The Use of Antidepressants in Bipolar Disorder
J Clin Psychiatry 2008;69(8):1307-1318
© Copyright 2015 Physicians Postgraduate Press, Inc.
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Background: Whether or not to use
antidepressants in patients with bipolar disorder is a matter
of debate. Antidepressant treatment of bipolar
depression has been associated with manic switch and
cycle acceleration. Furthermore, recent studies have
argued against the efficacy of antidepressants in the
treatment of bipolar depression. Nevertheless, many
clinicians continue to employ antidepressants,
especially in the management of severe depression that
is unresponsive to mood stabilizers alone.
Objective: Because of the unclear
risk-to-benefit ratio of antidepressants in bipolar disorder, we
have performed an updated review of the relevant
literature. In this article we examine (1) all
randomized controlled trials (RCTs) evaluating the use of
antidepressants in the treatment of acute bipolar
depression and assessing the risk of
antidepressant-induced manic switch and (2) non-RCT trials that
evaluate the impact of antidepressant discontinuation
after acute antidepressant response.
Data Sources: A MEDLINE search of
journals, covering the period from January 1966 to July
2007 and supplemented by bibliographic
cross-referencing, was performed to identify the relevant
studies. The keywords used were
antidepressant, bipolar depression,
bipolar disorder, switch, manic
switch, antidepressant-induced mania,
predictors, and antidepressant
discontinuation. Criteria used to select studies included (1) English language and (2)
studies published in peer-reviewed journals.
Data Synthesis: Randomized, double-blind,
placebo-controlled studies have demonstrated that
antidepressants exert some efficacy in the treatment
of bipolar depression in some populations of
patients. Moreover, the risk of manic switch, although
not totally countered, appears to be strongly
reduced when antidepressants are given in combination
with a mood stabilizer and when new-generation
antidepressants are preferred over old tricyclic
antidepressants. Finally, some studies have proven that the
continuous use of antidepressants after the remission
of a major depressive episode helps to prevent
further depressive relapses without causing a
significant increase in manic relapses.
Conclusion: Clearly, there is a place for
antidepressants in bipolar disorder; however, it is
important to be cautious and evaluate their use on a
case-by-case basis. Looking at specific depressive
symptoms might help physicians in making the choice
of whether to prescribe or not prescribe antidepressants.