Medications and individual factors associated with serotonin syndrome: a protocol for an overview of reviews

<ns3:p> Introduction Serotonin syndrome is a potentially lethal adverse drug reaction caused by exposure to one or more serotonin-elevating medications. Its burden is unknown due to the absence of official diagnostic criteria, under-reporting and symptom overlap with other syndromes. This overview of reviews aims to summarise published systematic review evidence on drugs and risk factors commonly associated with serotonin syndrome and to determine its incidence. Methods Searches will be conducted in Medline (OVID), Embase, the Cochrane Database of Systematic Reviews, PsycInfo and Epistemonikos. PROSPERO will also be searched for ongoing reviews. Systematic reviews reporting the incidence of serotonin syndrome in patients treated with at least one serotonin-elevating drug will be included. The quality of included systematic reviews will be assessed using the JBI’s critical appraisal checklist for Systematic Reviews and Research Syntheses. Two reviewers will independently conduct title/abstract screening and full text review. Data extraction will be conducted as a multi-stage process from the included systematic reviews as well as from eligible primary studies within systematic reviews, according to the overview objectives. The results will be synthesised both narratively and quantitatively using random effects models. We will present pooled estimates with 95% CIs for binary data and mean difference or standardised mean difference with 95% CIs for continuous data. The results will be presented in forest plots to assess their heterogeneity. Statistical heterogeneity will be assessed with I <ns3:sup>2</ns3:sup> statistics. Ethics and dissemination No ethical approval will be required. The results will be disseminated through open-access peer-review journals and conferences. </ns3:p>