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Treating a Major Depressive Episode during Pregnancy

The following treatment guidelines are meant as a reference tool only, and are not intended as treatment advice or to replace the clinical decision-making process of psychiatrists or other health professionals who administer these treatments. In clinical practice there are often good reasons why treatment approaches differ from what is described here.


Safety Concerns of Antidepressants in Pregnancy

The safety of antidepressants during pregnancy remains an important but controversial subject. Despite the many studies that have been done in this area, there are still no firm conclusions about the exact risks of taking antidepressants during pregnancy. This has to do with ethical concerns that limit the kinds of studies that can be done on this topic, the fact that Depression on its own can have negative consequences on the course of a pregnancy [ref, ref, ref, ref, ref], and that depressed women are also more likely to smoke and use alcohol and street drugs during pregnancy, which confounds the issue [ref].

The following are some of the possible concerns of using antidepressants in pregnancy that have been raised by certain studies:

Miscarriage rates may be slightly higher among women who use antidepressants compared with those who do not [ref].

Use of SSRIs in pregnancy may increase very slightly the risk of low birth weight of the newborn [ref, ref].

Antidepressants may shorten the duration of pregnancy on average by one week or less, and thus slightly increase the risk of preterm births. This risk may be greater the longer that the antidepressant is used during pregnancy [ref, ref], and can affect up to 20% of women who take SSRIs throughout their pregnancy, though untreated Depression can lead to similar rates [ref].

SSRI antidepressants can cause cardiac septal defects, which is a congenital malformation of the heart, in 0.9% of cases when used in pregnancy [ref]. In the general population (when not using antidepressants) the risk of these defects in pregnancy is 0.5%, and when more than one SSRI is used in the pregnancy the risk of these defects is 2.1% [ref]. Paroxetine in particular has been identified in a few studies as increasing the risk of congenital heart defects [ref, ref, ref], and Fluoxetine has also been implicated [ref].

Prolonged SSRI use has been associated with respiratory problems at birth [ref]. The most severe form of this problem is Persistent Pulmonary Hypertension (PPH), which can result in the death of the baby in 10% of cases. There may be up to a 1.2% chance that a newborn will have PPH if an SSRI was used after week 20 of pregnancy [ref, ref]. In the general population (when not using antidepressants) the risk of a child being born with PPH is 0.2%. 

If antidepressants are used in the third trimester and up to delivery, there is a chance of 20-30% that the newborn will experience a set of symptoms known as poor neonatal adaptation, which includes irritability, muscle stiffness, jitteriness, feeding difficulties, tremors, agitation, and trouble breathing, among others [ref].  These symptoms are usually mild and disappear within 2 weeks.  They are thought to occur as a result of the newborn withdrawing from the antidepressantParoxetine has the highest risk of causing this syndrome [ref].   In about 0.3% of these cases, this syndrome can be severe enough to cause seizures and respiratory distress (serious breathing problems) [ref].

Use of SSRIs in the third trimester has been associated with an increased risk for high blood pressure and pre-eclampsia in the mother [ref].

It has been found that amniotic fluid concentrations of antidepressants vary widely, and in some cases these concentrations can be higher than in maternal blood [ref].

There is no evidence that antidepressants used in pregnancy cause any long-term problems in children, such as learning, behavioral or emotional problems [ref].

A Treatment Approach for Depression in Pregnancy

Given these possible risks from medications, it is recommended that psychotherapy be considered as a first choice either for preventing or treating a Depression during pregnancy [ref]. The same kinds of psychotherapy for Depression that are generally recommended would be expected to work for pregnant women.

If psychotherapy is tried and found not to provide enough help, or if for various reasons it is not a good option for a particular mother, then antidepressants should be considered.  In cases of severe Depression, especially where the women is experiencing suicidal tendencies or psychosis (or has experienced similar episodes in the past), medications should be strongly considered, for in these cases the risks that the Depressive Episode poses to the mother likely outweigh the possible risks of medication exposure to the fetus.

When considering the use of antidepressants during pregnancy, the risks must be weighed against those of leaving the Depression untreated, which can have significant negative consequences for the fetus and the mother. Also, women with Major Depressive Disorder who stop their antidepressants near the beginning of a pregnancy have a high risk of relapsing into Depression during the pregnancy [ref]; this is most true for women with a highly recurrent illness (more than 4 episodes in the past) or lengthy illness (longer than 5 years).       

In general, if considering the use of antidepressants and other medications for depression in pregnancy, the approach can be the same as for treating a Major Depressive Episode, or, as the case may be, treating an episode of Depression with psychosis, but with the following caveats:

It may be prudent to avoid Paroxetine given its association in some studies with congenital heart defects [ref].

In Step 2, Lithium should be avoided, especially during the first trimester, and all other medications should be used with caution and only after carefully verifying their safety information.  

If antipsychotic medications are required for treating an episode of depression with psychosis, it should be noted that there is somewhat better safety information regarding the use of Typical Antipsychotics in pregnancy as opposed to Atypical Antipsychotics, given that the Typicals have been in use for longer.

ECT is considered effective and safe for use in pregnancy [ref, ref] and should be strongly considered especially in severe cases where other treatments are not effective or desired.

When using medications during pregnancy, doses may need to be increased at around 27 weeks in order to maintain a constant level of the medication in the mother's circulation.


Unless otherwise indicated, the above recommendation are based on the treatment guidelines developed by the American Psychiatric Association and the American College of Obstetricians and Gynecologists [ref].


In Children and Adolescents

Postpartum Depression