title: Is the polarity of relapse/recurrence in bipolar-I disorder patients related to serum lithium levels? Results from an empirical study.
abstract: BACKGROUND
  Preliminary evidence suggests that the polarity of relapse/recurrence (depressive vs. hypomanic/manic/mixed) in bipolar patients on lithium might be related to serum lithium levels.
  
  
  METHODS
  Polarity of episodes in 64 bipolar-I patients on lithium monotherapy during a prospective 18-month maintenance trial was predicted from (a) intra-individual oscillations of lithium levels over time and from (b) absolute lithium levels preceding relapse/recurrence.
  
  
  RESULTS
  On an individual basis, depressive (vs. hypomanic/manic/mixed) episodes were mostly preceded by lithium levels above the individual means (p<0.001). Relapse/recurrence occurring at lithium levels above the overall mean serum level of 0.66 mmol/l was depressive (not hypomanic/manic/mixed) in most cases (odds-ratio=3.86, p=0.032). Lithium levels before depressive episodes were numerically higher than before hypomanic/manic/mixed episodes (0.769+/-0.242 vs. 0.675+/-0.262 mmol/l, p=0.13). Cox-regression including current lithium levels as time-dependent predictor essentially confirmed these results.
  
  
  CONCLUSIONS
  As patients were not randomized to specific lithium levels, potential confounders could not be completely ruled out. Furthermore, a closer than monthly assessment of both lithium levels and psychopathology would have been desirable to better understand the interplay between lithium levels and new mood episodes.
  
  
  CONCLUSIONS
  The results indicate that within the currently accepted therapeutic range (0.4-1.1 mmol/l), the relative risk for depressive vs. hypomanic/manic/mixed relapses/recurrences may be associated with higher lithium levels. Therefore, lithium levels at the lower range of the therapeutic spectrum may be sufficient for the optimal prevention of depressive episodes whereas higher lithium levels within this range may be needed for optimal protection against manic/mixed episodes.
authors.affiliation: Department of Psychiatry, University of Munich, Munich, Germany.
authors.forename: W E
authors.initials: WE
authors.lastname: Severus
authors.forename: N
authors.initials: N
authors.lastname: Kleindienst
authors.forename: G
authors.initials: G
authors.lastname: Evoniuk
authors.forename: C
authors.initials: C
authors.lastname: Bowden
authors.forename: H J
authors.initials: HJ
authors.lastname: Möller
authors.forename: M
authors.initials: M
authors.lastname: Bohus
authors.forename: S
authors.initials: S
authors.lastname: Frangou
authors.forename: W
authors.initials: W
authors.lastname: Greil
authors.forename: J R
authors.initials: JR
authors.lastname: Calabrese
mesh_terms: D000328:Adult; D018692:Antimanic Agents / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000097:blood / Q000188:drug therapy* / Q000517:prevention & control; D001774:Blood Chemical Analysis; D003863:Depression / Q000097:blood / Q000188:drug therapy* / Q000517:prevention & control; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008094:Lithium / Q000097:blood*; D018020:Lithium Compounds / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011446:Prospective Studies; D011569:Psychiatric Status Rating Scales; D012306:Risk; D055502:Secondary Prevention; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D018692:Antimanic Agents; D018020:Lithium Compounds; D008094:Lithium