This section is written for medical professionals.
For consumer information, see Fact sheet on fluoxetine
- Licensed in New Zealand for treatment of depression, bulimia nervosa, obsessive compulsive disorder, and premenstrual dysphoric disorder ( a severe form of PMS ).
- Available as Fluox and Prozac 20.
- Last updated: November 2010.
- might possibly be associated with a very small absolute risk of cardiac congenital malformations.
- has a relatively low incidence of neonatal adaption syndrome compared with paroxetine or venlafaxine.
- is not recommended during breastfeeding.
The decision to use psychotropic medication in preganancy and breast feeding should be made weighing up the risks versus the benefits in each individual case. It should involve an informed choice between patient and clinician.
Use in Pregnancy
- Fluoxetine is the SSRI that has been most extensively studied in pregnancy.
- Many reviews (1, 2, 3, 4) have suggested that SSRIs as a class do not increase the risk of common birth defects, although individual SSRIs may confer a small increased risk of congenital cardiac malformations.
- A prospective multi-centred controlled observational study (5) demonstrated use of fluoxetine or paroxetine in the first trimester was associated with an increased risk of anomalies in the infant (they were diverse range).
- Further, the authors found that the use of fluoxetine in the first trimester and smoking greater than 10 cigarettes daily was associated with a further substantial risk for cardiovascular anomalies in the infant.
- This possible increase in risk of birth defects for fluoxetine had been also investigated in a large (n=493,113) population-based cohort study in Denmark (6). They found an increased prevalence of septal heart defects among children whose mothers were prescribed an SSRI (n=1,370) in early pregnancy, particularly for sertraline and citalopram. The absolute increase in prevalence of septal heart defects was low with any SSRI (0.9% vs 0.5% amongst unexposed children). For specific SSRIs the prevalence of septal heart defects were 0.6% for fluoxetine (almost near natural un-exposed baseline risk) , 1.1% for citalopram and 1.5% for Sertraline. It is unknown how many of these defects required surgery.
- There was no significant difference in major malformations or non cardiac malformations between SSRI and unexposed groups.
- In addition, children of women who were prescribed more than one type of SSRI during pregnancy had a 4-fold increased risk of septal heart defects -suggesting that simultaneous use of different SSRIs or a change in type of SSRI during pregnancy may be problematic.
- In a systemic review of antidepressants in pregnancy (19), 35 articles relating to congenital malformations were identified. Of these, 12 identified a significant association between antidepressnt use in early pregnancy and congenital malformations but 23 did not demonstarte this association. Many of these studies had significant limitations.
- SSRIs as a class may increase the risk of preterm delivery, low birth weight and low apgar scores (7).
- Neonatal adaption syndrome (NAS) can occur in infants of mothers who have used SSRIs near term (8). It is not certain whether this is due to perinatal toxicity or a discontinuation syndrome (9, 10). Generally NAS symptoms in the newborn infant resolve spontaneously. There have been no reported deaths or ongoing complications from NAS (8), however occasional specific or supportive treatment in intensive care units have been required.
- The incidence of NAS is reported to be around 30% for SSRIs as a group(11).
- Among cases of adverse drug reactions reported to the World Health Organisation (WHO), fluoxetine was associated with 14 of the 93 cases(15%) of suspected SSRI-induced NAS (18).
- A possible increased risk of persistent pulmonary hypertension (PPH) in infants exposed to SSRIs after 20 weeks duration has been identified (12). This study did not have enough statistical power to differentiate between the SSRIs, but did identify an absolute increase in risk of 5 cases per 1,000 exposures.
- There is a theoretical concern about long term neurobehavioural effects in infants following exposure to SSRIs in-utero. No differences were seen in infant development (compared to those that had not been exposed) during a 4-5 year follow-up (13). However a study (14) evaluating the association between antidepressant exposure (predominantly SSRIs) in-utero and achievement of developmental milestones found a near 16 day delay in ability to sit, a 29 day delay in walking and fewer could occupy themselves at 18 months of age compared to those that had not been exposed to antidepressants. It should be noted that these delays in milestones were still within normal range of development and that there were a number of confounders in the study (uncertain degree of illness severity in the mothers, lack of blinding of participants and interviewers and not all participants completing all the interviews).
Use in Lactation
Category L3 for neonates, L2 for older infants
- As a rule, fluoxetine is the least preferred SSRI in breastfeeding, especially for a newborn infants.
- This is because fluoxetine, and its metabolite norfluoxetine, have a long half life and may accumulate in the infant.
- Fluoxetine produced the highest proportion of infant levels (above that theoretical safe level of 10% of maternal concentration) following prenatal exposure (15). Although no adverse events were found (2), there have been reports of colic, prolonged crying and mild seizures (16).
- Reduced postnatal growth in fluoxetine exposed infants was found in one study (17).
(1) Louik C., et al. First trimester use of selective serotonin reuptake inhibitors and the risk of birth defects. N
Engl J Med (2007) 356(26): 2675-2683.
(2) Gentile, S. The safety of newer antidepressants in pregnancy and breastfeeding. Drug Safety (2005) 28(2):
(3) Kallen, BA.; Otterblad Olausson, P. Maternal drug use in early pregnancy and infant cardiovascular defect.
Reproductive Toxicology (2003) 17(3): 255-261.
(4) Einarson, TR; Einarson, A. Newer antidepressants in pregnancy and rates of major malformations: a metaanalysis
of prospective comparative studies. Pharmacoepidem & Drug Safety (2005) 14(12): 823-827.
(5) Diav-Citrin, O. et al. Paroxetine and Fluoxetine in pregnancy: a prospective, multicentred, controlled,
observatinal study. Br J Pharmcol (2008) 66(5): 695-705.
(6) Pedersen, L.H., et al. Selective serotonin reuptake inhibitors in pregnancy and congenital malformations:
population based cohort study. BMJ (2009) 339: b3569.
(7) Kallen, B. Neonate characteristics after maternal use of antidepressants in late pregnancy. Arch Ped Adol
Med (2004) 158(4): 312-316.
(8) Koren, G., et al. Is maternal use of selective serotonin reuptake inhibitors in the third trimester of pregnancy
harmful to neonates? Can Med Ass J (2005) 172: 1457-1459.
(9) Gentile, S., et al. SSRIs in breastfeeding: spotlight on milk to plasma ratio. Arch Womens Ment Health (2007)
(10) ter Horst, P.G.J., et al. Pharmacological aspects of neonatal antidepressant withdrawal. Obstet Gynecol
Survey (2008) 63(4): 267-279.
(11) Levinson-Castiel, et al. Neonatal abstinence syndrome after in-utero exposure to selective serotonin
reuptake inhibitors in term infants. Arch Ped Adol Med (2006) 160: 173-176.
(12) Chambers, C.D., et al. Selective serotonin-reuptake inhibitors and risk of persistent pulmonary hypertension
of the newborn. N Eng J Med (2006) 354(6): 579-589.
(13) Rubinow D.R. Antidepressant treatment during pregnancy: between Scylla and Cahribdis. Am J Psychiatry
(2006) 163: 954-956.
(14) Pedersen, L.H., et al. Fetal exposure to antidepressants and normal milestone development at 6 and 19
months of age. Pediatrics (2010) 125: e600-e608.
(15) Weissman, AM., et al. Pooled analysis of antidepressant levels in lactating mothers, breast milk and nursing
infants. Am J Psych (2004) 161(6): 1066-1078.
(16) Malone, K., et al. Antidepressants, antipsychotics, benzodiazepines, and the breastfeeding dyad. Perspect
in Psych Care (2004) 40(2): 73-85.
(17) Chambers, CD., et al. Weight gain in infants breastfed by mothers who take Fluoxetine. Pediatrics (1999)
(18) Sanz, FJ., et al. Selective serotonin reuptake inhibitors in pregnant women and neonatal withdrawal
syndrome: a database analysis. Lancet (2005) 365(9458): 482-487.
(19) Udechuku,A., Nguyen T., Hill R., Szego K. Antidepressants in pregnancy: a systematic review. Australian and New Zealand Journal of psychiatry (2010) 44:978-996.