Changes in drug disposition of lithium during pregnancy: A retrospective observational study of patient data from two routine therapeutic drug monitoring services in Norway

Abstract

Objectives Pregnancy may cause changes in drug disposition, dose requirements and clinical response. For lithium, changes in disposition during pregnancy have so far been explored in a single-dose study on 4 participants only. The aim of this study was to determine the effect of pregnancy on serum levels of lithium in a larger patient material in a naturalistic setting.

Design A retrospective observational study of patient data from 2 routine therapeutic drug monitoring services in Norway, linked to the Medical Birth Registry of Norway.

Setting Norway, October 1999 to December 2011.

Measurements Dose-adjusted drug concentrations of lithium during pregnancy were compared with the women's own baseline (non-pregnant) values, using a linear mixed model.

Results Overall, coupling 196 726 serum concentration measurements from 54 393 women to the national birth registry identified 25 serum lithium concentration analyses obtained from a total of 14 pregnancies in 13 women, and 63 baseline analyses from the same women. Dose-adjusted serum concentrations in the third trimester were significantly lower than baseline (−34%; CI −44% to −23%, p<0.001).

Conclusions Pregnancy causes a clinically relevant decline in maternal lithium serum concentrations. In order to maintain stable lithium concentrations during the third trimester of pregnancy, doses generally need to be increased by 50%. Individual variability in decline implies that lithium levels should be even more closely monitored throughout pregnancy and in the puerperium than in non-pregnant women to ensure adequate dosing.