Bipolar surprise: mood disorder endures antidepressant setback.

Contrary to the expectations of many mental-health clinicians, a large-scale study finds that severe depression in patients with bipolar disorder responds no better to a combination of antidepressant medications and mood-stabilizing drugs than it does to mood stabilizers alone.

In another challenge to clinical lore, the federally funded investigation indicates that antidepressant use doesn't hasten the emergence of manic symptoms, such as grandiose thinking and euphoric feelings, in patients with bipolar disorder.

Mild-to-severe versions of bipolar disorder afflict nearly 4 percent of adults at some time in their lives. The illness features swings between periods of depression and mania. Treatment typically includes mood stabilizers such as lithium or other mania-reducing drugs. Clinicians often treat bipolar depression with antidepressants as well, although they have worried that these substances may chemically jolt patients from depression into mania.

Antidepressants are safe to use with mood stabilizers but ease bipolar depression no better than placebo pills do, report psychiatrist Gary S. Sachs of Massachusetts General Hospital in Boston and his colleagues. Their investigation, the largest ever of bipolar disorder, appears online and in the April 26 New England Journal of Medicine.

The researchers studied 366 volunteers diagnosed with bipolar disorder at any of 22 psychiatric centers in the united States. Participants included individuals with severe and moderate forms of mania. Many had also experienced other mental ailments, such as anxiety disorders, substance abuse, and psychosis.

At the start of the study, the volunteers exhibited only symptoms of depression. Physicians first made sure that each patient was taking an appropriate dose of a mood-stabilizing drug. Volunteers then randomly received one of two antidepressants--bupropion (Wellbutrin) or paroxetine (Paxil)--or a placebo.

Most participants also received psychotherapy.

After at most 26 weeks of treatment, 42 of 179 patients receiving antidepressants had shown good emotional health for at least 8 consecutive weeks. Comparable emotional stability characterized 51 of 187 patients receiving placebos. Those response rates weren't significantly different, the researchers calculate.

Only about 10 percent of volunteers taking either antidepressants or placebos shifted quickly from depression into mania.

The results held true whether or not patients attended psychotherapy sessions.

In contrast, research reviews published in 2004 and 2006 reported that antidepressants boost the success of mood stabilizers for bipolar depression. However, the patients whose data were analyzed in those reviews had no psychiatric conditions other than bipolar disorder, often didn't receive psychotherapy, and were tracked for 3 months at most.

"It turns out that antidepressants don't help [patients with bipolar disorder] if they're already taking a mood stabilizer," says psychiatrist Thomas R. Insel, director of the National Institute of Mental Health in Bethesda, Md. Disappointingly, bipolar disorder often resists treatment with any available drug, he adds.

Clinicians must adjust treatment to an individual's symptoms, comments psychiatrist Robert H. Belmaker of Ben Gurion University of the Negev in Beersheba, Israel, in an editorial published with the new report. For example, Belmaker prescribes only antidepressants to patients with severe depression that alternates with mild mania and gives mood stabilizers to most other bipolar patients.