title: 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: 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.
  
  
  
  A retrospective observational study of patient data from 2 routine therapeutic drug monitoring services in Norway, linked to the Medical Birth Registry of Norway.
  
  
  
  Norway, October 1999 to December 2011.
  
  
  
  Dose-adjusted drug concentrations of lithium during pregnancy were compared with the women's own baseline (non-pregnant) values, using a linear mixed model.
  
  
  
  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).
  
  
  
  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.
authors.affiliation: Department of Clinical Pharmacology, St Olav University Hospital, Trondheim, Norway.
authors.forename: Andreas Austgulen
authors.identifier: 0000-0002-9198-5137
authors.initials: AA
authors.lastname: Westin
authors.affiliation: Center for Psychopharmacology, Diakonhjemmet Hospital, Oslo, Norway.
authors.forename: Malin
authors.initials: M
authors.lastname: Brekke
authors.affiliation: Center for Psychopharmacology, Diakonhjemmet Hospital, Oslo, Norway.|Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, Oslo, Norway.
authors.forename: Espen
authors.initials: E
authors.lastname: Molden
authors.affiliation: Department of Anaesthesiology and Intensive Care, St. Olav University Hospital, Trondheim, Norway.|Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Eirik
authors.initials: E
authors.lastname: Skogvoll
authors.affiliation: Department of Clinical Pharmacology, St Olav University Hospital, Trondheim, Norway.|Gildheim General Practice, Trondheim, Norway.
authors.forename: Marianne
authors.initials: M
authors.lastname: Aadal
authors.affiliation: Department of Clinical Pharmacology, St Olav University Hospital, Trondheim, Norway.|Department of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Olav
authors.initials: O
authors.lastname: Spigset
mesh_terms: D000328:Adult; D018692:Antimanic Agents / Q000008:administration & dosage / Q000097:blood*; D001714:Bipolar Disorder / Q000188:drug therapy*; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D016014:Linear Models; D018020:Lithium Compounds / Q000008:administration & dosage / Q000097:blood*; D009664:Norway; D049590:Postpartum Period; D011247:Pregnancy; D011263:Pregnancy Trimester, Third / Q000097:blood*; D012189:Retrospective Studies
chemical_list: D018692:Antimanic Agents; D018020:Lithium Compounds
keywords: CLINICAL PHARMACOLOGY; PSYCHIATRY