Am J Psychiatry Published November 17, 2008

Correlates of Treatment-Emergent Mania Associated With Antidepressant Treatment in Bipolar Depression

Mark A. Frye, M.D., Gerhard Helleman, Ph.D., Susan L. McElroy, M.D., Lori L. Altshuler, M.D., David O. Black, Ph.D., Paul E. Keck , Jr., M.D., Willem A. Nolen, M.D., Ph.D., Ralph Kupka, M.D., Ph.D., Gabriele S. Leverich, L.C.S.W., Heinz Grunze, M.D., Jim Mintz, Ph.D., Robert M. Post, M.D., and Trisha Suppes, M.D., Ph.D.

Objective: Treatment-emergent mania can have substantial negative impact on overall mood and psychosocial stability in patients receiving treatment for bipolar depression. This study examined the correlates associated with treatment-emergent mania in patients receiving adjunctive antidepressant treatment for bipolar depression. Method: A total of 176 adult outpatients with bipolar disorder in a 10-week trial of adjunctive antidepressant treatment for depression were categorized into three groups based on the Clinical Global Impression Scale for Bipolar Disorder: those who responded to antidepressant treatment (N=85), those who did not respond to antidepressant treatment (N=45), and those who had treatment-emergent mania or hypomania (N=46). Symptom severity was measured with the Inventory of Depressive Symptomatology and the Young Mania Rating Scale (YMRS) at baseline and bimonthly intervals. Factor analysis was used to examine correlates of treatment-emergent mania.

Results: Baseline YMRS scores were significantly different between groups. Otherwise, there were no significant between-group differences in demographic or clinical characteristics. Factor analysis showed that a subset of the YMRS items predicted treatment-emergent mania in this sample: increased motor activity, speech, and language-thought disorder.

Conclusions: These data suggest that minimal manic symptoms at baseline coexisting with otherwise full syndromal bipolar depression are associated with antidepressant treatment-emergent mania or hypomania. A careful examination of motor activation, pressured speech, and racing thoughts is warranted before starting antidepressant treatment in bipolar depression