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Psychosocial treatments for relapse prevention in schizophrenia: study protocol for a systematic review and network meta-analysis of randomised evidence
  1. Irene Bighelli1,
  2. Alessandro Rodolico2,
  3. Gabi Pitschel-Walz1,
  4. Wulf-Peter Hansen3,
  5. Corrado Barbui4,
  6. Toshi A Furukawa5,
  7. Georgia Salanti6,
  8. Stefan Leucht1
  1. 1Department of Psychiatry and Psychotherapy, School of Medicine, Klinikum rechts der Isar der Technischen Universitat Munchen, Munchen, Germany
  2. 2Department of Clinical and Experimental Medicine, Institute of Psychiatry, University of Catania, Catania, Sicilia, Italy
  3. 3BASTA—Bündnis für psychisch erkrankte Menschen, Munich, Germany
  4. 4WHO Collaborating Centre for Research and Training in Mental Health and Service Evaluation, Department of Neuroscience, Biomedicine and Movement Sciences, Section of Psychiatry, University of Verona, Verona, Italy
  5. 5Department of Health Promotion and Human Behavior, Kyoto University Graduate School of Medicine / School of Public Health, Japan, Kyoto, Japan
  6. 6Institute of Social and Preventive Medicine (ISPM), University of Bern, Bern, Switzerland
  1. Correspondence to Dr Irene Bighelli; irene.bighelli{at}


Introduction There is evidence that different psychosocial interventions could reduce the risk of relapse in schizophrenia, but a comprehensive evidence based on their relative efficacy is lacking. We will conduct a network meta-analysis (NMA), integrating direct and indirect comparisons from randomised controlled trials (RCTs) to rank psychosocial treatments for relapse prevention in schizophrenia according to their efficacy, acceptability and tolerability.

Methods and analysis We will include all RCTs comparing a psychosocial treatment aimed at preventing relapse in patients with schizophrenia with another psychosocial intervention or with a no treatment condition (waiting list, treatment as usual). We will include studies on adult patients with schizophrenia, excluding specific subpopulations (eg, acutely ill patients). Primary outcome will be the number of patients experiencing a relapse. Secondary outcomes will be acceptability (dropout), change in overall, positive, negative and depressive symptoms, quality of life, adherence, functioning and adverse events. Published and unpublished studies will be sought through database searches, trial registries and websites. Study selection and data extraction will be conducted by at least two independent reviewers. We will conduct random-effects NMA to synthesise all evidence for each outcome and obtain a comprehensive ranking of all treatments. NMA will be conducted in R within a frequentist framework. The risk of bias in studies will be evaluated using the Cochrane Risk of Bias tool and the credibility of the evidence will be evaluated using Confidence in Network Meta-Analysis (CINeMA). Subgroup and sensitivity analyses will be conducted to assess the robustness of the findings.

Ethics and dissemination No ethical issues are foreseen. Results from this study will be published in peer-reviewed journals and presented at relevant conferences.

PROSPERO registration number CRD42019147884.

  • schizophrenia & psychotic disorders
  • adult psychiatry
  • statistics & research methods

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See:

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  • Collaborators Samantha Roberts helped us to conduct the literature searches. Johannes Schneider-Thoma, Maximilian Huhn, Spyridon Siafis and Helena García-Mieres provided help and suggestions. Members of the patient organisation BASTA contributed providing the patients’ perspective.

  • Contributors IB and SL designed this study, drafted and critically revised the protocol. GS provided substantial methodological and statistical advice. AR, GP-W, CB and TAF contributed with clinical and methodological input in planning the study. W-PH provided input from patients’ point of view. All authors contributed to and have approved the final manuscript.

  • Funding This work was supported by the German Ministry for Education and Research (Bundesministerium für Bildung und Forschung, BMBF), grant number FKZ 01KG1803.

  • Competing interests SL has received honoraria as a consultant/advisor and/or for lectures from LB Pharma, Otsuka, Lundbeck, Boehringer Ingelheim, LTS Lohmann, Janssen, Johnson and Johnson, TEVA, MSD, Sandoz, SanofiAventis, Angelini, Sunovion, Recordati and Gedeon Richter. TAF reports personal fees from Meiji, Mitsubishi-Tanabe, MSD and Pfizer and a grant from Mitsubishi-Tanabe, outside the submitted work, and has a patent 2018-1 77 688 pending.

  • Patient consent for publication Not required.

  • Ethics approval This review does not require ethical approval.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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