Effect Of SSRIs On Autonomic Nervous System - Info and Reading Options

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Background/Aims Hannah Campbell PhD, Marco Solmi MD, Dimitri Fiani MD, Jess Gerard Fiedorowicz MD, Chadi Calarge MD Psychiatric conditions such as depression has been associated with increased morbidity and mortality due to co-morbid medical illness including cardiovascular disease. This may be in part due to changes in cardiac autonomic regulation found in patients with psychiatric illness. However, evidence has suggested that this change in autonomic regulation, as often measured by changes in heart rate variability (HRV), may be in part secondary to the effects of antidepressant treatment. However, while the effect of serotonin norepinephrine reuptake inhibitors and tricyclic antidepressants on the autonomic nervous system has been established, data regarding the effects of selective serotonin reuptake inhibitors (SSRIs) on autonomic nervous system activity has been more varied in the literature. Therefore, we aim to conduct a systematic review and meta-analysis to examine the available evidence regarding the effect of SSRIs on autonomic nervous system activity as measured through HRV. We also aim to examine the contribution of gender, psychiatric diagnosis, presence of cardiovascular disease, age, and treatment duration on the heterogeneity between studies. Review question Is there an association between SSRIs and HRV, across different clinical populations, and compared with non-clinical population? Searches PubMed, Scopus, Google scholar Search Terms to be used: (“selective serotonin reuptake inhibitors” or “antidepressants” or “citalopram” or “escitalopram” or “fluoxetine” or “fluvoxamine” or “paroxetine” or “sertraline” or SSRI) AND (“autonomic” or “heart rate variability” or “HRV”) Inclusion Criteria Study Design Randomized controlled trials, cohort studies, cross-sectional studies Participants/population Any population receiving a treatment with SSRIs Intervention(s), exposure(s) SSRIs Comparator(s)/control Clinical psychiatric or medical population without SSRI, or non-clinical population, or SSRI status within the same population (pre-post) Main outcome(s) HRV, without any restrictions in measure Data extraction Two reviewers will search literature and determine if studies meet inclusion/exclusion criteria (H.C., D.F.). If discrepancies, a third collaborator (M.S.) will be asked to resolve. The following data will be extracted: study design, population, medication type(s), doses, duration of treatment, stress conditions, psychiatric diagnosis, anxiety and or depression scale, overall population demographics, outcome data including all reported parameters of heart rate variability, descriptive results of secondary-outcome measures, effect sizes. Risk of bias (quality) assessment Cohort studies will be evaluated using the Newcastle Ottawa scale. Controlled intervention studies are to be evaluated using the NIH-NHLBI quality assessment tools. Two evaluators will work independently to assess quality (H.C., D.F.). Strategy for data synthesis/statistical analysis When at least two studies with the same design and PICO combination will report on HRV we will pool them in a random-effect meta-analysis and calculate pooled Cohen’s d with Comprehensive Meta-Analysis (CMA). If unable to perform meta-analysis on similar outcome measurements, we will report results descriptively. Controlled trials vs cohort studies vs pre-post studies will be analyzed and reported separately. Heterogeneity will be assessed using standard I2 calculations. Additional sensitivity analyses include subgrouping by medication, psychiatric diagnosis, medical diagnosis, age, gender, treatment duration, stress vs. non-stressed measurement. Contact details for further information, Hannah Campbell [email protected] Organizational affiliation of the review Baylor College of Medicine Type and method of review Meta-analysis, Systematic review Anticipated or actual start date September 28 2021 Anticipated completion date December 2021 Funding sources/sponsors None Conflicts of interest None known Language English Country United States of America Stage of review Review Ongoing Date of registration in OSF September 28, 2021

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