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

BMJ Open. 2017 Mar 1;7(3):e015738. doi: 10.1136/bmjopen-2016-015738.


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.


Publication types

  • Multicenter Study
  • Observational Study

MeSH terms

  • Adult
  • Antimanic Agents / administration & dosage
  • Antimanic Agents / blood*
  • Bipolar Disorder / drug therapy*
  • Drug Monitoring*
  • Female
  • Humans
  • Linear Models
  • Lithium Compounds / administration & dosage
  • Lithium Compounds / blood*
  • Norway
  • Postpartum Period
  • Pregnancy
  • Pregnancy Trimester, Third / blood*
  • Retrospective Studies


  • Antimanic Agents
  • Lithium Compounds