title: Depression symptom clusters and their predictive value for treatment outcomes: results from an individual patient data meta-analysis of duloxetine trials.
abstract: We evaluated individual patient data from phase II to IV clinical trials of duloxetine in major depressive disorder (MDD) (34 studies, 13,887 patients). Our goal was to identify clusters of patients with similar depressive symptom patterns at baseline, as measured by the 17-item Hamilton Depression Rating Scale (HAMD-17), and to investigate their respective predictive value of outcomes as measured by the HAMD-17 total score. Five clusters were identified at baseline: 1) "Lack of insight"; 2) "Sleep/sexual/somatic"; 3) "Typical MDD"; 4) "Gastrointestinal/weight loss"; and 5) "Mild MDD". However, it should be noted that cluster descriptors are not mutually exclusive. Analyses of the HAMD-17 total score results over time were performed using the 18 randomized placebo and/or actively controlled studies representing 6723 patients. At the end of acute treatment (ranging from 4 to 36 weeks), different levels of effect sizes for active therapy (64.5% duloxetine) vs. placebo were detected by cluster. In 3 out of 5 clusters (representing about 80% of the patients), the effect size was significantly different from 0, in favor of active therapy. The effect size was largest in those clusters with severe somatic symptoms ("Sleep/sexual/somatic" cluster [-0.4170], and "Gastrointestinal/weight loss" cluster [-0.338]). In conclusion, our cluster analysis identified 5 clinically relevant MDD patient clusters with specific mean treatment outcomes. Identification of MDD clusters may help to improve outcomes by adapting MDD treatment to particular clinical profiles.
authors.affiliation: Lilly Deutschland GmbH, Global Statistical Sciences, Bad Homburg, Germany. Electronic address: SCHACHT_ALEXANDER@LILLY.COM.
authors.forename: Alexander
authors.initials: A
authors.lastname: Schacht
authors.affiliation: Sainte-Anne Hospital (CMME), Paris Descartes University, INSERM UMR894, Paris, France.
authors.forename: Philip
authors.initials: P
authors.lastname: Gorwood
authors.affiliation: University of Sydney, Sydney Medical School, Discipline of Psychiatry, Sydney, NSW, Australia; Westmead Hospital, Department of Psychiatry, Wentorthville, NSW, Australia.
authors.forename: Philip
authors.initials: P
authors.lastname: Boyce
authors.affiliation: University of Toronto, Sunnybrook Health Sciences Centre, Department of Psychiatry, Toronto, ON, Canada.
authors.forename: Ayal
authors.initials: A
authors.lastname: Schaffer
authors.affiliation: 21 Chesterford Gardens, NW3 7DD, London, UK.
authors.forename: Hernan
authors.initials: H
authors.lastname: Picard
mesh_terms: D002986:Clinical Trials as Topic; D016000:Cluster Analysis; D016208:Databases, Factual / Q000706:statistics & numerical data; D003863:Depression / Q000188:drug therapy*; D000068736:Duloxetine Hydrochloride; D005260:Female; D006801:Humans; D008297:Male; D011237:Predictive Value of Tests; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*; D013876:Thiophenes / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000068736:Duloxetine Hydrochloride; D017367:Selective Serotonin Reuptake Inhibitors; D013876:Thiophenes
keywords: Cluster analysis; Depression; Duloxetine; Hamilton Depression Rating Scale (HAMD); Major depressive disorder (MDD)