title: How appropriate is therapeutic drug monitoring for lithium? Data from the Belgian external quality assessment scheme.
abstract: BACKGROUND
  Lithium remains a mainstay in the management of mood disorders. As with many psychotropic drugs, lithium treatment requires continuous observation for adverse effects and strict monitoring of serum concentrations. The present study aimed to assess the appropriateness of lithium assays used by Belgian laboratories, and to evaluate acceptability of their clinical interpretations.
  
  
  METHODS
  Nine in-house serum samples spiked with predetermined concentrations of lithium were distributed to 114 participants in the Belgian external quality assessment scheme. Laboratories were requested to report the assay technique, lithium measurements and interpretations with regard to measured concentrations. Inter/intramethod imprecision and bias were reported and acceptability of clinical interpretations was assessed. The intramethod variability was evaluated by selecting methods used by 6 laboratories or more. Flame photometry (IL 943) was considered as the reference method.
  
  
  RESULTS
  Laboratories returned assay results using colorimetry (69.3%), ion selective electrode (15.8%), flame photometry (8.8%), atomic absorption spectroscopy (5.2%) or mass spectrometry (0.9%). Lithium concentrations were systematically higher when measured with the Vitros assay (median bias: 4.0%), and were associated with consecutive biased interpretations. In contrast, the Thermo Scientific Infinity assay showed a significant negative bias (median bias: 9.4%). 36.0% of laboratories reported numerical values below their manufacturer cut-off for the blank sample; 16.6% of these laboratories detected residual lithium concentrations.
  
  
  CONCLUSIONS
  The present study revealed assay-related differences in lithium measurements and their interpretations. Overall, there appeared to be a need to continue EQA of therapeutic drug monitoring for lithium in Belgium.
authors.affiliation: Quality of Medical Laboratories, Scientific Institute of Public Health, Belgium; Laboratory of Toxicology and Therapeutic Drug Monitoring, University Hospital St Luc, Belgium.
authors.forename: I K
authors.initials: IK
authors.lastname: Delattre
authors.affiliation: Quality of Medical Laboratories, Scientific Institute of Public Health, Belgium. Electronic address: pvandewalle@wiv-isp.be.
authors.forename: P
authors.initials: P
authors.lastname: Van de Walle
authors.affiliation: Quality of Medical Laboratories, Scientific Institute of Public Health, Belgium.
authors.forename: C
authors.initials: C
authors.lastname: Van Campenhout
authors.affiliation: Laboratory of Toxicology and Therapeutic Drug Monitoring, Ziekenhuis Netwerk Antwerpen campus Stuivenberg, Belgium.
authors.forename: H
authors.initials: H
authors.lastname: Neels
authors.affiliation: Laboratory of Clinical Biology/Toxicology, Ghent University Hospital, Belgium.
authors.forename: A G
authors.initials: AG
authors.lastname: Verstraete
authors.affiliation: Laboratory of Toxicology and Therapeutic Drug Monitoring, University Hospital St Luc, Belgium.
authors.forename: P
authors.initials: P
authors.lastname: Wallemacq
mesh_terms: D014150:Antipsychotic Agents / Q000097:blood*; D001530:Belgium; D019411:Clinical Laboratory Techniques; D003124:Colorimetry / Q000592:standards; D016903:Drug Monitoring / Q000592:standards*; D006801:Humans; D007753:Laboratories; D008094:Lithium / Q000097:blood*; D013058:Mass Spectrometry / Q000592:standards; D010783:Photometry / Q000592:standards; D015203:Reproducibility of Results
chemical_list: D014150:Antipsychotic Agents; D008094:Lithium
keywords: Bipolar disorder; External quality assessment; Lithium; Therapeutic drug monitoring