Tricyclic antidepressants in pregnancy and puerperium

Several concerns have been raised regarding the reproductive safety of the antidepressants most frequently used in clinical practice, such as selective serotonin reuptake inhibitors (SSRIs).

This article aims to assess the risk/benefit ratio of the use of alternative pharmacological options, specifically tricyclic antidepressants (TCAs) in pregnancy and puerperium.

Although TCAs have been prescribed for several decades, their own teratogenic potential to cause structural defects remains undetermined. However, some signals seem to exist suggesting that prenatal clomipramine exposure may increase the risk of cardiac defects. Moreover, TCAs have been associated with the risk of prenatal antidepressant exposure syndrome. Among TCAs, clomipramine seems to be associated with more severe and prolonged neonatal symptoms. However, some findings of this syndrome reported with SSRI use, such as persistent pulmonary hypertension of the newborn, necrotizing enterocolitis and QT prolongation, have not been described after TCA exposure. Hence, current evidence suggests that, as a group, a preference of TCAs over SSRIs in early pregnancy is not justified. In contrast, there appears to be a small gain in safety if TCAs (with the exception of clomipramine) are used in late pregnancy. Among this class of antidepressants, nortriptyline seems to be safest medication for use during breastfeeding.