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Changes in drug disposition of lithium during pregnancy: a retrospective observational study of patient data from two routine therapeutic drug monitoring services in Norway
  1. Andreas Austgulen Westin1,
  2. Malin Brekke2,
  3. Espen Molden2,3,
  4. Eirik Skogvoll4,5,
  5. Marianne Aadal1,6,
  6. Olav Spigset1,7
  1. 1Department of Clinical Pharmacology, St Olav University Hospital, Trondheim, Norway
  2. 2Center for Psychopharmacology, Diakonhjemmet Hospital, Oslo, Norway
  3. 3Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, Oslo, Norway
  4. 4Department of Anaesthesiology and Intensive Care, St. Olav University Hospital, Trondheim, Norway
  5. 5Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway
  6. 6Gildheim General Practice, Trondheim, Norway
  7. 7Department of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology, Trondheim, Norway
  1. Correspondence to Dr Andreas Austgulen Westin; andreas.westin{at}stolav.no

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.

  • PSYCHIATRY
  • CLINICAL PHARMACOLOGY

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

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Footnotes

  • Twitter Follow Andreas Westin @Andreas_Westin

  • Contributors AAW, EM and OS designed the study protocol, and participated in the coordination and management of the study. AAW, MB and MA performed the data acquisition from the therapeutic drug monitoring databases. AAW and ES performed the statistical analysis, and all authors participated in the interpretation and discussion of the results. AAW wrote the first manuscript draft, and all authors revised it critically. All authors read and approved the final manuscript.

  • Funding This research received no specific grant from any funding agency in the public, commercial or non-for-profit sectors.

  • Competing interests None declared.

  • Ethics approval This study was approved by the Regional Committee for Medical and Health Research Ethics, the Norwegian Centre for Research Data (Data Protection Official), the Norwegian Directorate of Health, and the Medical Birth Registry of Norway (MBRN). The need for informed consent was waived by the Regional Committee for Medical and Health Research Ethics (Ref. No. 08/8544–2) and the Norwegian Directorate of Health (Ref. No. 08/10184), according to Norwegian legislation.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement No additional data are available.

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