Clinical Review

A talk about, then a plan for, antidepressants in pregnancy

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Start? Stop? Sustain? Switch? How should you advise a patient about a serotonin reuptake inhibitor during pregnancy—for her health and the well being of the fetus?


 

References

CAS: Depressive disorder, anticipating a pregnancy

Your patient Megan—well-educated, 29 years old, G0P0—has come to you to discuss her antidepressant (paroxetine [Paxil]) because she is planning her first pregnancy.

Megan has a history of recurrent major depressive disorder (MDD), which is in remission (see “What is MDD?”).

How will you begin the conversation with this patient about keeping MDD in remission during her pregnancy and ensuring the safety of her fetus?

What is MDD?
  • Major depressive disorder (MDD) is defined by criteria in the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV)
  • The disorder varies in severity, 1) across an affected person’s lifetime and 2) within a depressive episode
  • A current or prior episode of depression that includes 1) a significant impact on an individual’s functioning, 2) active suicidality, or 3) hospitalization signals severe MDD
  • In women, average age at first episode of depression is 24 years

There is a 20% to 25% lifetime prevalence of depression in women; the disorder peaks during childbearing years, however.1 As of 2003, 13% of pregnant women had taken an antidepressant at some time during their pregnancy, a percentage that has doubled since it was assessed in 1999.2

You are faced with several quandaries in deciding whether to recommend that your patient continue, or discontinue, antidepressant therapy during pregnancy:

  • As many as 68% of women who terminate antidepressant treatment before or during pregnancy relapse.
  • Even 26% of women who continue antidepressant during pregnancy relapse—requiring a dosage adjustment or change in treatment.3
  • Yet the possibly elevated cortisol levels of severe, untreated depression may harm the placenta and fetus.4,5

So, what do you need to know to assess the risks and benefits of “Megan” stopping, or continuing, paroxetine during her anticipated pregnancy? And what are the risks to Megan’s fetus of treating, or not treating, her depression with a serotonin reuptake inhibitor (SRI*)?

*Terminology has changed:
“Selective” has been dropped
from “SSRI” to yield simply “SRI.”

Gauging the risks of depression in pregnancy

In any given patient, her history and family history of depression are key to determining the likelihood that she will suffer ongoing or recurrent depression.

CASE continued Repeated treated episodes plus a family history

In obtaining Megan’s history, you learn that she has had three prior episodes of depression, all of which were successfully treated with paroxetine. Megan has been stable on paroxetine for 3 years.

Notably, the second episode of depression was initially treated with a 16-week trial of psychotherapy alone; when depressive symptoms did not remit, paroxetine was added. That episode was considered severe because it included pervasive thoughts of suicide.

You also learn that Megan’s mother suffered from postpartum depression and that her father and paternal grandmother were treated for depression.

Known risk factors for depression during pregnancy include: maternal anxiety; prior diagnosis of depression during pregnancy; history of postpartum anxiety or depression; prior diagnosis of either anxiety or depressive disorder; significant life stress (e.g., divorce, death of a loved one); degree of social support—particularly, intimate social support; “intendedness” of pregnancy; domestic violence; and insurance status.6

You review with Megan her risk factors for depression during pregnancy, namely: three prior episodes of MDD and a strong family history of mood disorder. Her MDD is considered “severe” because she has a history of suicidality. You tell Megan that, given these factors, she is at high risk of a recurrence of her depressive illness during pregnancy.

Megan asks: “Would getting depressed during pregnancy hurt the baby?”

Depression during pregnancy affects both infant and maternal well-being, although studies are in conflict about the extent of that morbidity. Multiple areas of potential risk to mother and infant have been studied, including the effect of depression on:

  • maternal well-being
  • growth of the infant
  • spontaneous abortion
  • preterm delivery
  • neonatal physiologic and neurobehavioral measures
  • long-term considerations for the developing infant and child.

Within these categories of risk, a diagnosis of depression during pregnancy has been associated (in some but not all studies) with a higher risk, or rate, of:

  • postpartum depression
  • preterm birth
  • lower maternal weight gain
  • maternal tobacco, alcohol, and other substance use
  • lower infant gestational age at birth
  • small-for-gestational age infant birth.7-10

In terms of long-term impact on offspring, studies differ in their estimation of risk; however, children exposed to untreated, maternal depression at 18 weeks’ and 32 weeks’ gestation did show a greater degree of developmental delay at 18 months than children who were born to a mother who was not depressed during pregnancy.11

You discuss these risks with Megan. She asks: “What treatment do you recommend for me?” You turn to the 2009 guidelines published jointly by the American Psychiatric Association (APA) and ACOG.

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