The current study suggests that within a similarly aged population of women with no lifetime history of depression, those who enter the menopausal transition earlier have a significant risk for first onset of depression. Further studies are needed to determine more definitively whether other factors, such as the presence of vasomotor symptoms, use of hormone therapy, and the occurrence of adverse life events, independently modify this risk. Physical symptoms associated with the menopausal transition and mood changes seen during this period may affect many women as they age and may lead to a significant burden of illness.
Pregnancy is not "protective" with respect to risk of relapse of major depression. Women with histories of depression who are euthymic in the context of ongoing antidepressant therapy should be aware of the association of depressive relapse during pregnancy with antidepressant discontinuation.
Background
There is controversy regarding whether the use of selective serotonin reuptake inhibitors (SSRIs) and other antidepressants in pregnancy is associated with increased risks for congenital cardiac defects. In particular, concerns exist about a possible association between paroxetine and right ventricular outflow tract obstruction (RVOTO), and between sertraline and ventricular septal defects (VSD).
Methods
We performed a cohort study nested in the 2000–2007 nationwide Medicaid Analytic eXtract. The study included 949,504 pregnant women enrolled in Medicaid from three months before conception through one month post delivery, and their live-born infants. We compared the risk of major cardiac defects in women with antidepressant medication use during the first trimester versus no use, restricting the cohort to women with depression and using propensity score adjustment to control for depression severity and other potential confounders.
Results
64,389 women (6.8%) used antidepressants during the first trimester. Overall, 6,403 infants not exposed to antidepressants were born with a cardiac defect (72.3 per 10,000), compared with 580 infants exposed (90.1 per 10,000). Associations between antidepressant use and cardiac defects were attenuated with increasing levels of adjustment for confounding. For SSRIs, relative risks for any cardiac defect were 1.25 (95%CI, 1.13–1.38) unadjusted, 1.12 (1.00–1.26) depression-restricted, and 1.06 (0.93–1.22) depression-restricted and fully-adjusted. We found no significant associations between the use of paroxetine and RVOTO (1.07, 0.59–1.93), or the use of sertraline and VSD (1.04, 0.76–1.41).
Conclusions
Results of this large population-based cohort study suggest no substantial increased risk of cardiac malformations attributable to SSRIs.
Discontinuation of mood stabilizer, particularly abruptly, during pregnancy carries a high risk for new morbidity in women with bipolar disorder, especially for early depressive and dysphoric states. However, this risk is reduced markedly by continued mood stabilizer treatment. Treatment planning for pregnant women with bipolar disorder should consider not only the relative risks of fetal exposure to mood stabilizers but also the high risk of recurrence and morbidity associated with stopping maintenance mood stabilizer treatment.
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