Bipolar mixed episodes and antidepressants: a cohort study of bipolar I disorder patients

The aim of this study was to elucidate the factors associated with the occurrence of mixed episodes, characterized by the presence of concomitant symptoms of both affective poles, during the course of illness in bipolar I disorder patients treated with an antidepressant, as well as the role of antidepressants in the course and outcome of the disorder.

We enrolled a sample of 144 patients followed for up to 20 years in the referral Barcelona Bipolar Disorder Program and compared subjects who had experienced at least one mixed episode during the follow-up (n=60) with subjects who had never experienced a mixed episode (n=84) regarding clinical variables.

Nearly 40% of bipolar I disorder patients treated with antidepressants experienced at least one mixed episode during the course of their illness; no gender differences were found between two groups. Several differences regarding clinical variables were found between the two groups, but after performing logistic regression analysis, only suicide attempts (p<0.001), the use of serotonin norepinephrine reuptake inhibitors (p=0.041), switch rates (p=0.010), and years spent ill (p=0.022) were significantly associated with the occurrence of at least one mixed episode during follow-up.

The occurrence of mixed episodes is associated with a tendency to chronicity, with a poorer outcome, a higher number of depressive episodes, and greater use of antidepressants, especially serotonin norepinephrine reuptake inhibitors.