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

Abstract

ContextDepression 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.ObjectiveTo 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.MethodsCohort 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.ResultsThere 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.ConclusionsThe 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.

Associations between the Use of Antidepressants and Other Medications

“…This result confirms previous research where depression was shown to be a risk factor for several chronic conditions (Lépine & Briley, 2011;Centers for Disease Control and Prevention, 2012;Janszky et al, 2007;Clarke & Currie, 2009;Frasure-Smith & Lesperance, 2006;Katon et al, 2007;Almeida, Alfonso, Hankey, & Flicker, 2010;Moussavi et al, 2007;Pratt et al, 1996), and chronic disease, conversely, was shown to be a risk factor for depression (Janszky et al, 2007;Clarke & Currie, 2009;Frasure-Smith & Lesperance, 2006;Katon et al, 2007;Holden et al, 2013;Strine et al, 2008). A large longitudinal study has shown that depression is associated with future health-compromising behaviors (Walsh, Senn, & Carey, 2013), which helps explain increased risk for several chronic conditions that are lifestylerelated.…”

The Mortality and Myocardial Effects of Antidepressants Are Moderated by Preexisting Cardiovascular Disease: A Meta-Analysis

“…One factor contributing to the widespread use of ADs is that they are considered both effective and relatively safe, with mild or rare side effects that are preferred over the debilitating effects of untreated depression. Depression is widely considered a disorder that causes needless suffering [5], and it is associated with an elevated risk of mortality [6,7,8]. People with depression are more likely to suffer from many comorbid physical disorders, such as cardiovascular disease [8,9,10], and they are at elevated risk for suicide [11].…”

“…Thus, while each AD probably has a distinct symptom profile, there is good reason to suspect that they all degrade the functioning of some adaptive processes in the body [3]. Consistent with this hypothesis, several cohort studies of community samples have associated AD use with an elevated risk of cardiovascular events and death, even after controlling for depressive symptoms and other comorbidities [6,7,57]. Although cohort studies cannot conclusively demonstrate causation, randomized controlled trials are often underpowered due to the rarity of death events and the limited duration of follow-up.…”

Are Antidepressants Harmful in the “General Population”?

“…Of the six studies included in the “general population” category, the increased HR was significantly driven by the study by Coupland et al [2], which consisted of patients aged 65–100, hardly being representative of what most would consider the “general population.” The studies by Ryan et al [4] and Almeida et al [5] were also of older adults and Smoller et al [6] exclusively followed postmenopausal women. The only two studies that had samples which would typically be considered the “general population” both failed to show a significant increase in mortality with AD use [7, 8].…”