The Efficacy of Antidepressants in the Treatment of Late-Life Depression

Department of Psychiatry, College of Physicians and Surgeons, Columbia University, 1051 Riverside Drive, New York, NY 10032, USA.
Journal of Clinical Psychopharmacology (Impact Factor: 3.24). 09/2005; 25(4 Suppl 1):S1-7. DOI: 10.1097/
Source: PubMed


This review addresses the question of whether there is evidence that antidepressants are more efficacious than placebo in the treatment of late-life depression and what is the rate of response that physician and patient can expect when antidepressant medication is prescribed in a typical clinical setting. To date, 5 placebo-controlled and 10 comparison trials have study designs of sufficient rigor to provide evidence of antidepressant efficacy and effectiveness in the treatment of late-life depression. The results suggest that antidepressant medications are more effective than placebo. However, placebo-controlled trials are not a simple comparison of only medication versus placebo. Rather, the amount of nonspecific psychosocial interventions included in these trials is considerable and often not systematically measured. Trial design also affects outcome: response and remission rates in comparison trials consistently are 20% to 30% higher than those reported in placebo-controlled trials. Clinical trials do not consistently assess the many moderators that are believed to affect treatment outcome in late-life depression, and therefore, comparisons across studies are problematic because of an inability to determine whether patient samples are truly comparable. For future clinical trials to have maximal relevance, study design should evolve to reflect as closely as possible a typical clinical setting especially with respect to frequency and duration of patient visits.

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    • "Major depressive disorder (MDD) is a major public health concern with a lifetime prevalence of 17% in the United States and a leading cause of disability worldwide (Kessler et al., 2005;Moussavi et al., 2007). Up to 65% of those who suffer from a major depressive episode will have recurrent episodes (Eaton et al., 2008;Yiend et al., 2009), and only about a third of adults with MDD are successfully treated with initial therapies (Alexopoulos, 2005;Roose and Schatzberg, 2005). A potential reason for therapeutic failure is that dysfunction in MDD is not restricted to the brain. "
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    ABSTRACT: Major depressive disorder (MDD) is one of the most prevalent major psychiatric disorders with a lifetime prevalence of 17%. Recent evidence suggests MDD is not only a brain dysfunction, but a systemic disease affecting the whole body. Central and peripheral inflammatory changes seem to be a centerpiece of MDD pathology: a subset of patients show elevated blood cytokine and chemokine levels that partially normalize with symptom improvement over the course of anti-depressant treatment. As this inflammatory process in MDD is poorly understood, we hypothesized that the peripheral tissues of MDD patients will respond differently to inflammatory stimuli, resulting in an aberrant transcriptional response to elevated pro-inflammatory cytokines. To test this, we used MDD patient- and control-derived dermal fibroblast cultures to investigate their response to an acute treatment with IL6, IL1β, TNFα, or vehicle. Following RNA isolation and subsequent cDNA synthesis, quantitative PCR was used to determine the relative expression level of several families of inflammation-responsive genes. Our results showed comparable expression of the tested genes between MDD patients and controls at baseline. In contrast, MDD patient fibroblasts had a diminished transcriptional response to IL6 in all the gene sets tested (oxidative stress response, mitochondrial function, and lipid metabolism). We also found a significant increase in baseline and IL6 stimulated transcript levels of the IL6 receptor gene. This IL6 receptor transcript increase in MDD fibroblasts was accompanied by an IL6 stimulated increase in induction of SOCS3, which dampens IL6 receptor signaling. Altogether our results demonstrate that there is an altered transcriptional response to IL6 in MDD, which may represent one of the molecular mechanisms contributing to disease pathophysiology. Ultimately we hope that these studies will lead to validation of novel MDD drug targets focused on normalizing the altered IL6 response in patients.
    Full-text · Article · Jan 2016 · Neurobiology of Disease
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    • "In many efficacy trials of antidepressants in the treatment of late-life depression, antidepressants were more effective than placebos, and no difference was found in antidepressant class outcomes among older adults with major depression or nonspecific depression severity, although SSRIs may be better tolerated than tricyclics (Roose and Schatzberg 2005; Reynolds et al. 2006). However, a meta-analysis of the use of second-generation antidepressants in late life found their effects tend to be modest (Nelson et al. 2008). "
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    ABSTRACT: Little research has been done on the use of antidepressants among homebound older adults, especially low-income homebound older adults, and their perceptions of the effectiveness of their medication. The purposes of this study were to examine self-reported use of antidepressants among depressed homebound older adults, class and type of antidepressants used, individual-level correlates of antidepressant use, and users' perceptions of the effectiveness of antidepressants. Data on self-reported use of antidepressants were obtained as part of a feasibility study of short-term telehealth problem-solving therapy for depressed low-income homebound adults (n = 162) aged 50 or older. The 24-item Hamilton Rating Scale for Depression (HAMD) was used to assess depression severity. The findings show that about half of the study participants were taking antidepressants, with 26.6% of those on antidepressants rating their medications very effective and 21.5% rating them effective. Female gender was positively, but older age and being Black/African American were negatively associated with the likelihood of antidepressant use. Perceived effectiveness of antidepressants was negatively associated with older age and the HAMD score. The findings suggest that personalized approaches to depression management may be needed in subgroups of depressed older adults, including culturally tailored medication counseling in Black/African-American older adults.
    Full-text · Article · Mar 2012 · Brain and Behavior
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    • "Clinically, it could be suggested that the data may imply that serotonergic drugs may be less likely to be effective in depression in the elderly. However, there is little evidence that this is the case (Roose and Schatzberg, 2005). Our previous report (Mace et al., 2010) examined the effects of ATD on mood in PD and healthy controls and included data from a number of the healthy controls in the current study. "
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    ABSTRACT: Few studies have investigated the function of the serotonin (5-HT) system in the elderly. Previous studies have shown effects of reducing serotonin function, by acute tryptophan depletion (ATD), on neuropsychological function in healthy subjects but this technique has not previously been employed over a wide age range in the elderly. This study compared the effects of ATD on mood, cognitive function and motor function in two groups of healthy volunteers, one group aged 50-69 and the other aged 70-89. The effects of ATD were investigated in a double-blind, placebo-controlled, counterbalanced, crossover, randomized design. The effects of ATD were not significantly different between age groups, suggesting that there is relatively little functional change across these age ranges. Compared with studies in much younger age groups there was, however, more evidence of an adverse effect of ATD on psychomotor function and working memory. There was no effect of ATD on mood despite inclusion of subjects with a family history of depression.
    Full-text · Article · Dec 2011 · Journal of Psychopharmacology
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