Mixed depression: clinical features and treatment response in a prospective observational study on bipolar and unipolar patients

Objective. The primary aim of the study was to compare the demographic and clinical characteristics and the treatment outcomes between patients with mixed depression (MxD) based on Koukopoulos’ criteria and non-mixed depression (non-MxD). The secondary aim was to determine whether the clinical characteristic of patients with unipolar MxD bring them closer to the bipolar spectrum disorders.

Methods. A total of 241 outpatients with Major Depressive Disorder (MDD) (51%) and Bipolar Disorder (BD) (49%) disorder, meeting DSM-5 criteria for a current major depressive episode (MDE), were recruited and treated in a prospective observational study. Demographic and clinical characteristics were compared between patients with MxD and non-MxD using chi-square tests, and Mann-Whitney U tests. Treatment safety and effectiveness were assessed after 12 weeks, overall and stratified by MDD and BD.

Results. Irritable or hyperthymic temperament, mixed depression as polarity of onset and as polarity of successive recurrences, and a more severe index episode were the key clinical features differentiating MxD (48% of the sample) from non-MxD. No significant differences were found in treatment received, treatment safety and effectiveness at 12 weeks between MxD and non-MxD patients, both overall and within subgroups. The characteristics of MxD, in particular irritable temperament, suggested that the co-occurrence of (hypo)manic symptoms in unipolar depression identifies patients who should be more appropriately classified within the bipolar spectrum disorders

Conclusions. Our study identifies some key clinical features that distinguish MxD from non-MxD and suggests that patients with unipolar MxD should be more appropriately classified within the bipolar spectrum disorder.