title: Cognitive-Behavioural Analysis System of Psychotherapy (CBASP), a drug, or their combination: differential therapeutics for persistent depressive disorder: a study protocol of an individual participant data network meta-analysis.
abstract: Despite important advances in psychological and pharmacological treatments of persistent depressive disorders in the past decades, their responses remain typically slow and poor, and differential responses among different modalities of treatments or their combinations are not well understood. Cognitive-Behavioural Analysis System of Psychotherapy (CBASP) is the only psychotherapy that has been specifically designed for chronic depression and has been examined in an increasing number of trials against medications, alone or in combination. When several treatment alternatives are available for a certain condition, network meta-analysis (NMA) provides a powerful tool to examine their relative efficacy by combining all direct and indirect comparisons. Individual participant data (IPD) meta-analysis enables exploration of impacts of individual characteristics that lead to a differentiated approach matching treatments to specific subgroups of patients.
  
  
  
  We will search for all randomised controlled trials that compared CBASP, pharmacotherapy or their combination, in the treatment of patients with persistent depressive disorder, in Cochrane CENTRAL, PUBMED, SCOPUS and PsycINFO, supplemented by personal contacts. Individual participant data will be sought from the principal investigators of all the identified trials. Our primary outcomes are depression severity as measured on a continuous observer-rated scale for depression, and dropouts for any reason as a proxy measure of overall treatment acceptability. We will conduct a one-step IPD-NMA to compare CBASP, medications and their combinations, and also carry out a meta-regression to identify their prognostic factors and effect moderators. The model will be fitted in OpenBUGS, using vague priors for all location parameters. For the heterogeneity we will use a half-normal prior on the SD.
  
  
  
  This study requires no ethical approval. We will publish the findings in a peer-reviewed journal. The study results will contribute to more finely differentiated therapeutics for patients suffering from this chronically disabling disorder.
  
  
  
  CRD42016035886.
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 Psychiatry and Psychotherapy, University Medical Center Freiburg, Freiburg, Germany.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Schramm
authors.affiliation: Department of Clinical, Neuro and Developmental Psychology, EMGO Institute for Health and Care Research, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
authors.forename: Erica S
authors.initials: ES
authors.lastname: Weitz
authors.affiliation: Institute of Social and Preventive Medicine (ISPM) & Bern Institute of Primary Care (BIHAM), University of Bern, Bern, Switzerland.
authors.forename: Georgia
authors.initials: G
authors.lastname: Salanti
authors.affiliation: Institute of Social and Preventive Medicine (ISPM) & Bern Institute of Primary Care (BIHAM), University of Bern, Bern, Switzerland.
authors.forename: Orestis
authors.initials: O
authors.lastname: Efthimiou
authors.affiliation: Department of Psychology and Psychotherapy, Witten/Herdecke University, Witten, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Michalak
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: Andrea
authors.identifier: 0000-0001-5179-8321
authors.initials: A
authors.lastname: Cipriani
authors.affiliation: Department of Psychiatry and Human Behavior, Brown University, Providence, Rhode Island, USA.
authors.forename: Martin B
authors.initials: MB
authors.lastname: Keller
authors.affiliation: Department of Psychiatry, Weill Cornell Medical College, New York, New York, USA.
authors.forename: James H
authors.initials: JH
authors.lastname: Kocsis
authors.affiliation: Department of Psychology, Stony Brook University, Stony Brook, New York, USA.
authors.forename: Daniel N
authors.initials: DN
authors.lastname: Klein
authors.affiliation: Department of Clinical, Neuro and Developmental Psychology, EMGO Institute for Health and Care Research, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
authors.forename: Pim
authors.initials: P
authors.lastname: Cuijpers
mesh_terms: D015928:Cognitive Behavioral Therapy; D003131:Combined Modality Therapy; D003866:Depressive Disorder / Q000503:physiopathology / Q000523:psychology / Q000628:therapy*; D004358:Drug Therapy; D006801:Humans; D017063:Outcome Assessment, Health Care; D011613:Psychotherapy; D016032:Randomized Controlled Trials as Topic; D000078202:Systematic Reviews as Topic; D013597:Systems Analysis; D000071076:Network Meta-Analysis as Topic
keywords: Differential therapeutics; Systematic review