Postpartum depression occurs in 14.5% of women in the first three months after birth. This study was an 8 week acute phase randomized trial with three cells (transdermal estradiol (E2), sertraline, and placebo) for the treatment of postpartum major depressive disorder. However, the study was stopped after batch analysis revealed that the E2 serum concentrations were lower than pre-study projections. This paper explores our experiences that will inform future investigations of therapeutic E2 use. Explanations for the low E2 concentrations were: 1) Study patch non-adhesion, which did not explain the low concentrations across the entire sample. 2) Ineffective transdermal patch preparations, although two different patch preparations were used and no significant main effect of patch type on E2 concentrations was found. 3) Obesity, at study entry, E2-treated women had mean ± SD BMI=32.9 ±7.4. No pharmacokinetic data comparing E2 concentrations from transdermal patches in obese women vs. normal weight controls are available. 4) Induction of Cytochrome P450 (CYP450) 3A4 and other E2 elimination pathways in pregnancy. CYP4503A4 is induced in pregnancy and is a pathway for the metabolism of E2. Conversion to estrone and Phase II metabolism via glucuronidation and sulfation, which also increase in pregnancy, are routes of E2 elimination. The time required for these pathways to normalize after delivery has not been elucidated. The observation that transdermal E2 doses greater than 100 mcg/day did not increase serum concentrations was unexpected. Another hypothesis consistent with this observation is suppression of endogenous E2 secretion with increasing exogenous E2 dosing.
Background
Women with Bipolar Disorder (BD) are at high risk for postpartum affective episodes and psychosis. Although validated screening tools are available for postpartum unipolar depression, few screening tools for hypomania/mania exist. Screening tools for BD in the postpartum period are essential for improving detection and planning appropriate treatment. We evaluated whether adding the Mood Disorders Questionnaire (MDQ) to the Edinburgh Postnatal Depression Scale (EPDS) increased the identification of BD in the early postpartum period.
Methods
Women (N=1279) who delivered a live infant and screened positive on the EPDS and/or MDQ at 4–6 weeks post-birth were invited to undergo an in-home Structured Clinical Interview for DSM-IV (SCID).
Results
Positive EPDS and/or MDQ screens occurred in 12% of the sample (n=155). In home SCID diagnostic interviews were completed in 93 (60%) of the mothers with positive screens. BD was the primary diagnosis in 37% (n=34). Women with BD screened positive on the EPDS and/or MDQ as follows: EPDS+/MDQ+ (n=14), EPDS+/MDQ− (n=17), and EPDS−/MDQ+ (n=3). The MDQ identified 50% (17/34) of the women with BD and 6 additional cases of BD when the MDQ question regarding how impaired the mother perceived herself was excluded from the screen criterion.
Conclusion
Addition of the MDQ to the EPDS improved the distinction of unipolar depression from bipolar depression at the level of screening in 50% of women with traditional MDQ scoring and by nearly 70% when the MDQ was scored without the impairment criterion.
This sample of perinatal women with BD was characterized by mild residual symptoms of depression independent of pharmacotherapy, which poses a risk for recurrence and impaired parenting. The treatment of childbearing women with BD deserves urgent clinical and research attention to improve psychiatric outcomes.
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