A Double-Blind, Randomized, Placebo-Controlled Trial of Augmentation With Lamotrigine or Placebo in Patients Concomitantly Treated With Fluoxetine for Resistant Major Depressive Episodes
J Clin Psychiatry 2003;64(4):403-407
© Copyright 2015 Physicians Postgraduate Press, Inc.
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Background: Evidence of the antidepressant
efficacy of lamotrigine is increasing, although there are no
placebo-controlled trials of lamotrigine augmentation in
depression. The aim of this study was to assess if augmentation
with lamotrigine was superior to placebo in patients who were
receiving fluoxetine for resistant major depressive episodes.
Method: Twenty-three patients who had
experienced at least 1 major depressive episode that was
resistant to at least 1 prior trial of antidepressant therapy
were selected. These patients were treated with fluoxetine, 20
mg/day, and concomitantly randomly assigned to receive either
lamotrigine (N = 13) or placebo (N = 10) for 6 weeks. The dose of
lamotrigine was titrated upward from 25 mg/day to 100 mg/day.
Patients suffering from bipolar II disorder (N = 8) or from major
depressive disorder (N = 15) (DSM-IV criteria) were enrolled,
resulting in heterogeneity of the sample. The primary outcome
measure was Hamilton Rating Scale for Depression score. Data were
collected from 2000-2001.
Results: Lamotrigine was statistically superior
to placebo on the Clinical Global Impressions scale at endpoint,
both in absolute terms (mean ± SD Clinical Global
Impressions-Severity of Illness scores: lamotrigine, 2.15 ±
1.28; placebo, 3.40 ± 1.17; p = .0308) and using a responder
analysis, with response defined as a Clinical Global
Impressions-Improvement score of 2 or less (lamotrigine, 84.62%
[N = 11]; placebo, 30.00% [N = 3]; p = .013). The effect of
lamotrigine on Clinical Global Impressions scale scores was seen
in both major depressive disorder and bipolar II disorder.
Lamotrigine, however, failed to separate statistically from
placebo on the Hamilton Rating Scale for Depression and
Montgomery-Asberg Depression Rating Scale. This failure to
differentiate on a primary outcome measure is essentially a
negative study result. This result is most likely an artifact of
the small sample size used and the resultant limited power of the
Conclusion: The results of this trial add to the
literature suggesting potential efficacy of the antidepressant
profile of lamotrigine. In addition, this study points to a
possible role of lamotrigine as an augmentation agent in