Gobbi G, et al. - This study was performed to compare the efficacy of antidepressant combination vs. antidepressants plus second-generation antipsychotic augmentation in treatment-resistant unipolar depression. In a severe treatment-resistant unipolar depression (TRD) with psychotic features, substance use disorders (SUD), and personality disorders, the augmentation of second-generation antipsychotics ought to be shown as a first-line treatment because of the greater improvement in depression following second-generation antipsychotics plus AD (SGA+AD) augmentation.

• A naturalistic study was performed on the latest stable trial (medication unchanged for about 3 months) in 86 TRD patients with resistance to at least two ADs trials, who received ADs (n=36) or SGA+AD (n=50) treatments.
• They administered Montgomery-Asberg Depression Rating Scale (MADRS), Hamilton-Depression Rating Scale (HAM-D17), and other scales before (T0) and after the latest 3-month stable trial (T3).

• The SGA+AD group demonstrated an increased percentage of depression with psychotic features, comorbidity for personality disorders and substance use disorders (SUD), a higher number of failed ADs pharmacotherapies and depressive symptoms at T0 on all scales (P<0.001) compared to ADs.
• At T3 (P<0.001), both treatments significantly decreased depressive symptoms on MADRS and HAM-D17 compared to T0.
• However, the SGA+AD augmentation produced a greater decline in mean score.
• Logistic regression analysis showed that factors independently associated with SGA+AD treatment were psychotic features, personality disorders, and SUD.