A pooled analysis of two randomised, placebo-controlled studies of extended release quetiapine fumarate adjunctive to antidepressant therapy in patients with major depressive disorder

Background: Two positive studies evaluated adjunctive extended release quetiapine fumarate (quetiapine XR) in patients with major depressive disorder (MDD) showing inadequate response to antidepressant treatment. This preplanned, pooled analysis provides an opportunity for subgroup analyses investigating the influence of demographic and disease-related factors on observed responses. Additional post hoc analyses examined the efficacy of quetiapine XR against specific depressive symptoms including sleep. Methods: Data were analysed from two 6-week, multicentre, double-blind, randomised, placebo-controlled studies, prospectively designed to be pooled. Patients received once-daily quetiapine XR 150 mg/day (n = 309), 300 mg/day (n = 307) or placebo (n = 303) adjunctive to ongoing antidepressant therapy. The primary endpoint was change from randomisation to Week 6 in MADRS total score. Other assessments included MADRS response (>= 50% decrease in total score) and remission (total score 8), change from randomisation in HAM-D, HAM-A, PSQI global and CGI-S scores. Results: Quetiapine XR (150 and 300 mg/day) reduced MADRS total scores vs placebo at every assessment including Week 6 (- 14.5, - 14.8. - 12.0; p < 0.001 each dose) and Week 1 (-7.8, -7.3,-5.1; p<0.001 each dose). For quetiapine XR 150 and 300 mg/day and placebo, respectively at Week 6: MADRS response 53.7% (p = 0.063), 583% (p < 0.01) and 46.2%; MADRS remission 35.6% (p < 0.01), 36.5% (p < 0.001) and 24.1%. Quetiapine XR 150 and 300 mg/day significantly improved HAM-D, HAM-A, PSQI and CGI-S scores at Week 6 vs placebo. Quetiapine XR demonstrated broad efficacy, independent of factors including concomitant antidepressant. Limitations: Fixed dosing; lack of active comparator. Conclusions: Adjunctive quetiapine XR is effective in patients with MDD and an inadequate response to antidepressant therapy, with improvement in depressive symptoms seen as early as Week 1. (C) 2010 Elsevier B.V. All rights reserved.