Although antidepressants are often prescribed for depression in patients with bipolar disorder, many clinicians remain concerned about risk of antidepressant-induced mood-switching to mania.

Dr. Amsterdam presented data from two double-blind studies of patients with type II bipolar disorder that showed no evidence of higher rates of mood-switching in patients treated with venlafaxine or fluoxetine than in patients treated with placebo.

Examining data on fluoxetine-treated patients from manufacturer's records dating back to the launch of fluoxetine in the U.S. in early 1988, Amsterdam identified 89 patients with bipolar II depression who had taken a fixed fluoxetine dosage of 20 mg/day. He found that those patients showed lower rates of depressive recurrence over a six-month follow-up duration than did patients who were being treated with fluoxetine for unipolar depression. During acute treatment, 3.8% of bipolar patients developed hypomania, which resolved spontaneously during continued treatment with fluoxetine.

Amsterdam next discussed a study in patients with unipolar depression or bipolar II depression who were assigned to treatment with either venlafaxine or placebo. Rates of mood-switching to mania were zero for both bipolar and unipolar patients treated with venlafaxine. Antidepressant response rates were similar in bipolar and unipolar patients.

Turning his attention to monoamine oxidase inhibitors (MAOI's), Amsterdam discussed studies by Zoll and colleagues in the early 1970's that found MAOI's highly effective for bipolar depression. As with fluoxetine and venlafaxine, rates of mood-switching to mania were low in patients with bipolar depression during treatment with MAOI's. Moreover, rates of mood-switching were similar in patients taking MAOI's alone and in patients co-treated with lithium.

In the early 1990s, University of Pittsburgh researchers compared imipramine with MAOI's in 56 patients with bipolar depression and found higher antidepressant response rates in MAOI-treated patients. MAOI's were as well tolerated as imipramine and were associated with a low rate of mood-switching to mania.