Antidepressant-induced hypomania/mania in patients with major depression: Evidence from the BRIDGE-II-MIX study

Background: The issue of antidepressant-induced mood switches to hypomania, mania, or mixed states within the course of mayor depressive disorder (MDD) has been a controversial topic. The present post-hoc analysis of the BRIDGE-II-MIX study focuses on the clinical features of patients with history of antidepressant-induced hypomania/mania (AIHM) in a large international sample of patients with major depressive episode (MDE). Methods: 2811 subjects with major depression were enrolled in this multicentre cross-sectional study. Current mixed symptoms, socio-demographic and other clinical variables were collected and compared among MDD-AIHM, MDD and BD patients. Results: 475 patients out of 2811 had history of AIHM (16.90%). In the MDD-AIHM group, familiarity for BD and rates of atypical features and comorbid anxiety, eating and borderline personality disorders were similar to BD and significantly more frequent compared to MDD group. MDD-AIHM patients had more frequently more than 3 episodes and reported higher rates of treatment resistance, mood lability and irritability following treatment with antidepressants. Frequencies of depression with mixed features and (hypo) manic symptoms were similar in patients of MDD-AIHM and BD groups and significantly higher in both groups than in MDD. Limitations: there were widely varying rates of hospitalized patients across countries and the participating centres were not randomly selected. Conclusions: Our results strongly support the DSM-5 inclusion of MDD patients with AIHM within the rubric of bipolar disorder. Differences with other MDD and BD were also observed suggesting the possibility that MDD-AIHM may represent a specific sub-population, particularly sensitive to exogenous input from antidepressants.