None of the SSRIs are specifically indicated or promoted for use in the treatment of patients with bipolar depression. In the absence of such promotional claims, the controlled evidence supporting the use of an antidepressant in combination with a mood stabilizer for the treatment of bipolar depression is summarized below. 

Published evidence

Despite apparent widespread use, there are limited controlled data supporting the use of antidepressants with or without concomitant mood stabilizers. A placebo-controlled trial tested fluoxetine in combination with olanzapine (see olanzapine section). One small, randomized trial compared the efficacy of venlafaxine to that of paroxetine in bipolar depressed patients taking mood stabilizers (Vieta et al. 2003). Both seem to be affective add-on therapies, with a slightly higher risk of switch in the venlafaxine group compared with paroxetine group (1/30 versus 4/30 switched to a manic episode, respectively). Additionally, another small (n = 27) randomized trial suggested that using a second mood-stabilizer or an antidepressant in bipolar depressed patients who were already receiving a mood stabilizer was effective (Young et al. 2000). Lastly, in a randomized trial in 117 patients with bipolar depression, imipramine and paroxetine were found to be superior to placebo as add-on therapy, but only in patients whose serum lithium level was <0.8 mEq/L. In patients with a serum lithium level >0.8 mEq/L, there were no differences among the groups (Nemeroff et al. 2001).

Strengths:

• Proven efficacy as acute therapy and maintenance therapy in patients with unipolar depression.
• Generally well tolerated.
• Few drug–drug interactions.

Weaknesses:

• Data on acute therapy are limited and there are no data on controlled maintenance therapy in bipolar depression.
• May cause switching and/or cycle acceleration.

Guidelines

Supporting data