Antidepressants in Older Adults: Complexities, Confounds and Clinical Effects

Abstract

lder adults with depression are often treated with antidepressant medications, but there is only limited evidence from controlled trials to sup- port their efficacy. The high frequency and severity of concurrent illness and medications in older adults with depression often makes the risk-benefit ratio difficult to calculate. Several reports in this issue are relevant to this ongoing dialectic, both in depressed patients without significant cognitive impairment and in patients with dementing illnesses who mani- fest depressive symptomatology. heimer disease (AD) and dementia with Lewy bodies, depression was associated with cortical thinning in prefrontal and temporal areas, and antidepressant use was associated with thinning in the parahippocampal region. The cross-sectional study design makes it difficult to infer cause and effect, and it remains unclear if cortical thinning preceded the onset of depression in dementia or whether the use of antide- pressants contributed to parahippocampal thinning. Theauthorssuggestthatdepressivesymptomsinmild dementiacandevelopduetoneurodegenerationinthe same neural circuits that are compromised in late life depression more broadly. In late-life depression without dementia, antidepressant treatment response has been shown to be lower in patients with smaller hippocampal volumes and impaired cognitive func- tioning, 2 consistent with the view that neurodegener- ative processes underlie depression in many elderly patients and that antidepressant treatment is less effective in these patients. Further, frontal-striatal- limbic circuits have been postulated to be involved in the pathogenesis of late life depression, and cere- brovascular causes have been implicated. 3 Although thereisextensivedegenerationofcatecholaminenergic neurons in the brain in AD, 4 selective serotonin reup- take inhibitors (SSRIs) have shown limited efficacy for depression in AD as discussed in a meta-analysis of antidepressant treatment for depression in dementia. 5