NEIFG 005 Obligaciones laborales

The impact of depression upon health related outcome is tangible. In a recent study of HD patients, depression symptoms were associated with significantly more hospital admissions and emergency department visits (Tavallaii, Ebrahimnia, Shamspour, & Assari, 2009). In the general population depression is associated with increased mortality risk (Wulsin, Vaillant,

& Wells, 1999), although methodological issues confound certain studies. A recent study investigated the impact of depression and anxiety symptoms using the Hospital Anxiety and Depression Scale (HADS) upon mortality in a large population survey (Mykletun et al., 2009). In a comprehensive analysis, the authors were able to demonstrate a significant effect of depressive symptoms upon survival after controlling for several factors including somatic conditions, physical activity and smoking status (OR=1.37, 95% CI 1.19 to 1.58).

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Interestingly the adjustment of somatic conditions led to an attenuation of the depression-mortality association. Physical illness is therefore an important confound in this context, and suggests further the intimate relationship between depression and physical illness.

Cardiovascular disease (CVD) is a prominent co-morbidity among the dialysis population and one of the largest contributors of mortality (see chapter 1). There is also a comprehensive literature linking depression with CVD (Steptoe, 2007). Pro-inflammatory cytokines appear to be heightened in HD patients and predict mortality (Kimmel, Phillips et al., 1998). There is evidence that depression is associated with these cytokines including IL-6, IL-1β and TNF-α and CRP in both the general and ESRD populations (Appels, Bar, Bar, Bruggeman, & de Baets, 2000; Kop et al., 2002; Miller, Stetler, Carney, Freedland, & Banks, 2002; Simic Ogrizovic et al., 2009; Suarez, 2003). In a recent study, ESRD patients with a BDI≥14, had significantly higher IL-6 and hsCRP as compared to those with a BDI<14 (Simic Ogrizovic et al., 2009). Pro-inflammatory markers are associated in the pathogenesis of CVD (Ridker, Rifai, Rose, Buring, & Cook, 2002). It is proposed that immune functioning and inflammation mediates the link between depression and CVD (Lesperance, Frasure-Smith, Theroux, & Irwin, 2004). Efforts to investigate the complex pathways between depression, immune parameters and CVD in ESRD patients seem highly relevant particularly as CVD and depression remain prominent co-morbidities among HD patients. In addition, research has shown associations between depressive affect and malnutrition in ESRD patients (Koo et al., 2003), although the related causality remains unknown. There is evidence of the association between malnutrition, inflammation, and atherosclerosis (MIA) in ESRD patients (Honda et al., 2006; Wang et al., 2004); some have suggested that depression could be involved in MIA syndrome (Simic Ogrizovic et al., 2009), albeit with a great need for further investigation.

Although detailed description of the behavioural and pathological mechanisms underlying depression and mortality is beyond the scope of this chapter, there is evidence linking depression and mortality among the ESRD population (Boulware et al., 2006; Drayer et al., 2006; Einwohner, Bernardini, Fried, & Piraino, 2004; Hedayati et al., 2008; Kimmel et al., 2000; Lopes et al., 2004; Lopes et al., 2002; Shulman, Price, & Spinelli, 1989), including those withdrawing from dialysis (Lopes et al., 2004; McDade-Montez, Christensen,

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Cvengros, & Lawton, 2006). A summary of this literature is presented in table 2.2. It should be noted that while a depression-mortality association is well established, the association between depression and withdrawal may be confounded by the fact that depression symptoms are likely to increase the nearer to death. Depressive symptoms (BDI≥11) have also been found to predicted peritonitis in a study of 162 PD patients after controlling for age, diabetes, race and coronary artery disease (hazard ratio= 2.7, 95% CI 1.23 and 6.03).

However whether this was due to diminished health care behaviour or impaired immunological function is not known (Troidle et al., 2003). Furthermore given the current evidence regarding suitable BDI cut-off scores in ESRD, a BDI ≥11 may be considered too low as these scores requirement adjust in this patient group (Grant et al., 2008).

It is important to note, that while most outcome studies control for variates such as co-morbidity and age, studies differ with regards to the measurement of depression (symptom severity vs. diagnostic) and analytic techniques (time varying models, vs. fixed baseline models). Indeed, some studies have reported null findings with regards to any association between depression and mortality in ESRD patients (Christensen, Wiebe, Smith, & Turner, 1994; Devins et al., 1990). Kimmel et al (2000) investigated the association between depression and mortality in 295 HD patients using the BDI and CDI. In adjusted models baseline depression scores failed to predict mortality. However in time-varying models, both the BDI and CDI predicted mortality after controlling for a range of clinical parameters (table 2.2). Bowlware et al (2006) investigated the relationship between depressive symptoms, cardiovascular events and mortality. Time varying models demonstrated that symptoms of depression were associated with increased all cause mortality and cardiovascular events at a 2 year follow-up, whereas baseline measures did not. This association was attenuated, however, after a 6-month time lag was incorporated into the analysis. This suggests that deteriorating co-morbidity may at least partially explain the association between depression and mortality rather than depression worsening morbidity.

Both Kimmel et al (2000) and Boulware et al (2006) employed depression screening tools to assess depressive symptoms. In the case of the latter study, depression was assessed using a non-conventional approach (subscale from the Medical Outcomes Study Short Form-36 questionnaire).

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Recently the association between a formal diagnosis of clinical depression and mortality has been established (Hedayati et al., 2008). Ninety eight HD patients were assessed using the SCID, which identified 26 as suffering from depressive disorder. Differences between the depressed (as diagnosed via the SCID) and non-depressed revealed a greater prevalence of co-morbidity in the depressed. In multivariate analysis after controlling for age, ethnicity, gender, time of dialysis and co-morbidity, a diagnosis of depression was significantly associated with mortality. Interestingly, self-report measures were not significant predictors of mortality in sub-analysis.

In summary there is considerable evidence regarding the association between depression and mortality in ESRD patients. While further research is required to better understand this relationship, it is also important to establish the utility of treating depression upon patient outcome of which the current evidence is mixed (Detweiler-Bedell, Friedman, Leventhal, Miller, & Leventhal, 2008).