title: In search of optimal lithium levels and olanzapine doses in the long-term treatment of bipolar I disorder. A post-hoc analysis of the maintenance study by Tohen et al. 2005.
abstract: OBJECTIVE
  The aim of this study was to investigate whether lower lithium levels (LoLi) or olanzapine doses (LoOL) are risk factors for future mood episodes in patients with bipolar I disorder.
  
  
  METHODS
  A post-hoc analysis of the olanzapine-lithium-maintenance study [31] was performed using proportional hazards Cox regression models and marginal structural models (MSMs), adjusting for non-random assignments of dose during treatment.
  
  
  RESULTS
  The LoLi group (<0.6 mmol/L) had a significantly increased risk of manic/mixed (hazard ratio [HR]=1.96, p=0.042), but not depressive (HR=2.11, p=0.272) episodes, compared to the combined medium (0.6-0.79 mmol/L) and high lithium level (≥0.8 mmol/L) groups. There was no significant difference in risk between the two higher lithium level groups (0.6-0.79 mmol/L; ≥0.8 mmol/L) for new manic/mixed (HR=0.96, p=0.893) or depressive (HR=0.95, p=0.922) episodes. The LoOL group (<10mg/day) showed a significantly increased risk of depressive (HR=2.24, p=0.025) episodes compared to the higher olanzapine (HiOL) dose group (HiOL: 10-20 mg/day), while there was no statistically significant difference in risk for manic/mixed episodes between the two groups (HR=0.94, p=0.895).
  
  
  CONCLUSIONS
  Lithium levels≥0.6 mmol/L and olanzapine doses≥10mg/day may be necessary for optimal protection against manic/mixed or depressive episodes, respectively in patients with bipolar I disorder.
authors.affiliation: Department of Psychiatry, University of Munich, Nussbaumstrasse 7, Munich, Germany. Emanuel.Severus@med.uni-muenchen.de
authors.forename: W E
authors.initials: WE
authors.lastname: Severus
authors.forename: I A
authors.initials: IA
authors.lastname: Lipkovich
authors.forename: R W
authors.initials: RW
authors.lastname: Licht
authors.forename: A H
authors.initials: AH
authors.lastname: Young
authors.forename: W
authors.initials: W
authors.lastname: Greil
authors.forename: T
authors.initials: T
authors.lastname: Ketter
authors.forename: W
authors.initials: W
authors.lastname: Deberdt
authors.forename: M
authors.initials: M
authors.lastname: Tohen
mesh_terms: D018692:Antimanic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D001569:Benzodiazepines / Q000008:administration & dosage* / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000188:drug therapy*; D003866:Depressive Disorder / Q000209:etiology; D005260:Female; D006801:Humans; D008094:Lithium / Q000008:administration & dosage* / Q000097:blood* / Q000627:therapeutic use; D016015:Logistic Models; D008297:Male; D000077152:Olanzapine; D016016:Proportional Hazards Models; D012008:Recurrence; D012307:Risk Factors; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D018692:Antimanic Agents; D001569:Benzodiazepines; D008094:Lithium; D000077152:Olanzapine