For decades,
lithium and
anticonvulsants have been widely used in the treatment of
bipolar disorder. Their efficacy in the treatment of
mania is recognized. These drugs have been initially evaluated in old and methodologically heterogeneous studies. Their efficacy in
bipolar depression has not always been confirmed in more recent and methodologically more reliable studies. Thus,
lithium's efficacy as monotherapy was challenged by the study of Young (2008) that showed a lack of efficacy compared with placebo in the treatment of
bipolar depression. In two recent meta-analyses,
valproate has shown a modest efficacy in the treatment of
bipolar depression. As for
lithium,
valproate appeared to have a larger
antimanic effect for acute phase and prophylaxis of
bipolar disorder. In contrast,
lamotrigine is more effective on the depressive pole of
bipolar disorder with better evidence for the prevention of depressive recurrences. The guidelines include these recent studies and recommend
lamotrigine as a first-line treatment of
bipolar depression and for maintenance treatment. Because of more discordant data concerning
lithium and
valproate, these two drugs are placed either as first or as second line treatment of
bipolar depression. The different safety/efficacy ratios of mood stabilizers underlie the complementarity and the importance of combination between them, or with some second-generation
antipsychotics, in the treatment of patients with
bipolar disorder.