Residual Depressive Symptoms in Bipolar Depression

To the Editor: Ramin Mojtabai, M.D., Ph.D. (1), recently reported important data on residual symptoms in major depression in the community. Overall, 34% of respondents whose last major depressive episode had ended had residual depressive symptoms, and 23% had residual symptoms for more than 1 year. Unipolar major depressive disorder has been the main focus of studies of residual depressive symptoms (1, 2). In clinical study groups, residual depressive symptoms were reported to be common in unipolar depression (1, 2).

Bipolar II depression has recently been reported to be much more common in depressed outpatients than has been previously reported, with a frequency ranging from 30% to 55% (3, 4). The study of residual depressive symptoms is, therefore, also very important in this common disorder. In my recent study (5), 44.9% of outpatients with bipolar II disorder who were seen for treatment of a major depressive episode in a private practice (a setting closer to the community than tertiary care settings) (N=138) had residual depressive symptoms for more than 2 years from the index major depressive episode. (In the updated group of patients with bipolar II disorder [N=206], 43.6% had had residual depressive symptoms for more than 2 years.) Persistent residual depressive symptoms in bipolar II depression were significantly (p<0.001) and positively associated with illness duration and number of recurrences. These findings have important treatment implications. Prevention of major depressive episodes and treatment of residual depressive symptoms could reduce recurrences and, thus, reduce further residual symptoms and impairment.

However, the use of antidepressants may be a problem for patients with bipolar II depression, because antidepressants may induce hypomania, mixed states, and rapid cycling, and aggressive antidepressant treatments are more likely in patients with long-lasting depression (3). Consequently, antidepressants may induce mood instability when used in the treatment of residual depressive symptoms in bipolar II patients and may require concurrent treatment with mood stabilizers to prevent or reduce mood instability. Clinicians should know that residual depressive symptoms are common also in bipolar II depression (frequently in depressed outpatients) and that treatment of residual depressive symptoms in bipolar II patients may be more complicated than in patients with unipolar depression. Skillful, structured questioning by clinicians about past hypomania during a depression assessment, supplemented by information from family members and/or close friends, is required to increase the bipolar II case findings (3, 4) and to prevent the possible negative effects of antidepressants on bipolar II depression that is misdiagnosed as unipolar depression.