Although depression is the major burden of bipolar disorder for many patients, most studies show that antidepressants do not improve outcome for either depression or mania in bipolar patients. However, a subgroup of bipolar II patients does respond to antidepressants. Amsterdam and Shults (p. 792) report that this subgroup continues to have less recurrence of depression when they are treated with fluoxetine than if they are switched to lithium or placebo (figure, below). In an editorial (p. 738), Trisha Suppes points out that even in this subgroup, selected for a prior response to fluoxetine, maintenance treatment with fluoxetine results in more mood instability than occurs with lithium or placebo. Nonetheless, they appear to have an overall positive course with antidepressant treatment.