title: Comparative efficacy and acceptability of first-generation and second-generation antidepressants in the acute treatment of major depression: protocol for a network meta-analysis.
abstract: Many antidepressants are indicated for the treatment of major depression. Two network meta-analyses have provided the most comprehensive assessments to date, accounting for both direct and indirect comparisons; however, these reported conflicting interpretation of results. Here, we present a protocol for a systematic review and network meta-analysis aimed at updating the evidence base and comparing all second-generation as well as selected first-generation antidepressants in terms of efficacy and acceptability in the acute treatment of major depression.
  
  
  
  We will include all randomised controlled trials reported as double-blind and comparing one active drug with another or with placebo in the acute phase treatment of major depression in adults. We are interested in comparing the following active agents: agomelatine, amitriptyline, bupropion, citalopram, clomipramine, desvenlafaxine, duloxetine, escitalopram, fluoxetine, fluvoxamine, levomilnacipran, milnacipran, mirtazapine, nefazodone, paroxetine, reboxetine, sertraline, trazodone, venlafaxine, vilazodone and vortioxetine. The main outcomes will be the proportion of patients who responded to or dropped out of the allocated treatment. Published and unpublished studies will be sought through relevant database searches, trial registries and websites; all reference selection and data extraction will be conducted by at least two independent reviewers. We will conduct a random effects network meta-analysis to synthesise all evidence for each outcome and obtain a comprehensive ranking of all treatments. To rank the various treatments for each outcome, we will use the surface under the cumulative ranking curve and the mean ranks. We will employ local as well as global methods to evaluate consistency. We will fit our model in a Bayesian framework using OpenBUGS, and produce results and various checks in Stata and R. We will also assess the quality of evidence contributing to network estimates of the main outcomes with the GRADE framework.
  
  
  
  This review does not require ethical approval.
  
  
  
  CRD42012002291.
authors.affiliation: Department of Health Promotion and Human Behavior, Kyoto University Graduate School of Medicine/School of Public Health, Kyoto, Japan.
authors.forename: Toshi A
authors.identifier: 0000-0003-2159-3776
authors.initials: TA
authors.lastname: Furukawa
authors.affiliation: Department of Clinical Research, Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland Institute of Primary Health Care (BIHAM), University of Bern, Switzerland Department of Hygiene and Epidemiology, University of Ioannina, Ioannina, Greece.
authors.forename: Georgia
authors.initials: G
authors.lastname: Salanti
authors.affiliation: Department of Psychiatry, University of Oxford, Oxford, UK.
authors.forename: Lauren Z
authors.initials: LZ
authors.lastname: Atkinson
authors.affiliation: Department of Psychiatry and Psychotherapy, TU- Munich, Munchen, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Leucht
authors.affiliation: Department of Psychiatry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands University Center for Psychiatry, University of Groningen, Groningen, The Netherlands.
authors.forename: Henricus G
authors.initials: HG
authors.lastname: Ruhe
authors.affiliation: Behavioral Health and Neurosciences Division, VA Portland Health Care System, Portland, Oregon, USA Departments of Psychiatry and Pharmacology, Oregon Health & Science University, Portland, Oregon, USA.
authors.forename: Erick H
authors.initials: EH
authors.lastname: Turner
authors.affiliation: Department of Hygiene and Epidemiology, University of Ioannina, Ioannina, Greece.
authors.forename: Anna
authors.initials: A
authors.lastname: Chaimani
authors.affiliation: Department of Health Promotion and Human Behavior, Kyoto University Graduate School of Medicine/School of Public Health, Kyoto, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Ogawa
authors.affiliation: Department of Health Promotion and Human Behavior, Kyoto University Graduate School of Medicine/School of Public Health, Kyoto, Japan.
authors.forename: Nozomi
authors.initials: N
authors.lastname: Takeshima
authors.affiliation: Department of Health Promotion and Human Behavior, Kyoto University Graduate School of Medicine/School of Public Health, Kyoto, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Hayasaka
authors.affiliation: Department of Health Promotion and Human Behavior, Kyoto University Graduate School of Medicine/School of Public Health, Kyoto, Japan.
authors.forename: Hissei
authors.initials: H
authors.lastname: Imai
authors.affiliation: Department of Health Promotion and Human Behavior, Kyoto University Graduate School of Medicine/School of Public Health, Kyoto, Japan.
authors.forename: Kiyomi
authors.initials: K
authors.lastname: Shinohara
authors.affiliation: Department of Health Promotion and Human Behavior, Kyoto University Graduate School of Medicine/School of Public Health, Kyoto, Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Suganuma
authors.affiliation: Department of Health Promotion and Human Behavior, Kyoto University Graduate School of Medicine/School of Public Health, Kyoto, Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Watanabe
authors.affiliation: Department of Psychiatry, University of Oxford, Oxford, UK.
authors.forename: Sarah
authors.initials: S
authors.lastname: Stockton
authors.affiliation: Department of Psychiatry, University of Oxford, Oxford, UK Oxford Health NHS Foundation Trust, Warneford Hospital, Oxford, UK.
authors.forename: John R
authors.initials: JR
authors.lastname: Geddes
authors.affiliation: Department of Psychiatry, University of Oxford, Oxford, UK Oxford Health NHS Foundation Trust, Warneford Hospital, Oxford, UK.
authors.forename: Andrea
authors.identifier: 0000-0001-5179-8321
authors.initials: A
authors.lastname: Cipriani
mesh_terms: D006801:Humans; D000928:Antidepressive Agents / Q000627:therapeutic use; D018687:Antidepressive Agents, Second-Generation / Q000627:therapeutic use; D001499:Bayes Theorem; D003865:Major Depressive Disorder / Q000188:drug therapy; D000071076:Network Meta-Analysis as Topic; D016896:Treatment Outcome; D000078202:Systematic Reviews as Topic
chemical_list: D000928:Antidepressive Agents; D018687:Antidepressive Agents, Second-Generation
keywords: Antidepressants; Major depression; Network meta-analysis; Systematic review