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The association of the effect of lithium in the maintenance treatment of bipolar disorder with lithium plasma levels: a post hoc analysis of a double-blind study comparing switching to lithium or placebo in patients who responded to quetiapine (Trial 144)

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  • Clinical trial registration information: Quetiapine Fumarate Bipolar Maintenance Monotherapy (SPaRCLe); D1447C00144; http://clinicaltrials.gov/ct2/show/NCT00314184?cntry1=SA%3ACO&rank=29.
    Portions of these data were presented in poster format at the Eighth International Conference on Bipolar Disorders, June 25–27, 2009, Pittsburgh, PA, USA and at the 22nd ECNP Congress, September 12–16, 2009, Istanbul, Turkey.

Corresponding author:
Willem A Nolen, M.D., Ph.D.
Department of Psychiatry
University Medical Center Groningen
University of Groningen
Hanzeplein 1
Groningen 9713GZ
The Netherlands
Fax: +31-503619132
E-mail: w.a.nolen@umcg.nl

Abstract

Nolen WA, Weisler RH. The association of the effect of lithium in the maintenance treatment of bipolar disorder with lithium plasma levels: a post hoc analysis of a double-blind study comparing switching to lithium or placebo in patients who responded to quetiapine (Trial 144).
Bipolar Disord 2012: 00: 000–000. © 2012 John Wiley & Sons A/S.Published by Blackwell Publishing Ltd.

Objectives:  There is no robust proof that the efficacy of lithium in the prevention of manic and depressive episodes in bipolar disorder depends on its plasma level. This analysis aimed to compare the effect of lithium within the presumed therapeutic range of 0.6–1.2 mEq/L and below 0.6 mEq/L with that of placebo.

Methods:  We carried out a post hoc analysis of a double-blind trial in which patients aged ≥18 years with bipolar I disorder (DSM-IV) who had achieved stabilization from a manic, depressive, or mixed episode during open-label treatment with quetiapine were randomized to continue quetiapine or to switch to lithium or placebo for up to 104 weeks. Of patients randomized to lithium, 201 obtained median lithium levels between 0.6 and 1.2 mEq/L, and 137 obtained median lithium levels <0.6 mEq/L. Their outcomes were compared with those of patients receiving placebo (n = 404). The primary outcome was time to recurrence of any mood event; additional outcomes included time to recurrence of a manic or depressive event.

Results:  Times to recurrence of any mood event as well as a manic or depressive event were significantly longer for the lithium 0.6–1.2 mEq/L group versus placebo and versus lithium <0.6 mEq/L, with no differences between lithium <0.6 mEq/L and placebo.

Conclusions:  The results support and expand previous findings that lithium should be dosed high enough to achieve plasma levels ≥0.6 mEq/L in order to achieve an effect in the prevention of both manic and depressive recurrences of bipolar I disorder. A major limitation is that the composition of the two lithium groups was not based on randomization.

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