Evaluate the effects of once-daily extended release quetiapine fumarate (quetiapine XR) monotherapy on sleep disturbance in patients with major depressive disorder (MDD).

Pooled data from four 6- or 8-week placebo-controlled quetiapine XR (50-300mg/day, administered in the evening) monotherapy studies (D1448C00001, D1448C00002, D1448C00003, D1448C00004) were analysed. Primary endpoint: change from randomisation in Montgomery-Åsberg Depression Rating Scale (MADRS) scores. Post-hoc analyses assessed changes in: MADRS item 4 (reduced sleep); Hamilton Rating Scale for Depression (HAM-D) items 4 (insomnia-early), 5 (insomnia-middle) and 6 (insomnia-late) and sleep disturbance factor (items 4+5+6); Pittsburgh Sleep Quality Index (PSQI) total and item scores. MADRS total score change was analysed for patients experiencing high (baseline HAM-D sleep disturbance factor score >=4) and low (baseline HAM-D sleep disturbance factor score < 4) sleep disturbance.

In total, 2,116 patients were randomised. At last assessment, quetiapine XR (all doses combined) significantly (p< 0.001) reduced MADRS item 4, HAM-D sleep disturbance factor and items 4, 5 and 6 and PSQI total scores from baseline versus placebo. Quetiapine XR significantly (p< 0.001) improved MADRS total score from baseline versus placebo at all time points in patients experiencing high sleep disturbance (n=865, quetiapine XR; n=514, placebo). Quetiapine XR improved MADRS total score versus placebo in patients with low sleep disturbance (n=252, quetiapine; n=121, placebo): difference significant at Weeks 2(p< 0.001), 4(p< 0.05) and 6(p< 0.05).

Quetiapine XR monotherapy improved symptoms of sleep disturbance in MDD and was effective against depressive symptoms in patients experiencing high and low sleep disturbance levels. AstraZeneca funded.