Returning to tricyclic antidepressants for depression during childbearing: clinical and dosing challenges

Abstract

Managing depression and anxiety during pregnancy and the postpartum period is challenging. Both pharmacological treatment and the lack thereof can pose threats to a fetus. SSRIs are the drugs of choice for use during pregnancy, but there is considerable evidence for the safety and efficacy of older antidepressants during pregnancy as well. This study highlights a single case of the use of the tricyclic nortriptyline during pregnancy and postpartum. The subject involved had an unexpectedly high ratio of serum level to drug dose during the postpartum period. We monitored the subject for a significantly greater portion of the postpartum period than has been done in previous studies, and explored medical and lifestyle changes that could account for the level-to-dose ratios we observed. Differences in smoking patterns, coupled with the patient’s status as a genetic poor metabolizer, were the most likely explanations.

Nortriptyline induces mitochondria and death receptor-mediated apoptosis in bladder cancer cells and inhibits bladder tumor growth in vivo

“…1B). Furthermore, NTP has a long history of use as an antidepressant without many detectable adverse effects (Menza et al, 2009;Osborne et al, 2014). Typically, NTP dosages are 25-75 mg/ day (Krymchantowski et al, 2011;Maizels and McCarberg, 2005;Yeragani et al, 2002), which correspond to plasma concentrations up to 10 μM (Yeragani et al, 2002).…”

Pharmacokinetics of Antidepressants in Pregnancy

“…The C/D ratios increased to 0.80 (ng/mL)/mg at 2 weeks postpartum and 1.02 (ng/mL)/mg at 4 weeks postpartum. Another case reported the C/D ratios in a 31‐year‐old woman treated with nortriptyline as 1.1 (μg/L)/mg at 11 weeks’ gestation, 1.21 (μg/L)/mg at 30 weeks’ gestation, 1.01 (μg/L)/mg at 36 weeks’ gestation, 2.45 (μg/L)/mg at 11 weeks postpartum, and 3.0 (μg/L)/mg at 33 weeks postpartum 61 …”

“…Although 24 studies included longitudinal data with maternal plasma trough concentrations during pregnancy (most in the third trimester), at delivery, and/or postpartum, there was often a large amount of missing data. [26][27][28]30,34,35,37,39,40,42,[45][46][47][48][49][51][52][53]55,56,[59][60][61]64 For example, a study of paroxetine reported data from 74 subjects total, but data were missing from 20 subjects in the first trimester, 8 in the second trimester, and 4 in the third trimester. 52 Another study of 55 subjects had 27 missing in the third trimester and 11 missing at delivery.…”

“…Another case reported the C/D ratios in a 31-year-old woman treated with nortriptyline as 1.1 (μg/L)/mg at 11 weeks' gestation, 1.21 (μg/L)/mg at 30 weeks' gestation, 1.01 (μg/L)/mg at 36 weeks' gestation, 2.45 (μg/L)/mg at 11 weeks postpartum, and 3.0 (μg/L)/mg at 33 weeks postpartum. 61 Although data are limited, nortriptyline concentrations during pregnancy appear to be lower than those before pregnancy or in the postpartum period. Six of the eight cases required a dose increase during pregnancy due to increased symptoms.…”

Reproductive Psychiatry: The Gap Between Clinical Need and Education

“…Epigenetic effects of antenatal stress and depression on fetal development ("fetal programming") are increasingly understood (19)(20)(21), as are the adverse long-term effects of postpartum depression on children (22)(23)(24)(25). In addition to these risks, there is also considerable literature on the potential risks of treatments to both mother and fetus (26)(27)(28), as well as a body of literature concerning drug disposition and pharmacokinetic changes in pregnancy and postpartum that may require dosage adjustments (29)(30)(31)(32). Clinicians who specialize in the field routinely use this new scientific information to craft individualized risk analyses for pregnant women who require treatment.…”