Changes in drug disposition of lithium during pregnancy: A retrospective observational study of patient data from two routine therapeutic drug monitoring services in Norway
Journal article, Peer reviewed
Published version
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http://hdl.handle.net/11250/2480321Utgivelsesdato
2017Metadata
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Originalversjon
10.1136/bmjopen-2016-015738Sammendrag
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.