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      Selective serotonin reuptake inhibitors and cardiovascular events: A systematic review

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          Abstract

          Background:

          Given the importance of the role of depression in predicting the outcome of cardiovascular disorders, current medications for treating depression, particularly selective serotonin reuptake inhibitors (SSRIs), are taken into consideration. This study aimed to systematically review the published findings in the use of SSRIs and the risk for cardiac events.

          Materials and Methods:

          An independent review of the Web of Science, PubMed, Scopus, Cochrane, CINAHL, index Copernicus, and Google Scholar, up to 2014, was performed. We identified studies evaluating the effect of SSRIs, on cardiovascular events. Articles in English with full text availability, review articles, and experimental studies were included in the study. Among 150 studies reviewed based on the included keywords, 17 met the study criteria and were finally reviewed.

          Results:

          The use of some types of SSRIs may prevent platelet adhesion and aggregation; control the cardiovascular risk profile including hypertension, insulin resistance, and body weight; and also inhibit inflammatory processes. The appearance of adverse cardiac events, including cardiac arrhythmias (torsade de pointes and QT prolongation), syncope, increased systolic and diastolic right ventricular volume, and the production of pro-inflammatory cytokines leading atherosclerosis development, has also been expected with the chronic use of some types of SSRIs.

          Conclusion:

          According to our systematic review, both beneficial and adverse cardiovascular events can be established following the chronic use of various types of SSRIs. Therefore, when taking SSRIs, the cardiovascular effect of each SSRI has to be carefully considered, based on patients’ cardiovascular risk profiles.

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          Most cited references46

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          Empirical evidence of bias. Dimensions of methodological quality associated with estimates of treatment effects in controlled trials.

          To determine if inadequate approaches to randomized controlled trial design and execution are associated with evidence of bias in estimating treatment effects. An observational study in which we assessed the methodological quality of 250 controlled trials from 33 meta-analyses and then analyzed, using multiple logistic regression models, the associations between those assessments and estimated treatment effects. Meta-analyses from the Cochrane Pregnancy and Childbirth Database. The associations between estimates of treatment effects and inadequate allocation concealment, exclusions after randomization, and lack of double-blinding. Compared with trials in which authors reported adequately concealed treatment allocation, trials in which concealment was either inadequate or unclear (did not report or incompletely reported a concealment approach) yielded larger estimates of treatment effects (P < .001). Odds ratios were exaggerated by 41% for inadequately concealed trials and by 30% for unclearly concealed trials (adjusted for other aspects of quality). Trials in which participants had been excluded after randomization did not yield larger estimates of effects, but that lack of association may be due to incomplete reporting. Trials that were not double-blind also yielded larger estimates of effects (P = .01), with odds ratios being exaggerated by 17%. This study provides empirical evidence that inadequate methodological approaches in controlled trials, particularly those representing poor allocation concealment, are associated with bias. Readers of trial reports should be wary of these pitfalls, and investigators must improve their design, execution, and reporting of trials.
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            Major depression in individuals with chronic medical disorders: prevalence, correlates and association with health resource utilization, lost productivity and functional disability.

            The objective of this study was to determine the prevalence and odds of major depression and the incremental effect of major depression on utilization, lost productivity and functional disability in individuals with common chronic medical disorders. Data on 30,801 adults from the 1999 National Health Interview Survey were analyzed. The 12-month prevalence and age/sex-adjusted odds of major depression were calculated for adults with hypertension (HTN), diabetes mellitus (DM), coronary artery disease (CAD), congestive heart failure (CHF), stroke or cerebrovascular accident (CVA), chronic obstructive pulmonary disease (COPD) and end-stage renal disease (ESRD). The association between chronic condition status (with and without major depression) and utilization, lost productivity and functional disability was determined by controlling for covariates. The 12-month prevalence and age/sex-adjusted odds of major depression by chronic conditions were as follows: CHF, 7.9% [odds ratio (OR)=1.96]; HTN, 8.0% (OR=2.00); DM, 9.3% (OR=1.96); CAD, 9.3% (OR=2.30); CVA, 11.4% (OR=3.15); COPD, 15.4% (OR=3.21); ESRD, 17.0% (OR=3.56); any chronic condition, 8.8% (OR=2.61). Compared to adults without chronic conditions, those with chronic conditions plus major depression had greater odds of > or = 1 ambulatory visit [OR=1.50; 95% confidence interval (95% CI)=1.28, 1.77]; > or = 1 emergency room visit (OR=1.94; 95% CI=1.55, 2.45); and > or = 1 day in bed due to illness (OR=1.60; 95% CI=1.28, 2.00); and functional disability (OR=2.48; 95% CI=1.96, 3.15). The 12-month prevalence and odds of major depression are high in individuals with chronic medical conditions, and major depression is associated with significant increases in utilization, lost productivity and functional disability.
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              Cytokine imbalance in the pathophysiology of major depressive disorder.

              A substantial body of evidence indicates that dysregulation of the immune system is associated with Major Depressive Disorder (MDD). Because most cytokines have pleiotropic effects, we measured various subsets of cytokines to examine the association between immune response and MDD. Forty-eight hospitalized MDD patients and 63 normal controls were recruited. We measured in vitro monocytic (IL-6 and tumor necrosis factor (TNF)-alpha), Th1 (interferon (IFN)-gamma and interleukin (IL)-2), Th2 (IL-4), and Treg (transforming growth factor (TGF)-beta1) cytokine production as well as IL-2/IL-4 and IFN-gamma/IL-4 ratios for both groups. Depressive symptoms were assessed by Hamilton Depression Rating Scale. Patients were evaluated before and after 6 weeks of antidepressant treatment. At admission, IL-6, TNF-alpha, TGF-beta1 production, and IFN-gamma/IL-4 ratio were significantly higher, whereas IFN-gamma, IL-2, and IL-4 were significantly lower in MDD patients. After treatment, IL-6 and TGF-beta1 production were significantly lower than before treatment. We suggest that activation of monocytic proinflammatory cytokines, and inhibition of both Th1 and Th2 cytokines may be associated with immunological dysregulation in MDD. TGF-beta1 may be associated with the regulation of monocytic cytokines as well as Th1 and Th2 cytokines in MDD.
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                Author and article information

                Journal
                J Res Med Sci
                J Res Med Sci
                JRMS
                Journal of Research in Medical Sciences : The Official Journal of Isfahan University of Medical Sciences
                Medknow Publications & Media Pvt Ltd (India )
                1735-1995
                1735-7136
                2016
                01 September 2016
                : 21
                : 66
                Affiliations
                [1 ]Department of Cardiac Surgery, Imam Reza Hospital, Mashhad University of Medical Sciences, Mashhad, Iran
                [2 ]Atherosclerosis Prevention Research Center, Imam Reza Hospital, Mashhad University of Medical Sciences, Mashhad, Iran
                [3 ]Department of Pediatric Cardiology, Islamic Azad University, Mashhad Branch, Mashhad, Iran
                [4 ]Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran
                Author notes
                Address for correspondence: Pouya Nezafati, Department of Cardiac Surgery, Imam Reza Hospital, Ibn Sina Boulevard, P.O. Box: 9137913316, Mashhad, Iran. E-mail: pouya.nezafati@ 123456gmail.com
                Article
                JRMS-21-66
                10.4103/1735-1995.189647
                5122239
                27904611
                92e12192-b6b8-4fcc-983b-6335baa7c0a4
                Copyright: © Journal of Research in Medical Sciences

                This is an open access article distributed under the terms of the Creative Commons Attribution NonCommercial ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non commercially, as long as the author is credited and the new creations are licensed under the identical terms.

                History
                : 30 November 2015
                : 06 March 2016
                : 25 May 2016
                Categories
                Review Article

                Medicine
                cardiovascular,drug,selective serotonin reuptake inhibitor
                Medicine
                cardiovascular, drug, selective serotonin reuptake inhibitor

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