Extended-release quetiapine fumarate (quetiapine XR) monotherapy and quetiapine XR or lithium as add-on to antidepressants in patients with treatment-resistant major depressive disorder

Background: Patients with treatment-resistant major depressive disorder (MDD) remain a common clinical challenge. Methods: This 6-week, randomised, open-label, rater-blinded trial evaluated once-daily extended-release quetiapine fumarate (quetiapine XR; 300 mg/day) as add-on to ongoing antidepressant and quetiapine XR monotherapy (300 mg/day) compared with add-on lithium (0.6-12 mmol/L) in patients with treatment-resistant MDD. Primary efficacy measure: change in Montgomery Asberg Depression Rating Scale (MADRS) total score from randomisation to week 6 with a pre-specified non-inferiority limit of 3 points on the MADRS. Results: At week 6, both add-on quetiapine XR (n=231) and quetiapine XR monotherapy (n=228) were non-inferior to add-on lithium (n=229); least squares means (LSM) differences (97.5% Cl) in MADRS total score changes were -2.32 (-4.6, -0.05) and -0.97 (-3.24, 1.31), respectively. LSM MADRS total score change was numerically greater at day 4 for both quetiapine XR groups (add-on and monotherapy; p < 0.01) compared with add-on lithium. At week 6, the differences between groups for the secondary endpoints of MADRS response (>= 50% reduction in total score), MADRS remission (total score <= 10, add-on quetiapine XR only) and Clinical Global Impressions ('much'/'very much' improved) were numerically similar. Overall tolerability was consistent with the known profiles of both treatments. Limitations: Limitations included the open-label study design (although MADRS and laboratory measurements were performed by treatment blinded raters) and relatively short study duration with no assessments in the continuation phase. Conclusions: Add-on quetiapine XR (300 mg/day) and quetiapine XR monotherapy (300 mg/day) are non inferior to add-on lithium in the management of patients with treatment resistant MDD. (C) 2013 Published by Elsevier B.V.