This section is designed to inform professionals.
(Consumers, see Fact Sheet on Fluoxetine)
Available as Fluox and Prozac.
Use in Pregnancy
- Fluoxetine is the SSRI most extensively studied in pregnancy.
- Studies show no increase in either major malformations or spontaneous abortions rates (1) (2) (3).
- No correlation between SSRIs in general and increased risk of malformations was found (4) (5) (6).
- A report of an association with minor malformations (7) lacks clinical data and is difficult to assess.
- A study of children who had been exposed to Fluoxetine in utero (including first trimester exposure) showed normal neurodevelopment at preschool age (8).
- One study of third trimester Fluoxetine exposure (9) showed no significant increase in postnatal complications
However, studies of antidepressants or SSRIs in general have raised the following concerns:
- Exposure to antidepressants may increase the risk of preterm delivery, low birth weight and low Apgar score, as was found in one large study (10), which also found that other outcomes (hypoglycemia, neonatal convulsions and respiratory distress) were increased with antidepressant use (although not as much with SSRIs compared to tricyclics).
- One study (11) suggests that there may be a risk of persistent pulmonary hypertension (PPH) in infants exposed to SSRIs after 20 weeks gestation. The absolute increase in risk in this study was 5 cases per 1,000 exposures. This study did not have sufficient statistical power to differentiate between different SSRIs. The potential risk of PPH has not been confirmed by additional studies. Uncertainty about these rare events needs to be weighed against the potential risk of recurring depression if the mother stops Fluoxetine. (12)
- Babies exposed to SSRIs in utero are at risk of neonatal adaptation syndrome. The incidence of this syndrome is reported to be around 30% for SSRIs in general (13). Among cases of adverse drug reactions reported to the World Health Organization (WHO), Fluoxetine was associated with 14 of the 93 cases of suspected SSRI-induced neonatal withdrawal syndrome (14).
Use in Lactation
Category L3 for neonates, L2 for older infants
- Fluoxetine is the least preferred SSRI in breastfeeding, especially for newborn infants.
- Fluoxetine and especially its metabolite norfluoxetine (with very long half-life) may be detected in infant serum.
- In a review of antidepressants in breastfeeding infants, Fluoxetine produced the highest proportion of infant levels elevated above 10% of the maternal level, especially following prenatal exposure (15).
- No adverse events were found in several studies (3). There have been a few case reports of colic, prolonged crying, mild seizures (16), vomiting, tremulousness and other symptoms, although the number of these case reports is very small compared to the thousands of infants exposed to Fluoxetine through breastfeeding without side effects.
- Reduced postnatal growth in Fluoxetine-exposed infants was found in one study. (17)
(1) Addis A. Koren G. Safety of Fluoxetine during the first trimester of pregnancy: a meta-analytical review of epidemiological studies. Psychological Medicine. 30(1):89-94, 2000 Jan.
(2) Goldstein DJ. Corbin LA. Sundell KL. Effects of first-trimester Fluoxetine exposure on the newborn. Obstetrics & Gynecology. 89(5 Pt 1):713-8, 1997 May.
(3) Gentile S. The safety of newer antidepressants in pregnancy and breastfeeding. Drug Safety. 28(2):137-52, 2005.
(4) McElhatton PR. Garbis HM. Elefant E. Vial T. Bellemin B. Mastroiacovo P. Arnon J. Rodriguez-Pinilla E. Schaefer C. Pexieder T. Merlob P. Dal Verme S. The outcome of pregnancy in 689 women exposed to therapeutic doses of antidepressants. A collaborative study of the European Network of Teratology Information Services (ENTIS). Reproductive Toxicology. 10(4):285-94, 1996 Jul-Aug.\
(5) Kallen BA. Otterblad Olausson P. Maternal drug use in early pregnancy and infant cardiovascular defect. Reproductive Toxicology. 17(3):255-61, 2003 May-Jun.
(6) Einarson TR. Einarson A. Newer antidepressants in pregnancy and rates of major malformations: a meta-analysis of prospective comparative studies. Pharmacoepidemiology & Drug Safety. 14(12):823-7, 2005 Dec
(7) Chambers CD. Johnson KA. Dick LM. Felix RJ. Jones KL. Birth outcomes in pregnant women taking Fluoxetine. New England Journal of Medicine. 335(14):1010-5, 1996 Oct 3.
(8) Nulman I. Rovet J. Stewart DE. Wolpin J. Gardner HA. Theis JG. Kulin N. Koren G. Neurodevelopment of children exposed in utero to antidepressant drugs. New England Journal of Medicine. 336(4):258-62, 1997 Jan 23.
(9) Goldstein DJ. Effects of third trimester Fluoxetine exposure on the newborn. Journal of Clinical Psychopharmacology. 15(6):417-20, 1995 Dec.
(10) Kallen B. Neonate characteristics after maternal use of antidepressants in late pregnancy. Archives of Pediatrics & Adolescent Medicine. 158(4):312-6, 2004 Apr.
(11) Chambers CD. Hernandez-Diaz S. Van Marter LJ. Werler MM. Louik C. Jones KL. Mitchell AA. Selective serotonin-reuptake inhibitors and risk of persistent pulmonary hypertension of the newborn. New England Journal of Medicine. 354(6):579-87, 2006 Feb 9.
(12) FDA Public Health Advisory. Treatment Challenges of Depression in Pregnancy and the Possibility of Persistent Pulmonary Hypertension in Newborns. http://www.fda.gov/cder/drug/advisory/SSRI_PPHN200607.htm. Created 19 July 2006, retrieved 5 October 2007.
(13) Levinson-Castiel et al. Neonatal Abstinence Syndrome After in Utero Exposure to Selective Reuptake Inhibitors in Term Infants. Archives of Pediatric and Adolescence Medicine 206:160:173-176
(14) Sanz EJ. De-las-Cuevas C. Kiuru A. Bate A. Edwards R. Selective serotonin reuptake inhibitors in pregnant women and neonatal withdrawal syndrome: a database analysis. Lancet. 365(9458):482-7, 2005 Feb 5-11.
(15) 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. American Journal of Psychiatry. 161(6):1066-78, 2004 Jun.
(16) Malone K. Papagni K. Ramini S. Keltner NL. Antidepressants, antipsychotics, benzodiazepines, and the breastfeeding dyad. Perspectives in Psychiatric Care. 40(2):73-85, 2004 Apr-Jun.
(17) Chambers CD. Anderson PO. Thomas RG. Dick LM. Felix RJ. Johnson KA. Jones KL. Weight gain in infants breastfed by mothers who take Fluoxetine. Pediatrics. 104(5):e61, 1999 Nov.