title: The impact of environmental temperature on lithium serum levels.
abstract: OBJECTIVE
  Three studies have reported a seasonal variation in lithium serum levels, with higher levels during summer. Our objective was to investigate the impact of actual environmental temperature on lithium serum levels.
  
  
  METHODS
  A retrospective study was conducted using available records of lithium serum levels for the period between January 1995 and July 2004, obtained from three large teaching hospitals in The Netherlands. Lithium serum levels were linked to season and average daily temperature data obtained from the Royal Netherlands Meteorological Institute. An analysis was performed on all lithium serum levels not accounting for the intra-individual dependency of lithium serum levels. The association between season, temperature and both absolute lithium serum level and the frequency of potentially toxic serum levels was investigated. A mixed model analysis, accounting for intra-individual dependency of lithium serum levels, was performed.
  
  
  RESULTS
  A total of 41,102 lithium serum levels (3,054 patients) were included. A significant difference in mean lithium serum levels across seasons (p < 0.001) and temperature categories (p = 0.001) was found, peaking in summer [0.761 mmol/L, +/- standard error of the mean (SEM) 0.002] and at temperatures of 15-20 degrees C [0.762 mmol/L (+/- SEM 0.005)], and at a minimum in winter [0.748 mmol/L (+/- SEM 0.002)] and at <0 degrees C [0.741 mmol/L (+/- SEM 0.005)]. The relative frequency of potentially toxic serum levels significantly differed between seasons (p = 0.023, highest in winter), but not between temperature categories (p = 0.481). A significant positive association for intra-individual lithium serum level and season (p < 0.001) and temperature (p < 0.001) was established.
  
  
  CONCLUSIONS
  Season and environmental temperature have a statistically significant but therapeutically irrelevant effect on lithium serum levels.
authors.affiliation: Department of Pharmacoepidemiology and Pharmacotherapy, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
authors.forename: Ingeborg
authors.initials: I
authors.lastname: Wilting
authors.forename: Sandra
authors.initials: S
authors.lastname: Fase
authors.forename: Edwin P
authors.initials: EP
authors.lastname: Martens
authors.forename: Eibert R
authors.initials: ER
authors.lastname: Heerdink
authors.forename: Willem A
authors.initials: WA
authors.lastname: Nolen
authors.forename: Antoine C  G
authors.initials: AC
authors.lastname: Egberts
mesh_terms: D001714:Bipolar Disorder / Q000097:blood* / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D001831:Body Temperature; D001833:Body Temperature Regulation; D014644:Genetic Variation; D006801:Humans; D018020:Lithium Compounds / Q000493:pharmacokinetics* / Q000627:therapeutic use; D012189:Retrospective Studies; D012621:Seasons; D013696:Temperature
chemical_list: D018020:Lithium Compounds