Risk of Fetal Exposure to Tricyclic Antidepressants

Abstract

Objectives: (1) To review the literature on the risk of fetal exposure to tricyclic antidepressants (TCAs). (2) To estimate the frequency of TCA exposure in pregnant women in the Canadian province of Saskatchewan.Methods: MEDLINE was searched for English-language papers published from 1953 to 2003, using the key words “tricyclic antidepressants (TCAs),” “amitriptyline,” “amoxapine,” “clomipramine,” “desipramine,” “doxepin,” “imipramine,” “lofepramine,” “maprotiline,” “nortriptyline,” “protriptyline,” and “trimipramine.” The search was restricted to human studies. To estimate potential exposure to TCAs during pregnancy, data from the outpatient prescription drug database of Saskatchewan, Canada, were analyzed.Results: The number of women of reproductive age (16 to 44 years) with at least I prescription of genotoxic TCAs was 3501 in 1977,2959 in 1991, and 1330 in 1999. Corresponding figures for non-genotoxic TCAs were 3403, 4200, and 5493, respectively. Based on these figures, the rates of prescriptions given to women of reproductive age in any particular calendar year were 1.30% (95% confidence interval [CI], 1.25%–1.35%) for genotoxic TCAs, and 2.32% (95% CI, 2.25%–2.39%) for non-genotoxic TCAs.Conclusions: Prescription of TCAs to women of reproductive age is quite frequent, and there has been no apparent decline in prescriptions in recent years. The frequent prescription of potentially toxic TCAs to pregnant women may be due to increases in unplanned pregnancies in industrial countries, lack of adequate scientific evidence on the adverse effects of TCAs, and conflicting needs to treat maternal diseases and to protect fetuses. Consultation with specialists experienced in treating depression may be helpful when treating pregnant women with TCAs. Large-scale epidemiologic studies to assess the potential adverse effects of TCAs use in pregnancy on a broad spectrum of fetal and infant outcomes are needed. The findings from such studies will have direct implication on the use of TCAs in the clinical treatment of depression in pregnancy.