Melancholic Depression and Insomnia as Predictors of Response to Quetiapine in Patients With Major Depression

Summary

In essence the researchers are hoping to test two separate hypotheses (described below in the form of research questions). Therefore, the proposed analysis has been outlined according to each hypothesis. Hypothesis 1: Is low-dose quetiapine (50 mg/day) more effective for patients with depression who have insomnia at treatment baseline? (Stated differently: is low-dose quetiapine 50 mg/day effective as monotherapy for patients with depression regardless of whether or not they have insomnia at baseline?). Hypothesis 2: Is high-dose quetiapine (150 - 300 mg/day) more effective for patients presenting with melancholic depression at treatment baseline?

Timeline

Start

2006-04

Primary completion

2007-07

Completion

2019-10

Outcome

Mixed primary results

registry analysis (superiority test); Quetiapine XR 150-300mg - Melancholic Depression vs Placebo 2 - Melancholic Depression vs Quetiapine XR 150-300mg - Nonmelancholic Depression vs Placebo 2 - Nonmelancholic Depression; p <.001; Hazard Ratio (HR) 1.39; Regression, Cox NCT03207438 ↗

registry analysis (superiority test); Quetiapine XR 50mg - Insomnia vs Quetiapine XR 50mg - No Insomnia; p = .33; Fisher's exact test NCT03207438 ↗

Publications

• Background Trivedi MH, Bandelow B, Demyttenaere K, Papakostas GI, Szamosi J, Earley W, Eriksson H. 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. Int J Neuropsychopharmacol. 2013 Sep;16(8):1733-44. doi: 10.1017/S146114571300028X. Epub 2013 May 14.
• Background Weisler RH, Montgomery SA, Earley WR, Szamosi J, Lazarus A. Efficacy of extended release quetiapine fumarate monotherapy in patients with major depressive disorder: a pooled analysis of two 6-week, double-blind, placebo-controlled studies. Int Clin Psychopharmacol. 2012 Jan;27(1):27-39. doi: 10.1097/YIC.0b013e32834d6f91.
• Background Weisler R, Joyce M, McGill L, Lazarus A, Szamosi J, Eriksson H; Moonstone Study Group. Extended release quetiapine fumarate monotherapy for major depressive disorder: results of a double-blind, randomized, placebo-controlled study. CNS Spectr. 2009 Jun;14(6):299-313. doi: 10.1017/s1092852900020307.
• Background Agargun MY, Kara H, Solmaz M. Sleep disturbances and suicidal behavior in patients with major depression. J Clin Psychiatry. 1997 Jun;58(6):249-51. doi: 10.4088/jcp.v58n0602.
• Background Cutler AJ, Montgomery SA, Feifel D, Lazarus A, Astrom M, Brecher M. Extended release quetiapine fumarate monotherapy in major depressive disorder: a placebo- and duloxetine-controlled study. J Clin Psychiatry. 2009 Apr;70(4):526-39. doi: 10.4088/jcp.08m04592. Epub 2009 Apr 7.
• Background Bortnick B, El-Khalili N, Banov M, Adson D, Datto C, Raines S, Earley W, Eriksson H. Efficacy and tolerability of extended release quetiapine fumarate (quetiapine XR) monotherapy in major depressive disorder: a placebo-controlled, randomized study. J Affect Disord. 2011 Jan;128(1-2):83-94. doi: 10.1016/j.jad.2010.06.031. Epub 2010 Aug 6.
• Background Wang G, McIntyre A, Earley WR, Raines SR, Eriksson H. A randomized, double-blind study of the efficacy and tolerability of extended-release quetiapine fumarate (quetiapine XR) monotherapy in patients with major depressive disorder. Neuropsychiatr Dis Treat. 2014 Jan 30;10:201-16. doi: 10.2147/NDT.S50248. eCollection 2014.
• Background Mallinckrodt CH, Watkin JG, Liu C, Wohlreich MM, Raskin J. Duloxetine in the treatment of Major Depressive Disorder: a comparison of efficacy in patients with and without melancholic features. BMC Psychiatry. 2005 Jan 4;5:1. doi: 10.1186/1471-244X-5-1.
• Background McGrath PJ, Khan AY, Trivedi MH, Stewart JW, Morris DW, Wisniewski SR, Miyahara S, Nierenberg AA, Fava M, Rush AJ. Response to a selective serotonin reuptake inhibitor (citalopram) in major depressive disorder with melancholic features: a STAR*D report. J Clin Psychiatry. 2008 Dec;69(12):1847-55. doi: 10.4088/jcp.v69n1201. Epub 2008 Nov 18.
• Background Brookes ST, Whitely E, Egger M, Smith GD, Mulheran PA, Peters TJ. Subgroup analyses in randomized trials: risks of subgroup-specific analyses; power and sample size for the interaction test. J Clin Epidemiol. 2004 Mar;57(3):229-36. doi: 10.1016/j.jclinepi.2003.08.009.
• Background Royston P, Parmar MK. Restricted mean survival time: an alternative to the hazard ratio for the design and analysis of randomized trials with a time-to-event outcome. BMC Med Res Methodol. 2013 Dec 7;13:152. doi: 10.1186/1471-2288-13-152.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Quetiapine	Small molecule	50 mg	Oral
Subject	Quetiapine	Small molecule	150 mg	Oral
Subject	Quetiapine	Small molecule	300 mg	Oral

Indications