Fluoxetine to Prevent Relapse of Bipolar II Depression?

Practice guidelines recommend antidepressant maintenance for recovered patients with unipolar depression, but they generally discourage these drugs in patients with bipolar depression. Many antidepressant studies have lumped together patients with bipolar I and II disorders, and those trials focusing on bipolar II disorder have had divergent results: Some suggest benefits, while others indicate an increase in mood switches during antidepressant use, even with concurrent mood stabilizers. In this government-funded investigation, researchers reexamined the issue.

The initial phase involved fluoxetine monotherapy (20–80 mg/day) in 148 carefully selected patients with bipolar II disorder (mean age, 37). After 12 weeks, only initial responders (n=83) were permitted to move to phase 2; of these, 81 were randomized to double-blind fluoxetine monotherapy (10–40 mg/day) for 50 weeks or to discontinuation of fluoxetine and subsequent treatment with lithium (300–1200 mg/day; target serum levels, 0.5–1.5 mmol/L) or placebo. The mean time to full syndromal depressive relapse or recurrence was 250 days with fluoxetine, 187 days with placebo, and 156 days with lithium. Relapse occurred in 32% of patients on fluoxetine, 52% of patients on placebo, and 58% of lithium recipients. Ten patients developed hypomania (fluoxetine, 3; lithium, 2; placebo, 5), and treatment was discontinued in one fluoxetine recipient and one placebo recipient.