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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

Published online by Cambridge University Press:  16 April 2020

W.E. Severus ,
I.A. Lipkovich ,
R.W. Licht ,
A.H. Young ,
W. Greil ,
T. Ketter ,
W. Deberdt  and
M. Tohen
W.E. Severus*
Affiliation:
Department of Psychiatry, University of Munich, Nussbaumstrasse 7, 80336Munich, Germany
I.A. Lipkovich
Affiliation:
Eli Lilly and Company, Indianapolis, Indiana46285, USA
R.W. Licht
Affiliation:
Mood Disorders Unit, Aarhus University Psychiatric Hospital, Skovagervej 2, 8240, Risskov, Denmark
A.H. Young
Affiliation:
Institute of Mental Health, Department of Psychiatry, University of British Columbia, Suite 430, 5950 University Boulevard, Vancouver, BC V6T 1Z3, Canada
W. Greil
Affiliation:
Department of Psychiatry, University of Munich, Nussbaumstrasse 7, 80336Munich, Germany
T. Ketter
Affiliation:
Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 401, Quarry Road, Room 2124, Stanford, CA 94305-5723, USA
W. Deberdt
Affiliation:
Eli Lilly Benelux, Stoofstraat 52, 1000Brussels, Belgium
M. Tohen
Affiliation:
Division of Mood and Anxiety Disorders, University of Texas Health Science Center, 7703, Floyd Curl Drive, San Antonio, TX 78229, USA
*
*Corresponding author. Tel.: +0049 89 5160 5511; fax: +0049 89 5160 5809. E-mail address: Emanuel.Severus@med.uni-muenchen.de (W.E. Severus).
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Abstract

Purpose

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 (< 10 mg/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).

Conclusion

Lithium levels ≥ 0.6 mmol/L and olanzapine doses ≥ 10 mg/day may be necessary for optimal protection against manic/mixed or depressive episodes, respectively in patients with bipolar I disorder.

Keywords

LithiumOlanzapineMaintenance treatmentBipolar disorders
Type
Bipolar Disorder
Information
European Psychiatry , Volume 25 , Issue 8 , December 2010 , pp. 443 - 449
Copyright
Copyright © Elsevier Masson SAS 2010

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