a prospective cohort. Clin Pharmacol Ther. 1999;65:141. Abstract. DOI: doi:10.1016/S0009-9236(99)80095-2
23. Nulman I, Rovet J, Stewart DE et al. Child development following exposure to tricyclic antidepressants or fluoxetine throughout fetal life: a prospective, controlled study. Am J Psychiatry. 2002;159:1889-95. PMID: 12411224
24. 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
25. 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
26. 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
27. Rampono J, Kristensen JH, Ilett KF, Hackett LP, Kohan R. Quetiapine and breast feeding. Ann Pharmacother. 2007;41:711-4. PMID: 17374621
28. Hale TW, Kendall-Tackett K, Cong Z, Votta R, McCurdy F. Discontinuation syndrome in newborns whose mothers took antidepressants while pregnant or breastfeeding. Breastfeed Med. 2010;5:283-8. PMID: 20807106
29. Kieviet N, Hoppenbrouwers C, Dolman KM et al. Risk factors for poor neonatal adaptation after exposure to antidepressants in utero. Acta Paediatr. 2015;104:384-91. PMID: 25559357
30. Morris R, Matthes J. Serotonin syndrome in a breast-fed neonate. BMJ Case Rep. 2015. PMID: 25948853
31. Gashlin LZ, Sullo D, Lawrence RA et al. Treatment of narcolepsy with sodium oxybate while breastfeeding: A case report. Breastfeed Med. 2016;11:261-3. PMID: 27057786
32. Arya DK, Taylor WS. Lactation associated with fluoxetine treatment. Aust N Z J Psychiatry. 1995;29:697. Letter. PMID: 8825840
33. 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
34. Iancu I, Ratzoni G, Weitzman A et al. More fluoxetine experience. J Am Acad Child Adolesc Psychiatry. 1992;31:755-6. Letter. PMID: 1644743
35. Peterson MC. Reversible galactorrhea and prolactin elevation related to fluoxetine use. Mayo Clin Proc. 2001;76:215-6. PMID: 11213313
36. 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
37. Muller JC, Imazaki PH, Boareto AC et al. In vivo and in vitro estrogenic activity of the antidepressant fluoxetine. Reprod Toxicol. 2012;34:80-5. PMID: 22522098
38. 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
39. Gorman JR, Kao K, Chambers CD. Breastfeeding among women exposed to antidepressants during pregnancy. J Hum Lact. 2012;28:181-8. PMID: 22344850
40. Suthar N, Pareek V, Nebhinani N et al. Galactorrhea with antidepressants: A case series. Indian J Psychiatry. 2018;60:145-46. PMID: 29736080
41. Kaba D, Oner O. Galactorrhea after selective serotonin reuptake inhibitor use in an adolescent girl: A case report. J Clin Psychopharmacol. 2017;37:374-6. PMID: 28383361
42. Venkatesh KK, Castro VM, Perlis RH et al. Impact of antidepressant treatment during pregnancy on obstetric outcomes among women previously treated for depression: An observational cohort study. J Perinatol. 2017;37:1003-9. PMID: 28682318
43. Leggett C, Costi L, Morrison JL et al. Antidepressant use in late gestation and breastfeeding rates at discharge from hospital. J Hum Lact. 2017;33:701-9. PMID: 28984528

Disclaimer: This material is provided for educational purposes only and is not intended for medical advice, diagnosis, or treatment. Consult your healthcare provider with any questions.

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