SSRIs

Jul 26, 2018 | Articles

SSRIs

Are SSRIs safe during pregnancy?

This is a great question. Unfortunately, there is not a simple answer. SSRIs are not completely risk free, but neither is untreated maternal illness. Women should decide whether or not to take an SSRI during pregnancy after consultation with a perinatal psychiatric specialist. Together, they can evaluate the risks and benefits of taking an SSRI after considering the woman’s personal psychiatric history, preferences, and values.

Untreated maternal mental illness

Women with a history of depression who stop taking their antidepressant have a 70% chance their depression recurring during pregnancy (compared to a 25% chance for women who continue taking their antidepressant).[i] Depression during pregnancy has been linked to increased rates of miscarriage and exposure of a developing fetus to stress.[ii] It has also been linked to an increased risk of postpartum depression, which, in turn, can affect a mother’s bonding with her baby, her ability to tolerate breastfeeding, and her attention to her baby’s safety.[iii]

Anxiety during pregnancy has also been linked to bad outcomes. Research has found that prenatal anxiety is linked to a developing baby later having childhood emotional and behavioral problems.[iv]

Mental illness during pregnancy is risky, often—but not always—more risky than the use psychiatric medications.

SSRIs

SSRIs are one common antidepressant. They have been relatively well studied. Approximately 8% of pregnant women take an antidepressant during pregnancy and, most commonly, this antidepressant is an SSRI. There are six common SSRIs: citalopram (Celexa), escitalopram (Lexapro), fluoxetine (Prozac), fluvoxamine (Luvox), paroxetine (Paxil), and sertraline (Zoloft).[v]

Benefits of SSRIs in depression

Many women find SSRIs to be very helpful in treating depression. Some studies suggest that 60% of women will benefit from taking an antidepressant. Studies also suggest when women take an SSRI in addition to receiving regular psychotherapy, they have a greater chance of recovery from depression (perhaps ~30% increased chance). If a woman has benefitted in the past from an antidepressant, the likelihood of benefiting from an antidepressant during pregnancy is even greater than it would be in most women.[vi]

Benefits of SSRIs in anxiety

Many women also find SSRIs to be helpful in treating anxiety. For example, one study found that 60% of patients on sertraline experienced a decrease in anxiety. When SSRIs are combined with psychotherapy, the benefits of these treatments are even greater than the use of either treatment alone. One study found that 80% of patients who received both CBT and sertraline were “very much or much improved” compared to 60% of patients who received either CBT or sertraline alone. Some women try to treat their anxiety through psychotherapy only, but find that they continue to have significant anxiety. These women should consider taking an SSRI. Women often report that after starting an SSRI, they are able to more easily put the skills they’ve learned in psychotherapy into practice.[vii]

Risks of SSRIs

Prior to pregnancy

  • Side effects
    It is not possible to list all the possible side effects SSRIs may cause. However, most women are able to tolerate SSRIs. Starting these medications at a low dose and then gradually increasing the medication to an effective dose tends to decrease the risk of any possible side effects. Some side effects, like upset stomach or diarrhea, tend to resolve as the body acclimates to the medication. Other side effects, such as sexual dysfunction, tend to persist until the woman stops taking the medication.[viii]
  • Fertility
    Data regarding SSRIs in women with regards to fertility is encouraging. For example, in one scientific study, depressed infertile couples (meaning at least one partner was depressed) who received treatment for depression (e.g. 6 months of cognitive behavioral therapy, individual supportive therapy, and fluoxetine as needed) were 14 times more likely to become pregnant than those who did not receive treatment. While I would not conclude from this study that fluoxetine increases fertility, it seems likely that it at least it does not decrease fertility in women with depression. Additionally, most studies show that SSRI use in women does not affect the success of fertility treatments like IVF.[ix]

During pregnancy

  • Miscarriage
    The scientific data regarding SSRIs and the risk of miscarriage is, in general, quite reassuring. There are contradictory studies, so the quality of each study is important to consider. Some studies appear to show that women on SSRIs are slightly more likely to have a miscarriage, but on further inspection, the studies are better interpreted as showing that depression, not an SSRI, is what is associated with the increased risk. One possible exception to this may be paroxetine (Paxil), but even this is controversial.[x]
  • Congenital defects
    SSRIs are not considered major teratogens, certainly not like Accutane or Thalidomide. A casual google search may bring up poorly conducted studies, some of which suggest that SSRIs may be associated with congenital defects. One of the most common flaws in these studies occurs when the researchers compare women with depression on SSRIs to women without depression. A much better comparison for understanding the effect of SSRIs on fetal development is to compare women with depression on SSRIs to women with depression not on SSRIs. One of the best studies did exactly this when it compared ~8,000 women on SSRIs with ~13,000 women with depression not on SSRIs. This study found no increase in congenital defects with the possible exception of paroxetine, which was associated with a small increased risk of heart defects (1.4% vs 0.8%). It should be noted that any pregnancy carries a 3-5% risk of major congenital anomalies. While we cannot conclusively state that SSRIs have absolutely no risk of congenital birth defects, the risk, if present, is small and is often outweighed by the risks of not treating maternal depression.[xi]
  • Preterm birth
    SSRIs may reduce the gestation period. However, studies suggest that the average reduction is about three days. This is unlikely to have a meaningful impact on a baby’s development.[xii]
  • Birth weight
    Evidence suggests that depression, but not SSRI use, may be linked to slightly lower birth weight.[xiii]

At delivery

  • Postpartum hemorrhage
    SSRIs have been associated with an increased risk of postpartum hemorrhage. Any pregnancy carries a 3% chance of postpartum hemorrhage. Use of an SSRI increases this risk to about 4%. Postpartum hemorrhage in developed countries has a low mortality rate (~0.05%). Thus, in the developed world, the risk of death from postpartum hemorrhage is about 1 in 70,000. For women on SSRIs, the risk is increased to about 1 in 50,000.[xiv]
  • Neonatal adaptation syndrome
    Babies born to mothers on SSRIs have an increased risk of a syndrome called “Neonatal adaptation syndrome.” This syndrome is generally mild and short-lived, resolving within two weeks but sometimes lasting up to one month. Babies with this syndrome may appear restless or irritable. They may not feed as well. These cases generally resolve without medical intervention. Severe cases are rare, but these cases can include seizures (0.7% of births of women on SSRIs) or respiratory distress (14% of births of women on SSRIs versus 8% of births of women not on SSRIs). Because severe cases may require medical intervention, women on SSRIs should deliver in a hospital. I also recommend that women on SSRIs remain in the hospital with their infant for 48 hours after delivery. That said, doctors in other medical specialties may find this recommendation overly conservative.[xv]
  • Persistent pulmonary hypertension of the newborn
    Persistent pulmonary hypertension of the newborn (PPHN) is a serious condition that occurs in approximately 2 of 1000 newborns. It is rare. Untreated, it is frequently fatal. Some studies have associated SSRIs with this condition. Newborns of mothers who have taken SSRIs in late pregnancy may be twice as likely to develop the condition. Part of his risk may be related to the mother having depression, but part of the risk may be attributable to the SSRI itself. That said, the FDA recommended in 2011 that physicians not to change their practice because the association was not clear. It stated that it “does not find sufficient evidence to conclude that SSRI use causes PPHN.” Additionally, while a risk being doubled is concerning, the absolute increased risk of this condition is still very small. Other risk factors have a much greater association with the condition. For example, the risks of PPHN are doubled (x2) in women who identify as black or Asian and in babies born after 41 weeks. It is quintupled (x5) in women who have taken aspirin, sextupled (x6) in women who have taken NSAIDs (like ibuprofen), and septupled (x7) in babies delivered by Caesarean section. Again, possible risks of medication must be weighed against known risks of untreated maternal illness.[xvi]

After delivery

  • Future development of the baby
    Many studies have examined whether or not maternal SSRI use during pregnancy is associated with babies having poor development later in life. In general, these studies are reassuring. SSRIs are unlikely to cause growth delays, abnormal development of motor skills, general cognitive delays, decreased intelligence, intellectual disability, or decreased scholastic achievement. Risks of impaired language development are small to nonexistent. While some studies that received media attention suggested that there might be an associated between maternal SSRI use and children developing autism, this possibility was later examined by multiple studies and found to be unlikely.[xvii]
  • Breastfeeding
    Breastfeeding is permissible while taking SSRIs. While SSRIs can be passed into a mother’s breastmilk, the levels of the drug to which babies are exposed can be quite low. For example, when the serum of infants has been examined, mothers who are breastfeeding on sertraline generally pass on so little to their infant that researchers cannot detect sertraline or its metabolites in 70% of infants. Other SSRIs can be found in greater abundance in infants’ serum, but many experts consider the benefit women receive from SSRIs to far outweigh the risks posed by exposure of the baby to the drug through breastfeeding.[xviii]

 

Summary

SSRIs during pregnancy are not entirely risk free, but neither is untreated maternal mental illness. Women should decide whether or not to take an SSRI during pregnancy after consultation with a perinatal psychiatric specialist. Together, they can evaluate the risks and benefits of taking an SSRI after considering the woman’s personal psychiatric history, preferences, and values.

 

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