Although depression is a major component of the burden of bipolar disorder, a critical point that needs to be carefully considered in assessing the overall benefit of each treatment is the prevention of mood instability. Amsterdam and Shults clearly define criteria for hypomania and subsyndromal hypomania. Using a Young Mania Rating Scale threshold of ≥8, fluoxetine-treated patients were three times more likely than lithium-treated patients to have a hypomanic study visit; the findings were also present, but attenuated, using a threshold ≥12. Overall, the proportion of patients receiving fluoxetine meeting their various definitions of hypomania was 50% versus about 34% for those patients on blinded lithium or placebo (Table 3: including events noted of mood lability, subsyndromal hypomania, or hypomania). Does this mean fluoxetine treatment prevented the recurrence of depression, but at the risk of some degree of mood instability? This conclusion is reinforced by the Young Mania Rating Scale individual profile plots (Figure 3), which show noticeably greater excursions above 0 for fluoxetine and for placebo, compared to lithium.