Bipolar depression and antidepressant-induced mania: a naturalistic study.

Background: The likelihood and character of antidepressant-induced mania remain important but poorly understood factors in the treatment of bipolar depression.

Method: We examined the response to naturalistic treatment of 29 bipolar I patients who experienced a total of 79 depressive episodes. Treatment consisted primarily of mood stabilizers used alone (N = 31) or in combination with antidepressants (N = 48). Intensity of baseline mood stabilizer therapy, adequacy of added antidepressant therapy, intensity of ensuing mania or hypomania, and course of illness prior to study were measured, and selected comparisons were made between treatment groups.

Results: Postdepressive mood elevations (i.e., switches) that occurred during or up to 2 months after each depressive episode were present in 28% (22/79) and judged to be severely disruptive in only 10% (8/79) of episodes. Examining only the first episode per patient, a history of a greater number of past manic episodes was associated with a higher risk of switching (p < .023). Antidepressant treatment combined with mood stabilizer therapy was not associated with higher rates of postdepressive mood elevation than mood stabilizer therapy alone. At a descriptive level, subjects treated with tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs) were associated with a higher switch rate than those treated with fluoxetine; TCAs were also associated with more intense switches.

Conclusion: The frequency and severity of postdepressive mood elevation associated with acute or continuation antidepressant therapy may be reduced by mood stabilizers. Such elevations may be more likely in patients with a strong history of mania.