A Placebo-Controlled 18-Month Trial of Lamotrigine and Lithium Maintenance Treatment in Recently Depressed Patients With Bipolar I Disorder
J Clin Psychiatry 2003;64(9):1013-1024
© Copyright 2014 Physicians Postgraduate Press, Inc.
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Background: The anticonvulsant lamotrigine was
previously shown to be effective for bipolar depression. This
study assessed the efficacy and tolerability of lamotrigine and
lithium compared with placebo for the prevention of mood episodes
in bipolar disorder.
Method: During an 8- to 16-week open-label
phase, lamotrigine (titrated to 200 mg/day) was added to current
therapy for currently or recently depressed DSM-IV-defined
bipolar I outpatients (N = 966) and concomitant drugs were
gradually withdrawn. Patients stabilized on open-label treatment
(N = 463) were then randomly assigned to lamotrigine (50, 200, or
400 mg/day; N = 221), lithium (0.8-1.1 mEq/L; N = 121), or
placebo (N = 121) monotherapy for up to 18 months. The primary
outcome measure was time from randomization to intervention
(addition of pharmacotherapy) for any mood episode (depressive,
manic, hypomanic, or mixed). Data were gathered from September
1997 to August 2001.
Results: Time to intervention for any
mood episode was statistically superior (p = .029) for both
lamotrigine and lithium compared with placebo-median survival
times were 200, 170, and 93 days, respectively. Intervention for
depression was more frequent than for mania by a factor of nearly
3:1. Lamotrigine was statistically superior to placebo at
prolonging the time to intervention for a depressive episode (p =
.047). The proportions of patients who were intervention-free for
depression at 1 year were lamotrigine 57%, lithium 46%, and
placebo 45%. Lithium was statistically superior to placebo at
prolonging the time to intervention for a manic or hypomanic
episode (p = .026). The proportions of patients who were
intervention-free for mania at 1 year were lamotrigine 77%,
lithium 86%, and placebo 72%. Headache was the most frequent
adverse event for all 3 treatment groups.
Conclusion: Lamotrigine and lithium were
superior to placebo for the prevention of mood episodes in
bipolar I patients, with lamotrigine predominantly effective
against depression and lithium predominantly effective against