title: The international Study to Predict Optimized Treatment in Depression (iSPOT-D): outcomes from the acute phase of antidepressant treatment.
abstract: We aimed to characterize a large international cohort of outpatients with MDD within a practical trial design, in order to identify clinically useful predictors of outcomes with three common antidepressant medications in acute-phase treatment of major depressive disorder (MDD). The international Study to Predict Optimized Treatment in Depression has presently enrolled 1008 treatment-seeking outpatients (18-65 years old) at 17 sites (five countries). At pre-treatment, we characterized participants by symptoms, clinical history, functional status and comorbidity. Participants were randomized to receive escitalopram, sertraline or venlafaxine-extended release and managed by their physician following usual treatment practices. Symptoms, function, quality of life, and side-effect outcomes were assessed 8 weeks later. The relationship of anxiety to response and remission was assessed by comorbid Axis I diagnosis, presence/absence of anxiety symptoms, and dimensionally by anxiety symptom severity. The sample had moderate-to-severe symptoms, but substantial comorbidity and functional impairment. Of completers at week 8, 62.2% responded and 45.4% reached remission on the 17-item Hamilton Rating Scale for Depression; 53.3% and 37.6%, respectively on the 16-item Quick Inventory of Depressive Symptoms. Functional improvements were seen across all domains. Most participants had side effects that occurred with a frequency of 25% or less and were reported as being in the "none" to minimal/mild range for intensity and burden. Outcomes did not differ across medication groups. More severe anxiety symptoms at pre-treatment were associated with lower remission rates across all medications, independent of depressive severity, diagnostic comorbidity or side effects. Across medications, we found consistent and similar improvements in symptoms and function, and a dimensional prognostic effect of comorbid anxiety symptoms. These equivalent outcomes across treatments lay the foundation for identifying potential neurobiological and genetic predictors of treatment outcome in this sample.
authors.affiliation: Department of Psychiatry, The Ohio State University College of Medicine, Columbus, OH 43210, USA.
authors.forename: Radu
authors.initials: R
authors.lastname: Saveanu
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA; Sierra-Pacific Mental Illness Research, Education, and Clinical Center (MIRECC) Veterans Affairs Palo Alto Health Care System, Palo Alto, CA 94304, USA.
authors.forename: Amit
authors.initials: A
authors.lastname: Etkin
authors.affiliation: Department of Psychiatry, The Ohio State University College of Medicine, Columbus, OH 43210, USA.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Duchemin
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA; Sierra-Pacific Mental Illness Research, Education, and Clinical Center (MIRECC) Veterans Affairs Palo Alto Health Care System, Palo Alto, CA 94304, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Goldstein-Piekarski
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA; Sierra-Pacific Mental Illness Research, Education, and Clinical Center (MIRECC) Veterans Affairs Palo Alto Health Care System, Palo Alto, CA 94304, USA.
authors.forename: Anett
authors.initials: A
authors.lastname: Gyurak
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Charles
authors.initials: C
authors.lastname: Debattista
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Alan F
authors.initials: AF
authors.lastname: Schatzberg
authors.affiliation: SHANTI Clinical Trials, Colton, CA 92324, USA.
authors.forename: Satish
authors.initials: S
authors.lastname: Sood
authors.affiliation: Brain Dynamics Center, Psychiatry, University of Sydney Medical School at Westmead Hospital, Sydney, NSW 2145, Australia; Brain Resource Ltd, 235 Jones Street, Sydney, NSW, Australia; Brain Resource Inc, 1000 Sansome Street, San Francisco, CA 94111, USA.
authors.forename: Claire V A
authors.initials: CV
authors.lastname: Day
authors.affiliation: Brain Dynamics Center, Psychiatry, University of Sydney Medical School at Westmead Hospital, Sydney, NSW 2145, Australia; Brain Resource Ltd, 235 Jones Street, Sydney, NSW, Australia; Brain Resource Inc, 1000 Sansome Street, San Francisco, CA 94111, USA.
authors.forename: Donna M
authors.initials: DM
authors.lastname: Palmer
authors.affiliation: Brain Resource Ltd, 235 Jones Street, Sydney, NSW, Australia; Brain Resource Inc, 1000 Sansome Street, San Francisco, CA 94111, USA.
authors.forename: William R
authors.initials: WR
authors.lastname: Rekshan
authors.affiliation: Brain Resource Ltd, 235 Jones Street, Sydney, NSW, Australia; Brain Resource Inc, 1000 Sansome Street, San Francisco, CA 94111, USA.
authors.forename: Evian
authors.initials: E
authors.lastname: Gordon
authors.affiliation: Duke-NUS Graduate Medical School, 8 College Road, Singapore 169857, Singapore.
authors.forename: A John
authors.initials: AJ
authors.lastname: Rush
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA; Sierra-Pacific Mental Illness Research, Education, and Clinical Center (MIRECC) Veterans Affairs Palo Alto Health Care System, Palo Alto, CA 94304, USA; Brain Dynamics Center, Psychiatry, University of Sydney Medical School at Westmead Hospital, Sydney, NSW 2145, Australia. Electronic address: leawilliams@stanford.edu.
authors.forename: Leanne M
authors.initials: LM
authors.lastname: Williams
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000928:Antidepressive Agents / Q000627:therapeutic use*; D001007:Anxiety / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D015331:Cohort Studies; D015897:Comorbidity; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000523:psychology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011897:Random Allocation; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000928:Antidepressive Agents
keywords: Escitalopram; International practical trial; Major depressive disorder; Response and remission; Sertraline; Venlafaxine-XR