title: Evaluation of the effects of extended release quetiapine fumarate monotherapy on sleep disturbance in patients with major depressive disorder: a pooled analysis of four randomized acute studies.
abstract: Effects of once-daily extended-release quetiapine fumarate (quetiapine XR) monotherapy on sleep quality and disturbance in patients with major depressive disorder (MDD) were evaluated. Pooled data from four 6- or 8-wk placebo-controlled quetiapine XR (50-300 mg/d) monotherapy studies (D1448C00001; D1448C00002; D1448C00003; D1448C00004) were analysed. Primary efficacy end-point was change from randomization in Montgomery Åsberg Depression Rating Scale (MADRS) score. Post hoc analyses of secondary end-points were conducted for change from randomization in: MADRS item 4 (reduced sleep); Hamilton Rating Scale for Depression (HAMD) items 4 (insomnia-early), 5 (insomnia-middle), 6 (insomnia-late) and sleep disturbance factor (items 4 + 5+6) scores; Pittsburgh Sleep Quality Index (PSQI) global scores. MADRS total score change was also evaluated in patients experiencing high and low baseline sleep disturbance (HAMD sleep disturbance factor scores ⩾4 and < 4, respectively). In total, 1808 patients were randomized to quetiapine XR or placebo across four studies. At last assessment, quetiapine XR reduced MADRS item 4, HAMD items 4, 5 and 6, HAMD sleep disturbance factor score and PSQI global scores from baseline vs. placebo (p < 0.001). For those experiencing high sleep disturbance (n = 865, quetiapine XR; n = 514, placebo), quetiapine XR improved MADRS total score vs. placebo at all visits (p < 0.001). For those with low sleep disturbance (n = 252, quetiapine XR; n = 121, placebo), quetiapine XR improved MADRS total score vs. placebo at weeks 2 (p < 0.001), 4 and 6 (both p < 0.05). In conclusion, quetiapine XR (50-300 mg/d) monotherapy improved symptoms of sleep disturbance vs. placebo in patients with MDD, including those with either high or low baseline sleep disturbance levels.
authors.affiliation: Department of Psychiatry, UT Southwestern Medical Center, Dallas, TX 75390, USA. madhukar.trivedi@utsouthwestern.edu
authors.forename: Madhukar H
authors.initials: MH
authors.lastname: Trivedi
authors.forename: Borwin
authors.initials: B
authors.lastname: Bandelow
authors.forename: Koen
authors.initials: K
authors.lastname: Demyttenaere
authors.forename: George I
authors.initials: GI
authors.lastname: Papakostas
authors.forename: George I
authors.initials: GI
authors.lastname: Papakosts
authors.forename: Johan
authors.initials: J
authors.lastname: Szamosi
authors.forename: Willie
authors.initials: W
authors.lastname: Earley
authors.forename: Hans
authors.initials: H
authors.lastname: Eriksson
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D014150:Antipsychotic Agents / Q000008:administration & dosage*; D003865:Major Depressive Disorder / Q000150:complications / Q000188:drug therapy*; D003987:Dibenzothiazepines / Q000008:administration & dosage*; D004311:Double-Blind Method; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D016018:Least-Squares Analysis; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D000069348:Quetiapine Fumarate; D012720:Severity of Illness Index; D012893:Sleep Wake Disorders / Q000150:complications / Q000188:drug therapy*; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D000069348:Quetiapine Fumarate