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Summary

In this study, the risk of relapse in pregnant women who discontinued their antidepressant medication around the time of conception was examined. A total of 201 pregnant women with a history of depression who were taking antidepressants were observed from the time that they decided to either continue or discontinue their medications. Participants had to fulfill the following criteria:

  • History of major depression prior to becoming pregnant;
  • Within the first 16 weeks' gestation at start of study;
  • Euthymia for at least 3 months prior to last menstrual period; and
  • Currently receiving antidepressant medications.

Patients were classified into 4 groups: (1) those who maintained their current antidepressant dosage, (2) those who decreased their dosage, (3) those who increased their dosage, and (4) those who discontinued their medication altogether.

The investigators found that of the original 201 participants, 86 (43%) experienced a relapse of their depressive illness. Of the women who discontinued their antidepressants, 44/65 (68%) suffered a relapse compared with 21/82 (26%) of those who maintained their antidepressants. Using Cox proportional hazards, women who discontinued their medication had 5 times the risk for relapse compared with those who maintained antidepressants at their pre-pregnancy dose. Of the group who decreased their dosage, 12/34 (35.3%) relapsed compared with 9/20 (45%) of those who increased their dose.

For patients who relapsed, the majority did so during the first trimester. The group who increased their medications probably did so in response to symptoms of depression that initially did not rise to the level of full major depressive diagnosis, but did represent residual symptoms that made them vulnerable for relapse. This study supports that pregnancy is not "protective" in preventing relapse of depressive episodes in women with a history of depression.

Viewpoint

Treatment of depression in pregnant woman is complex. The risk of problems caused by antidepressant medications to the fetus must be weighed against the risk for relapse to the mother. In the past, conventional wisdom indicated that pregnancy seemed to have a "protective" quality in preventing depression. The results of this study by Cohen and colleagues indicate that for women with a history of major depression, relapse is fairly common, especially in those who discontinue their antidepressant medications.

Until recently, data supporting an increased risk of congenital malformations from antidepressant medications did not exist. Several recent unpublished reports (made public by the manufacturers of paroxetine),[1] however, indicate a possible increased risk for ventricular and atrial-septal defects in children of women who took this antidepressant during the first trimester. Thus, the US Food and Drug Administration has issued a warning in this regard for paroxetine.[2]

Other reports have described symptoms of neonatal jitteriness and distress in infants whose mothers were on antidepressant medications at the time of their delivery.[3,4] On the other hand, maternal depression has the definite potential of deleterious effect on the fetus as well.

Patients in this trial were treated and observed at 3 medical sites with known expertise in the treatment of psychiatric conditions in pregnant women. The participants in this study had a high number of previous depressive episodes; more than 75% of them had at least 3 previous episodes. This study really does not help delineate the risk for the more typical patient in a primary care setting who is being treated for her initial depressive episode or who may have only 1 previous episode. The risk for this group might be considerably lower than that for the cohort that was studied. Nevertheless, this study is a valuable addition to our understanding of the risks for depressive relapse in pregnant women who either continue or discontinue their antidepressant medications; the trial provides information for clinicians to share with depressed women taking antidepressants who are planning to become or have become pregnant.

 

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