USE OF TRICYCLIC ANTIDEPRESSANTS IN PREGNANCY

Tricyclic antidepressants (TCAs) block the re-uptake of both serotonin and noradrenaline and are used in the management of depression, anxiety disorders and neuropathic pain. Currently available TCAs include amitriptyline, clomipramine, dosulepin, doxepin, imipramine, lofepramine, nortriptyline and trimipramine. 

The available data provides no strong evidence of an association between maternal use of TCAs as a class during pregnancy and an increased risk of congenital malformation overall, or of any specific malformations. There is limited or no information on use of specific TCAs, therefore an increased risk of malformations cannot be ruled out. A possible association between in utero clomipramine exposure and cardiac malformations has been suggested but remains to be confirmed. Other findings are conflicting; however possible associations with spontaneous abortion, preterm delivery, preeclampsia, and autism spectrum disorder have been identified.

An increased incidence of neonatal complications has been reported in the offspring of women with psychiatric illnesses; however the relative contributions of the underlying maternal condition and specific drug treatments have not been clearly defined. Use of TCAs throughout pregnancy or near delivery may be associated with withdrawal symptoms in the neonate and/or poor neonatal adaptation syndrome (PNAS). These symptoms are likely to be more severe in infants exposed in utero to more than one CNS acting drug.

It is important to ensure that maternal mental health disorders are treated appropriately during pregnancy. Where a patient is stabilised on a TCA, either prior to conception or during pregnancy, the risk of discontinuing or changing medication, or reducing the dose, should be carefully weighed against the risk of relapse of the maternal condition.

The currently available data do not support the need for any additional fetal monitoring following in utero exposure to TCAs; however data on individual TCAs is limited and the need for additional monitoring should therefore be determined on a case-by-case basis. Other risk factors may also be present in individual cases which may independently increase the risk of adverse pregnancy outcome. Clinicians are reminded of the importance of consideration of such factors when performing case-specific risk assessments.

There is a separate UKTIS monograph on Use of amitriptyline in pregnancy.