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.
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.
Severus
W E
WE
Department of Psychiatry, University of Munich, Nussbaumstrasse 7, Munich, Germany. Emanuel.Severus@med.uni-muenchen.de
Lipkovich
I A
IA
Licht
R W
RW
Young
A H
AH
Greil
W
W
Ketter
T
T
Deberdt
W
W
Tohen
M
M
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
D018692:Antimanic Agents; D001569:Benzodiazepines; D008094:Lithium; D000077152:Olanzapine