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      Serotonin reuptake inhibitor antidepressants (SSRIs) against atherosclerosis

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          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Summary

          Selective serotonin reuptake inhibitors (SSRIs) are a class of drug widely used for treatment of mood disorders, including depression and cardiovascular disease. A search for related articles in the PubMed database was attempted. It covered studies, reports, reviews and editorials of the last 5 years.

          Pro-inflammatory cytokines, such as TNF-α, IL-1 and IL-6, stimulate central serotonin (5-HT) neurotransmission and are over-expressed in depression, which has been linked with hypothalamic-pituitary-adrenal axis (HPA) hyperactivity. They have also been implicated in the pathogenesis and progression of other stress-induced disorders, like myocardial infarction (MI) and coronary heart disease (CHD), as they seem to modulate cardiovascular function by a variety of mechanisms. Biological mechanisms like these may explain the link between depression and CHD. There are a variety of environmental factors as well as genetic factors that might influence the pharmacogenetics of antidepressant drugs. New generation selective serotonin reuptake inhibitor antidepressants (SSRIs) causing a reduced cardiovascular morbidity and mortality may be related to serotonin platelet abnormalities in depressed patients that are effectively treated by SSRIs. SSRIs such as fluoxetine, paroxetine, sertraline and citalopram are not only considered to be free from the cardiotoxicity of their predecessors but also to function as safe and efficacious agents against depression, platelet activation, atherosclerosis and development and prognosis of coronary heart disease. However, there is a need for more studies in order to establish the exact biochemical mechanisms that are responsible for these diseases and the immunoregulatory effects of chronic use of SSRI medications.

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          Most cited references113

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          Effects of treating depression and low perceived social support on clinical events after myocardial infarction: the Enhancing Recovery in Coronary Heart Disease Patients (ENRICHD) Randomized Trial.

          Depression and low perceived social support (LPSS) after myocardial infarction (MI) are associated with higher morbidity and mortality, but little is known about whether this excess risk can be reduced through treatment. To determine whether mortality and recurrent infarction are reduced by treatment of depression and LPSS with cognitive behavior therapy (CBT), supplemented with a selective serotonin reuptake inhibitor (SSRI) antidepressant when indicated, in patients enrolled within 28 days after MI. Randomized clinical trial conducted from October 1996 to April 2001 in 2481 MI patients (1084 women, 1397 men) enrolled from 8 clinical centers. Major or minor depression was diagnosed by modified Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria and severity by the 17-item Hamilton Rating Scale for Depression (HRSD); LPSS was determined by the Enhancing Recovery in Coronary Heart Disease Patients (ENRICHD) Social Support Instrument (ESSI). Random allocation was to usual medical care or CBT-based psychosocial intervention. Cognitive behavior therapy was initiated at a median of 17 days after the index MI for a median of 11 individual sessions throughout 6 months, plus group therapy when feasible, with SSRIs for patients scoring higher than 24 on the HRSD or having a less than 50% reduction in Beck Depression Inventory scores after 5 weeks. Composite primary end point of death or recurrent MI; secondary outcomes included change in HRSD (for depression) or ESSI scores (for LPSS) at 6 months. Improvement in psychosocial outcomes at 6 months favored treatment: mean (SD) change in HRSD score, -10.1 (7.8) in the depression and psychosocial intervention group vs -8.4 (7.7) in the depression and usual care group (P<.001); mean (SD) change in ESSI score, 5.1 (5.9) in the LPSS and psychosocial intervention group vs 3.4 (6.0) in the LPSS and usual care group (P<.001). After an average follow-up of 29 months, there was no significant difference in event-free survival between usual care (75.9%) and psychosocial intervention (75.8%). There were also no differences in survival between the psychosocial intervention and usual care arms in any of the 3 psychosocial risk groups (depression, LPSS, and depression and LPSS patients). The intervention did not increase event-free survival. The intervention improved depression and social isolation, although the relative improvement in the psychosocial intervention group compared with the usual care group was less than expected due to substantial improvement in usual care patients.
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            Depression and medication adherence in outpatients with coronary heart disease: findings from the Heart and Soul Study.

            Depression leads to adverse outcomes in patients with coronary heart disease (CHD). Medication nonadherence is a potential mechanism for the increased risk of CHD events associated with depression, but it is not known whether depression is associated with medication nonadherence in outpatients with stable CHD. We examined the association between current major depression (assessed using the Diagnostic Interview Schedule) and self-reported medication adherence in a cross-sectional study of 940 outpatients with stable CHD. A total of 204 participants (22%) had major depression. Twenty-eight (14%) of 204 depressed participants reported not taking their medications as prescribed compared with 40 (5%) of 736 nondepressed participants (odds ratio [OR], 2.8; 95% confidence interval [CI], 1.7-4.7; P<.001). Twice as many depressed participants as nondepressed participants (18% vs 9%) reported forgetting to take their medications (OR, 2.4; 95% CI, 1.6-3.8; P<.001). Nine percent of depressed participants and 4% of nondepressed participants reported deciding to skip their medications (OR, 2.2; 95% CI, 1.2-4.2; P = .01). The relationship between depression and nonadherence persisted after adjustment for potential confounding variables, including age, ethnicity, education, social support, and measures of cardiac disease severity (OR, 2.2; 95% CI, 1.2-3.9; P = .009 for not taking medications as prescribed). Depression is associated with medication nonadherence in outpatients with CHD. Medication nonadherence may contribute to adverse cardiovascular outcomes in depressed patients.
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              Evidence for low-grade systemic proinflammatory activity in patients with posttraumatic stress disorder.

              Posttraumatic stress disorder (PTSD) may increase cardiovascular risk but the psychophysiological mechanisms involved are elusive. We hypothesized that proinflammatory activity is elevated in patients with PTSD as diagnosed by the Clinician Administered PTSD Scale (CAPS) interview. Plasma levels of proinflammatory C-reactive protein (CRP), interleukin (IL)-1beta, IL-6, and tumor necrosis factor (TNF)-alpha, and of anti-inflammatory IL-4 and IL-10 were measured in 14 otherwise healthy PTSD patients and in 14 age- and gender-matched healthy non-PTSD controls. Levels of TNF-alpha (p=0.038; effect size Cohen's d=0.58) and of IL-1beta (p=0.075, d=0.68) were higher in patients than in controls. CRP (d=0.10), IL-6 (d=0.18), IL-4 (d=0.42), and IL-10 (d=0.37) were not significantly different between groups. Controlling for traditional cardiovascular risk factors, mood, and time since trauma revealed lower IL-4 in patients than in controls (p=0.029) and rendered group differences in TNF-alpha and IL-1beta insignificant. In all subjects, TNF-alpha correlated with total (frequency and intensity) PTSD symptom cluster of re-experiencing (r=0.49, p=0.008), avoidance (r=0.37, p=0.050), and hyperarousal (r=0.42, p=0.026), and with PTSD total symptom score (r=0.37, p=0.054). Controlling for time since trauma attenuated these associations. The correlation between IL-1beta and total avoidance symptoms (r=0.42, p=0.028) became insignificant when controlling for anxiety and depression. IL-4 correlated with total hyperarousal symptoms (r=-0.38, p=0.047), and after controlling for systolic blood pressure and smoking status, with PTSD total symptom score (r=-0.41, p=0.035). PTSD patients showed a low-grade systemic proinflammatory state, which, moreover, was related to PTSD symptom levels suggesting one mechanism by which PTSD could contribute to atherosclerotic disease.
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                Author and article information

                Journal
                Med Sci Monit
                Med. Sci. Monit
                Medical Science Monitor
                Medical Science Monitor : International Medical Journal of Experimental and Clinical Research
                International Scientific Literature, Inc.
                1234-1010
                1643-3750
                2011
                01 September 2011
                : 17
                : 9
                : RA205-RA214
                Affiliations
                [1 ]Medical School, University of Thessaly, Larissa, Greece
                [2 ]General Hospital of Korinthos, Korinthos, Greece
                [3 ]Psychiatric Department, University of Thessaly, Larissa, Greece
                Author notes
                Greta Wozniak, Medical School, University of Thessaly, 41 110 Mezourlo, Larissa, Greece, e-mail: greta@ 123456med.uth.gr
                Article
                881924
                10.12659/MSM.881924
                3560505
                21873959
                44e2d980-ee2b-4deb-b743-d33acc05009f
                © Med Sci Monit, 2011

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License.

                History
                : 11 March 2011
                : 29 May 2011
                Categories
                Review Article

                ssris,depression,cardiovascular disease,atherosclerosis,tnf-α,immune system

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