To evaluate the efficacy and tolerability of once-daily quetiapine XR (extended release) monotherapy in patients with MDD (unipolar depression) compared with placebo.

8-week (6-week active treatment, randomised phase; 2-week post-treatment drug-discontinuation/tapering phase), multicentre, double-blind, parallel-group, placebo- and active-controlled study (D1448C00002). 612 patients were randomised to quetiapine XR 150mg/day (n=152), 300mg/day (n=152), duloxetine 60mg/day (n=151) and placebo (n=157). Primary endpoint: baseline to Week 6 change in MADRS total score. Secondary variables included: baseline to Week 6 change in HAM-D total and Item 1 (depressed mood) scores. Safety assessments included AE reporting.

Mean MADRS total score (overall baseline mean, 30.15) was significantly reduced at Week 6 by quetiapine XR 150mg/day, 300mg/day and duloxetine versus placebo (−14.81, −15.29, −14.64, −11.18, respectively; p≤0.001).

At Week 6, mean HAM-D total scores (overall baseline mean, 25.25) were significantly reduced versus placebo (−10.26) by quetiapine XR 150mg/day, 300mg/day (−13.12, −14.02, respectively, p≤0.001) and duloxetine (−12.37, p<0.05). Mean HAM-D item 1 scores (overall baseline mean, 3.03) were significantly reduced versus placebo (−1.07) by quetiapine XR 150mg/day, 300mg/day (−1.49, −1.56, respectively, p≤0.001) and duloxetine (−1.53, p<0.001).

Incidence of serious AEs were low (≤2%) in all groups. Most common AEs (>10%) were dry mouth, sedation, somnolence, dizziness, headache and nausea with quetiapine; dizziness and headache with placebo; and dry mouth, sedation, somnolence, dizziness, headache, constipation, nausea, diarrhoea and insomnia with duloxetine. Most AEs were mild-to-moderate in intensity.

Quetiapine XR monotherapy at 150 and 300mg/day was effective and well tolerated in the treatment of patients with MDD.