Incidence and Time Course of Subsyndromal Symptoms in Patients With Bipolar I Disorder: An Evaluation of 2 Placebo-Controlled Maintenance Trials
J Clin Psychiatry 2006;67(11):1721-1728
© Copyright 2015 Physicians Postgraduate Press, Inc.
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Background: Subsyndromal symptoms in
bipolar disorder can cause significant functional
impairment and are associated with relapse.
Method: In this post hoc analysis from 2
randomized, double-blind, 18-month, placebo-controlled maintenance trials for bipolar I
disorder (both trials were conducted between August
1997 and August 2001 and used DSM-IV criteria),
the incidence, time course, and impact of pharmacotherapy on subsyndromal symptoms were
Results: Subsyndromal symptoms occurred
in approximately 25% of all visits. Compared with placebo (54.8%), a significantly higher mean
percentage of visits in remission were observed
with lamotrigine treatment (63.0%, p = .020) but
not with lithium treatment (60.0%, p = .165). The
median time to onset of subsyndromal symptoms for lamotrigine (N = 223), lithium (N = 164), and
placebo (N = 188) was 15, 15, and 9 days, respectively. Compared with placebo, both
lamotrigine and lithium significantly delayed the time
from randomization to onset of subsyndromal
symptoms (p = .046, lamotrigine vs. placebo; p = .033,
lithium vs. placebo; p = .763, lamotrigine vs.
lithium) and the time from onset of subsyndromal
symptoms to subsequent mood episode (p = .037,
lamotrigine vs. placebo; p = .023, lithium vs. placebo;
p = .845, lamotrigine vs. lithium). Agreement between the polarities of the first-observed
subsyndromal symptom and subsequent intervention
for mood episode was statistically significant (p
Conclusion: Subsyndromal symptoms are
common during maintenance treatment and appear to be associated with relapse into an episode of
the same polarity. Both lithium and lamotrigine delayed the onset of subsyndromal symptoms and
the time from onset of subsyndromal symptoms to subsequent relapse. Further study to
assess whether treatment intervention can minimize
subsyndromal symptoms or prevent relapse is encouraged.