Concentrations of venlafaxine and its main metabolite O-desmethylvenlafaxine during pregnancy

What is known and objective Depression during pregnancy is common and includes risks for mother and child. Pharmacokinetics of venlafaxine may be changed during pregnancy. This study aimed to describe changes in metabolic ratios and concentrations of venlafaxine and its main metabolite O-desmethylvenlafaxine during and after pregnancy. Methods To study this, we used data from our study of compliance to Antidepressants During Pregnancy (the ADAP study) to investigate the course of venlafaxine and O-desmethylvenlafaxine concentrations during pregnancy and in the period post-partum. Results and discussion We found that the venlafaxine concentration significantly changed during pregnancy when compared to the post-partum period (P=0 center dot 028). The median concentration of venlafaxine in the first trimester was 98 center dot 9% (54 center dot 2-292 center dot 0%), the second 100 center dot 0% (46 center dot 5-264 center dot 0%) and the third trimester 87 center dot 0% (61 center dot 5-217 center dot 2%). We did not found differences in O-desmethylvenlafaxine concentrations in the different trimesters of pregnancy compared with the post-partum period, P=0 center dot 565. Also the ratio of O-desmethylvenlafaxine/venlafaxine concentrations increased significantly from 76 center dot 9% (range 32 center dot 8-142 center dot 0%) in the first trimester to 196 center dot 7% (range 83 center dot 3-427 center dot 6%) in the third trimester compared with the post-partum period, P=0 center dot 004. Further, three of seven patients had concentrations below the therapeutic reference range (100-400g/L) in any period of pregnancy, whereas no one had subtherapeutic concentrations in the post-partum period. What is new and conclusion Venlafaxine concentrations decreases during pregnancy, and the ratio of the concentrations of O-desmethylvenlafaxine/venlafaxine increases during pregnancy. Pregnant women using venlafaxine are at risk for subtherapeutic concentrations, therefore routine monitoring of concentrations venlafaxine and O-desmethylvenlafaxine is recommendable during pregnancy.