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Protocol for a systematic review and meta-analysis of data from preclinical studies employing forced swimming test: an update
  1. A B Ramos-Hryb1,
  2. Z Bahor2,
  3. S McCann2,
  4. E Sena2,
  5. M R MacLeod2,
  6. C Lino de Oliveira1
  1. 1 Physiological Sciences Deptartment, Biological Sciences Center, Federal University of Santa Catarina, Florianópolis, Brazil
  2. 2 Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK
  1. Correspondence to C Lino de Oliveira, Dept de Ciências Fsisiológicas, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina; cilene.lino{at}


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Objective Forced swimming test (FST) in rodents is a widely used behavioural test for screening antidepressants in preclinical research. Translational value of preclinical studies may be improved by appraisal of the quality of experimental design and risk of biases, which remains to be addressed for FST. The present protocol of a systematic review with meta-analysis aims to investigate the quality of preclinical studies employing FST to identify risks of bias in future publications. In addition, this protocol will help to determine the effect sizes (ES) for primary and secondary outcomes according to several aspects of the FST study design.

Search strategy, Screening annotation, Data management Publications reporting studies testing different classes of antidepressants in FST will be collected from Medline, SCOPUS and Web of Science databases. A broad list of inclusion criteria will be applied excluding those studies whereby FST is used as a stressor or studies reporting data from co-treatments. For assessing the quality of the included publications, the quality checklist adapted by Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies will be used. If the meta-analysis seems feasible, the ES and the 95% CI will be analysed. The heterogeneity between studies will be assessed by using the χ2statistic with n−1 degrees of freedom. Subgroup meta-analysis (meta-regression, and if necessary, stratified regression) will be performed when possible according to characteristics of study design and study quality to assess their impact on efficacy of the treatments. In addition, funnel plotting, Egger regression, and ‘trim and fill’ will be used to assess the risk of publication bias. Results of this protocol will help to create rational methodological guidelines for application of FST in rodents and improve the quality and translational value of preclinical research on antidepressant discovery.

Reporting A preliminary version of the present protocol has been preregistered with Systematic Review Facility ( A preprint version of the current protocol has been registered with Open Science Framework ( Results will be communicated in scientific meetings and peer-reviewed journals. We plan to conduct an anonymous and online survey within the scientific community to ask researchers about their perception of risk of bias and their experience with the publication of negative results.

This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See:

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  • Data availability statement All data relevant to the study are included in the article.

  • Contributors CLdO selected the research theme, designed and performed research, analysed data, wrote the paper, approved the final version of the manuscript. ABR-H wrote the paper, approved the final version of the manuscript. ZB performed research, analysed data, discussed data, revised the paper, approved the final version of the manuscript. SM approved the final version of the manuscript. ES designed the research; discussed data, revised the paper, approved the final version of the manuscript. MRM designed the research; discussed data, revised the paper, approved the final version of the manuscript.

  • Funding This research group received funds from CNPq, Capes, Fapesc (Brazilian public agencies for research), Alexander von Humboldt Foundation (Germany) and Newton International Exchanges (Royal Society, UK).

  • Competing interests None declared.

  • Open data Open data are available at

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