Mixed hypomania in 908 patients with bipolar disorder evaluated prospectively in the Stanley Foundation Bipolar Treatment Network: A sex-specific phenomenon

Context: The prevalence of depressive symptoms co-occurring with hypomanic symptoms has not been quantified. Whether there is a greater likelihood for women to experience mixed symptoms has not been resolved. Objectives: To determine whether mixed hypomania is observed more frequently than euphoric hypomania and whether a sex effect exists in patients with bipolar disorder. Setting: Academic research settings in the United States (4 sites) and Europe (3 sites). Participants: Subjects were enrolled in a naturalistic prospective study after providing written informed consent. Main Outcome Measures: Mixed hypomania was defined at a given visit as a Young Mania Rating Scale score of 12 or higher and an Inventory of Depressive Symptomatology-Clinician-Rated Version score of 15 or higher. Given partial overlap of items from these scales, exploratory analyses were completed assessing instrument overlap affecting the findings. Results: In 908 patients, 14 328 visits over 7 years were evaluated. Patients with bipolar I disorder were significantly more likely to experience hypomania than those with bipolar II disorder. Of all 1044 visits by patients with hypomanic symptoms, 57% met criteria for mixed hypomania. The likelihood of depression was significantly greater for women during hypomania (P<.001). For women, the probability of mixed symptoms increased with the severity of hypomania and then decreased at the most severe levels of hypomania or mania. When a modified Inventory of Depressive Symptomatology-Clinician-Rated Version was evaluated by removing the 5 overlapping Young Mania Rating Scale items, a significant sex effect persisted for women (P<.001) but not for men (P=.95), owing to the elimination of the items "irritability" and "agitation." Conclusions: Mixed hypomania is common in patients with symptoms of hypomania and particularly common in women. Potential overlap of clinical symptom scales should be assessed before study of patients with bipolar disorder symptoms is undertaken.