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To address this gap, we plan a systematic review and individual-participant-data network meta-analysis to investigate their comparative effectiveness in real-world emergency settings with increased precision.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>We will include randomized controlled trials investigating intramuscular or intravenous pharmacological interventions, as monotherapy or in combination, in adults with severe psychomotor agitation irrespective of the underlying diagnosis and requiring rapid tranquilization in general or psychiatric emergency settings. We will exclude studies before 2002, those focusing on specific reasons for agitation and placebo-controlled trials to avoid concerns related to the transitivity assumption and potential selection biases. We will search for eligible studies in BIOSIS, CENTRAL, CINAHL Plus, Embase, LILACS, MEDLINE via Ovid, PubMed, ProQuest, PsycINFO, ClinicalTrials.gov, and WHO-ICTRP. Individual-participant data will be requested from the study authors and harmonized into a uniform format, and aggregated data will also be extracted from the studies. At least two independent reviewers will conduct the study selection, data extraction, risk-of-bias assessment using RoB 2, and applicability evaluation using the RITES tool. The primary outcome will be the number of patients achieving adequate sedation within 30\u00a0min after treatment, with secondary outcomes including the need for additional interventions and adverse events, using odds ratios as the effect size. If enough individual-participant data will be collected, we will synthesize them in a network meta-regression model within a Bayesian framework, incorporating study- and participant-level characteristics to explore potential sources of heterogeneity. In cases where individual-participant data are unavailable, potential data availability bias will be explored, and models allowing for the inclusion of studies reporting only aggregated data will be considered. We will assess the confidence in the evidence using the Confidence in Network Meta-Analysis (CINeMA) approach.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Discussion<\/jats:title>\n                <jats:p>This individual-participant-data network meta-analysis aims to provide a fine-tuned synthesis of the evidence on the comparative effectiveness of pharmacological interventions for severe psychomotor agitation in real-world emergency settings. The findings from this study can greatly be provided clearer evidence-based guidance on the most effective treatments.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Systematic review registration<\/jats:title>\n                <jats:p>PROSPERO CRD42023402365.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13643-024-02623-z","type":"journal-article","created":{"date-parts":[[2024,8,2]],"date-time":"2024-08-02T10:09:32Z","timestamp":1722593372000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Effectiveness of pharmacological treatments for severe agitation in real-world emergency settings: protocol of individual-participant-data network meta-analysis"],"prefix":"10.1186","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8264-2039","authenticated-orcid":false,"given":"Spyridon","family":"Siafis","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuyuki","family":"Nomura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Schneider-Thoma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Bighelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolin","family":"Lorenz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph E.","family":"Dib","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prathap","family":"Tharyan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonie A.","family":"Calver","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geoffrey K.","family":"Isbister","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther W. 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Hui Wu, none\u00a0reported. Nobuyuki Nomura has received speaker fees from Eisai, Meiji Seika Pharma, Otsuka, and Sumitomo Pharma and manuscript fees from Sumitomo Pharma. Johannes Schneider-Thoma, none\u00a0reported. Irene Bighelli, none\u00a0reported. Carolin Lorenz, none\u00a0reported. Joseph E. Dib is author of potentially eligible trials and no other conflicts of interest\u00a0reported. Prathap Tharyan is author of potentially eligible trials and no other conflicts of interest\u00a0reported. Leonie A. Calver is author of potentially eligible trials and no other conflicts of interest\u00a0reported. Geoffrey K. Isbister is author of potentially eligible trials and no other conflicts of interest\u00a0reported. Esther W. Y. Chan reports grants from the Hong Kong Research Grants Council of the Government of the Hong Kong SAR, Research Fund Secretariat of the Food and Health Bureau, National Natural Science Fund of China, Wellcome Trust, Bayer, Bristol-Myers Squibb, Pfizer, Janssen, Amgen, Takeda, RGA Reinsurance Company, AstraZeneca, Narcotics Division of the Security Bureau of the Hong Kong Special Administrative Region, Innovation and Technology Commission of the Government of the Hong Kong Special Administrative Region, Novartis, and National Health and Medical Research Council Australia and honorarium from Hospital Authority, outside the submitted work. E. W. Y. C. is also author of potentially eligible trials. Jonathan C. Knott is author of potentially eligible trials and no other conflicts of interest\u00a0reported. Celene Y. L. Yap is author of potentially eligible trials and no other conflicts of interest\u00a0reported. C\u00e9lia Mantovani is author of potentially eligible trials and no other conflicts of interest\u00a0reported. Marc L. Martel is author of potentially eligible trials and no other conflicts of interest. David Barbic is author of potentially eligible trials and no other conflicts of interest\u00a0reported. William G. Honer has served as a consultant to Translational Life Sciences, Newron, AbbVie, and Boehringer Ingelheim. W. G. H. is also author of potentially eligible trials\u00a0reported. Wulf-Peter Hansen, none\u00a0reported. Gisele Huf is author of potentially eligible trials and no other conflicts of interest\u00a0reported. Jacob Alexander is author of potentially eligible trials and no other conflicts of interest\u00a0reported. Nirmal S. Raveendran is author of potentially eligible trials and no other conflicts of interest\u00a0reported. Evandro S. F. Coutinho is author of potentially eligible trials and no other conflicts of interest\u00a0reported. Josef Priller, none\u00a0reported. Clive E. Adams is author of potentially eligible trials and no other conflicts of interest\u00a0reported. Georgia Salanti, none\u00a0reported. Stefan Leucht has in the last 3 years\u00a0received honoraria for advising\/consulting and\/or for lectures and\/or for educational material from Angelini, Boehringer Ingelheim, Eisai, Ekademia, Gedeon Richter, Janssen, Karuna, Kynexis, Lundbeck, Medichem, Medscape, Mitsubishi, Otsuka, Novo Nordisk, Recordati, Rovi, and Teva.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"205"}}