According to a statement from the American College of Obstetricians and Gynecologists (ACOG) reaffirmed in 2014, the absolute risks of birth defects associated with selective serotonin reuptake inhibitors (SSRIs) use were identified in some case-control studies were not significant or small. However, the risk of depression relapse upon treatment discontinuation should be considered. Therefore, SSRIs or serotonin and norepinephrine reuptake inhibitors (SNRIs) therapy during pregnancy should be individualized (Level C recommendation). Of note, paroxetine (Paxil) should be avoided in pregnant women and women who plan to become pregnant (Level B recommendation). [1]
A 2015 systematic review assessed the safety of SSRIs and SNRIs on neonates when used by nursing mothers. For SSRIs, the review included 112 neonates exposed to citalopram, 37 to escitalopram, 280 to fluoxetine, 18 to fluvoxamine, 228 to paroxetine, and 279 to sertraline. For SNRIs, there were 8 infants exposed to duloxetine and 41 to venlafaxine. Most of the literature was a compilation of case reports or studies with a small sample size. Adverse events to neonatal fluoxetine exposure through breast milk were seen in 11 out of 280 cases. These adverse events included two cases of colic; one case of possible seizure;one case of irritability and restlessness (subsided after breastfeeding stopped); one case of somnolence, lethargy, fever, and unresponsiveness; and one case of watery stool, uncontrollable crying, vomiting, and poor sleeping. The relative infant dose (RID) with fluoxetine ranged from 0.54% to 6.81%, which was more elevated compared to other SSRIs but still below the recommended safety limit of 10%. The milk-to-plasma ratio, in studies where it was evaluated, ranged from 0.01 to 6.09 for fluoxetine and from 0.08 to 2.08 for its metabolite norfluoxetine. A detectable neonate plasma drug concentration (NPDC) of fluoxetine (1-304 ng/mL) was discovered in 41 infants and of norfluoxetine in 82 infants (1.4-640 ng/mL). Milk drug concentration (MDC) of fluoxetine was detected in 109 infants (3-578 ng/mL) and MDC of norfluoxetine in 105 infants (2-314 ng/mL). Two cases reported adverse events in neonates due to paroxetine use. The RID with paroxetine ranged from 0.34% to 3%, and detectable serum concentration in infants was found in only three studies. The MDC of paroxetine was 2-776 ng/mL, as detected in 8 out of 17 studies. The milk-to-plasma ratio was evaluated in 9 studies and ranged from 0.056 to 1.3 ng/mL. The RID with sertraline ranged from 0.54% to 2.2% with a detectable serum concentration found in 10 of 279 infants (2-87 ng/mL) and in 27 cases for its metabolite norsertraline (NSER) (15-7,897 ng/mL). The milk-to-plasma ratio ranged from 0.42 to 4.81 for both sertraline and its metabolite. Data from this review suggest that paroxetine and sertraline have the best safety profiles for exposed infants, and these should be the preferred first-line agents when the use of SSRI is indicated in a nursing woman. [2]
A 2018 review of clinical practice guidelines for perinatal depression identified 16 guidelines in 12 countries. The authors found 4 guidelines advised to continue antidepressants. Five guidelines do not specifically advise or discourage continuation. For new episodes, guidelines agree on psychotherapy (especially cognitive behavioral therapy) as initial treatment for mild to moderate depression and on antidepressants for severe depression, with a preference for sertraline. Paroxetine is not the preferred treatment for new episodes, but switching antidepressants for ongoing treatment is discouraged (3 guidelines). If mothers use antidepressants, observation of the neonate and breastfeeding when possible is generally recommended by all guidelines. [3]
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. [4]
Additionally, if a mother is taking fluoxetine during pregnancy or if other antidepressants have been ineffective, it is not recommended to change medications during breastfeeding. However, agents with lower excretion into breast milk may be preferred when nursing a newborn or preterm infant. [4]
A case report describes a late preterm infant that presented with tachypnea, jitteriness, irritability and low grade fever. Blood gas also identified compensated metabolic acidosis. The patient’s mother was taking fluoxetine 60 mg/day and was exclusively breastfeeding. Serum levels of fluoxetine within the adult therapeutic range were found on day 8 in the baby. After changing to formula feeds, symptoms resolved. It was determined the baby’s symptoms were due to SSRI toxicity. Although the lack of clinical data made it difficult to establish the diagnosis and to determine what is considered high dose for the mother. [5]