Anti-Depressants, Mood Stabilizers: What Works Best For Bipolar Disorder?

Bipolar disorder, a sometimes debilitating illness marked by severe mood swings between depression and mania, is usually treated with mood stabilizers such as lithium, valproate, carbamazepine or other medications that reduce mania. However, depression is more common than mania in bipolar disorder, and depressive episodes tend to last longer than episodes of mania. Antidepressant medications are often used in addition to a mood stabilizer for treating bipolar depression, but they are thought to confer a serious risk of a switch from a depressive episode to a manic episode.

Finding the right treatment balance for people with bipolar disorder is a constant challenge; STEP-BD aims to identify the best treatment options. "Treating depression in people with bipolar disorder is notoriously difficult," said NIMH Director Thomas R. Insel. "STEP-BD sought to determine if adding an antidepressant to a mood stabilizer is effective and safe in treating depressive episodes. The results suggest that antidepressants are safe but not more effective than placebo as assessed in a large number of people with bipolar disorder. "

Lead author Gary Sachs, M.D., of Massachusetts General Hospital and colleagues studied 366 participants at 22 sites across the country. Unlike most clinical studies, participants were recruited from clinical settings and were included in the study even if they were being treated for co-existing disorders such as substance abuse, anxiety or psychotic symptoms. Such open recruitment criteria allows the study's results to have broader applicability than a tightly controlled trial in which people are excluded from participating if they have co-existing disorders.

Before participants were randomized to one of two antidepressants--bupropion (Wellbutrin) or paroxetine (Paxil)--or to a placebo, doctors trained in the treatment of bipolar disorder adjusted participants' mood stabilizer doses to optimal levels, ensuring that they were receiving the most appropriate amount.

After about 26 weeks, Sachs and colleagues found that 24 percent of those who had been randomized to the antidepressants stayed well for at least eight consecutive weeks--the study's stringent standard for recovery; 27 percent of those randomized to a placebo stayed well long enough to meet the eight-week recovery standard, indicating no difference between adding an antidepressant or adding placebo. In addition, about 10 percent of each group experienced emerging symptoms of mania, indicating that the antidepressants did not trigger a manic switch any more than placebo. Finally, when comparing the two antidepressants to each other, both showed similar rates of response and manic switch.

"Results of STEP-BD indicate that careful management of mood stabilizer medications is a reasonable alternative to adding an antidepressant medication for treating bipolar depression," said Dr. Sachs.

Future STEP-BD results will shed light on other treatment options for bipolar disorder, including psychotherapeutic treatments.

Sachs G, et al. Effectiveness of Adjunctive Antidepressant Treatment for Bipolar Depression: A Double-blind Placebo-controlled Study. New England Journal of Medicine. online 28 Mar 2007.