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      Depression, Antidepressant Use and Mortality in Later Life: The Health in Men Study

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          Abstract

          Context

          Depression is associated with increased mortality, but it is unclear if this relationship is dose-dependent and if it can be modified by treatment with antidepressants.

          Objective

          To determine if (1) the association between depression and mortality is independent of other common potential causes of death in later life, (2) there is a dose-response relationship between increasing severity of depression and mortality rates, and (3) the use of antidepressant drugs reduces mortality rates.

          Methods

          Cohort study of 5,276 community-dwelling men aged 68–88 years living in Perth, Australia. We used the Geriatric Depression Scale 15-items (GDS-15) to ascertain the presence and severity of depression. GDS-15≥7 indicates the presence of clinically significant depression. Men were also grouped according to the severity of symptoms: “no symptoms” (GDS-15 = 0), “questionable” (1≤GDS-15≤4), “mild to moderate” (5≤GDS-15≤9), and “severe” (GDS-15≥10). Participants listed all medications used regularly. We used the Western Australian Data Linkage System to monitor mortality.

          Results

          There were 883 deaths between the study assessment and the 30th June 2008 (mean follow-up of participants: 6.0±1.1 years). The adjusted mortality hazard (MH) of men with clinically significant depression was 1.98 (95%CI = 1.61–2.43), and increased with the severity of symptoms: 1.39 (95%CI = 1.13–1.71) for questionable, 2.71 (95%CI = 2.13–3.46) for mild/moderate, and 3.32 (95%CI: 2.31–4.78) for severe depression. The use of antidepressants increased MH (HR = 1.31, 95%CI = 1.02–1.68). Compared with men who were not depressed and were not taking antidepressants, MH increased from 1.22 (95%CI = 0.91–1.63) for men with no depression who were using antidepressants to 1.85 (95%CI = 1.47–2.32) for participants who were depressed but were not using antidepressants, and 2.97 (95%CI = 1.94–4.54) for those who were depressed and were using antidepressants. All analyses were adjusted for age, educational attainment, migrant status, physical activity, smoking and alcohol use and the Charlson comorbidity index.

          Conclusions

          The mortality associated with depression increases with the severity of depressive symptoms and is largely independent of comorbid conditions. The use of antidepressants does not reduce the mortality rates of older men with persistent symptoms of depression.

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          Most cited references52

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          Association between obesity and psychiatric disorders in the US adult population.

          Epidemiologic data suggest an association between obesity and depression, but findings vary across studies and suggest a stronger relationship in women than men. To evaluate the relationship between obesity and a range of mood, anxiety, and substance use disorders in the US general population. Cross-sectional epidemiologic survey. Nationally representative sample of US adults. A total of 9125 respondents who provided complete data on psychiatric disorder, height, and weight. Response rate was 70.9%. Participants completed an in-person interview, including assessment of a range of mental disorders (assessed using the World Health Organization Composite International Diagnostic Interview) and height and weight (by self-report). Obesity (defined as body mass index [calculated as weight in kilograms divided by the square of height in meters] of > or =30) was associated with significant increases in lifetime diagnosis of major depression (odds ratio [OR], 1.21; 95% confidence interval [CI], 1.09-1.35), bipolar disorder (OR, 1.47; 95% CI, 1.12-1.93), and panic disorder or agoraphobia (OR, 1.27; 95% CI, 1.01-1.60). Obesity was associated with significantly lower lifetime risk of substance use disorder (OR, 0.78; 95% CI, 0.65-0.93). Subgroup analyses found no difference in these associations between men and women, but the association between obesity and mood disorder was strongest in non-Hispanic whites (OR, 1.38; 95% CI, 1.20-1.59) and college graduates (OR, 1.44; 95% CI, 1.14-1.81). Obesity is associated with an approximately 25% increase in odds of mood and anxiety disorders and an approximately 25% decrease in odds of substance use disorders. Variation across demographic groups suggests that social or cultural factors may moderate or mediate the association between obesity and mood disorder.
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            Effects of exercise training on older patients with major depression.

            Previous observational and interventional studies have suggested that regular physical exercise may be associated with reduced symptoms of depression. However, the extent to which exercise training may reduce depressive symptoms in older patients with major depressive disorder (MDD) has not been systematically evaluated. To assess the effectiveness of an aerobic exercise program compared with standard medication (ie, antidepressants) for treatment of MDD in older patients, we conducted a 16-week randomized controlled trial. One hundred fifty-six men and women with MDD (age, > or = 50 years) were assigned randomly to a program of aerobic exercise, antidepressants (sertraline hydrochloride), or combined exercise and medication. Subjects underwent comprehensive evaluations of depression, including the presence and severity of MDD using Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria and Hamilton Rating Scale for Depression (HAM-D) and Beck Depression Inventory (BDI) scores before and after treatment. Secondary outcome measures included aerobic capacity, life satisfaction, self-esteem, anxiety, and dysfunctional cognitions. After 16 weeks of treatment, the groups did not differ statistically on HAM-D or BDI scores (P = .67); adjustment for baseline levels of depression yielded an essentially identical result. Growth curve models revealed that all groups exhibited statistically and clinically significant reductions on HAM-D and BDI scores. However, patients receiving medication alone exhibited the fastest initial response; among patients receiving combination therapy, those with less severe depressive symptoms initially showed a more rapid response than those with initially more severe depressive symptoms. An exercise training program may be considered an alternative to antidepressants for treatment of depression in older persons. Although antidepressants may facilitate a more rapid initial therapeutic response than exercise, after 16 weeks of treatment exercise was equally effective in reducing depression among patients with MDD.
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              Excess mortality in depression: a meta-analysis of community studies.

              Although most studies examining the relationship between depression and mortality indicate that there is excess mortality in depressed subjects, this is not confirmed in all studies. Furthermore, it has been hypothesized that mortality rates in depressed men are higher than in depressed women. Finally, it is not clear if the increased mortality rates exist only in major depression or also in subclinical depression. A meta-analysis was conducted to examine these questions. A total of 25 studies with 106,628 subjects, of whom 6416 were depressed, were examined. Both univariate and multivariate analyses were conducted. The overall relative risk (RR) of dying in depressed subjects was 1.81 (95% CI: 1.58-2.07) compared to non-depressed subjects. No major differences were found between men and women, although the RR was somewhat larger in men. The RR in subclinical depression was no smaller than the RR in clinical depression. Only RRs of mortality were examined, which were not corrected for important confounding variables, such as chronic illnesses, or life-style. In the selected studies important differences existed between study characteristics and populations. The number of comparisons was relatively small. There is an increased risk of mortality in depression. An important finding of this study is that the increased risk not only exists in major depression, but also in subclinical forms of depression. In many cases, depression should be considered as a life-threatening disorder.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2010
                23 June 2010
                : 5
                : 6
                : e11266
                Affiliations
                [1 ]Western Australia Centre for Health & Ageing, Centre for Medical Research, University of Western Australia, Perth, Western Australia, Australia
                [2 ]School of Psychiatry and Clinical Neurosciences, University of Western Australia, Perth, Western Australia, Australia
                [3 ]Department of Psychiatry, Royal Perth Hospital, Perth, Western Australia, Australia
                [4 ]Stroke Unit, Royal Perth Hospital, Perth, Western Australia, Australia
                [5 ]School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia, Australia
                [6 ]Department of Geriatric Medicine, Royal Perth Hospital, Perth, Western Australia, Australia
                University of Maryland School of Pharmacy, United States of America
                Author notes

                Conceived and designed the experiments: OPA. Performed the experiments: OPA. Analyzed the data: OPA HA. Wrote the paper: OPA HA GJH LF. Obtained funding: OPA GJH LF.

                Article
                10-PONE-RA-16177R1
                10.1371/journal.pone.0011266
                2890408
                20585644
                c3d7c1c0-0dd7-44cc-9f6f-2c871f328ca6
                Almeida et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                History
                : 9 February 2010
                : 2 June 2010
                Page count
                Pages: 9
                Categories
                Research Article
                Geriatrics
                Pharmacology
                Mental Health/Mood Disorders

                Uncategorized
                Uncategorized

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