Table 1.
Pharmacokinetic data on antidepressants and observed changes in pregnancy
| Drug name | Primary active metabolite | Primary metabolic route | Non-pregnant elimination half-life | Dose linearity | Plasma protein binding | Excreted unchanged in urine | General conclusions |
|---|---|---|---|---|---|---|---|
| sertraline 76,77 | N-desmethylsertraline | CYP2B6,3A4, 2C19, 2D6, 2C9 | 22–36h | linear | 98% | minor | Weak evidence that sertraline exposure and parent/metabolite ratio decrease during pregnancy compared to postpartum, one study showed CYP2C19 genotype dependency |
| fluoxetine 78,79 | Norfluoxetine | CYP2D6, 2C9, 2C19 | 1–4d | nonlinear (>40mg) | 94.50% | <10% | Decreasing fluoxetine concentration throughout pregnancy and lower parent/metabolite ratio compared to postpartum |
| paroxetine 80 | CYP2D6, 3A4 | 21h | nonlinear | 93% | 2% | Decreasing paroxetine concentration throughout pregnancy, one study showed CYP2D6 genotype dependency | |
| citalopram 81,82 | N-desmethylcitalopram | CYP2C19, 3A4, 2D6 | 35h | linear | 80% | 10% | Weak evidence of decreasing citalopram concentrations throughout pregnancy and lower parent/metabolite ratio compared to postpartum |
| escitalopram 83,84 | N-desmethylescitalopram | CYP2C19, 3A4, 2D6 | 27–32h | linear | 56% | 8% | Inconsistent results |
| Fluvoxamine 85 | CYP2D6, 1A2 | 15–20h | nonlinear | 77% | 2% | Limited data showing decrease of fluvoxamine concentration during pregnancy and compared to postpartum | |
| venlafaxine 86,87 | O-desmethylvenlafaxine | CYP2D6, 2C19, 3A4, 2C9 | 5h | linear | 27% | 5% | Decrease of venlafaxine concentration and metabolic ratio during pregnancy |
| duloxetine 88 | CYP1A2, 2D6 | 10–12h | linear | >90% | <1% | Limited data | |
| trazodone 89 | m-Chlorophenylpiperazine (mCPP) | CYP3A4 | 7.1h | linear | 89–95% | <1% | Limited data |
| clomipramine 90,91 | N-desmethylclomipramine | CYP2D6, 2C19, 3A4, 1A2 | 19–37h | nonlinear | 97% | 0.80% | Weak evidence of decreasing clomipramine exposure and increasing parent/metabolite ratio during pregnancy |
| amitriptyline 92 | Nortriptyline | CYP2C19, 3A4, 2D6 | 25h | linear | 95% | 2% | Limited data showing decrease of amitriptyline concentration during pregnancy and compared to postpartum |
| nortriptyline 93,94 | 10-hydroxy-nortriptyline | CYP2D6 | 18–35h | linear | 93% | 2% | Decreasing nortriptyline concentrations throughout pregnancy |
| imipramine 95 | Desipramine | CYP1A2, 3A4, 2D6, 2C19 | 12h | linear | 60–96% | <5% | Limited data showing decrease of imipramine concentrations during pregnancy and compared to postpartum |
| mirtazapine 96,97 | N-desmethylmirtazapine | CYP2D6, 1A2, 3A4 | 20–40h | linear | 85% | 4% | Limited data showing decrease of mirtazapine concentrations during pregnancy and compared to postpartum |
| bupropion 98,99 | hydroxybupropion (OHBUP), threohydroxybupropion (TB) and erythrohydroxybupropion (EB) | CYP2B6, 2C19, 3A4 | 21h | linear | 84% | 0.50% | No significant change of bupropion exposure and apparent clearance; significantly higher EB/BUP ratio in second trimester, but not significant for OHBUP/BUP and TB/BUP |