The SSRIs may be too nonspecific and “broadspectrum” to hope for significant cognitive benefits in late-life anxiety treatment. There have been no prospective studies of serotonin norepinephrine reuptake inhibitors (SNRIs) specifically in late-life anxiety as there have in late-life depression. A retrospective examination of phase 3 venlafaxine XR data found the drug to be efficacious in adults aged 60+, with an effect size (drug-placebo difference) and side-effect profile
similar to younger adults.165 Similar findings have been reported with duloxetine.166 These studies in SSRIs and SNRIs have found similar side effects in elderly persons Inhibitors,research,lifescience,medical as in younger adults, but importantly they were not designed to determine the recently reported potential risks of SSRIs specific to the elderly population: gait impairment increasing risk for falls,167 and bone loss.168 Inhibitors,research,lifescience,medical Other risks that are greater in older adults
are impaired clotting leading to non-GI and GI bleeding169 and SIADII leading to hyponatremia.170 Such reports suggest that the risk:benefit ratio for longterm SSRI/SNRI use is not the same as in younger adults. These concerns have yet to be addressed in a properly constructed longitudinal study (ie, a randomized controlled trial with an adequate safety evaluation). In terms of non-SSRI/SNRI treatments, a large-scale study with pregabalin in geriatric GAD showed efficacy.171 Pregabalin Inhibitors,research,lifescience,medical is not FDA-approved to treat anxietydisorders; its mechanism of action for anxiety is unknown – it binds to an auxiliary subunit voltage-gated
calcium channels and is thought to reduce the synaptic release of several neurotransmitters. Mirtazapine is another non-SSRI/SNRI treatment with efficacy in anxiety, with some evidence Inhibitors,research,lifescience,medical specifically in late-life anxiety disorders.172 Most geriatric anxiety pharmacotherapy research has focused on GAD. There has been one promising study of the SSRI citalopram in older adults with PTSD,173 and also evidence that the α-adrenergic antagonist prazosin is efficacious for sleep-related concerns in PTSD, although Inhibitors,research,lifescience,medical not for other PTSD symptoms.174 There are two small studies in late-life panic disorder: Rampello et al175 found superiority of escitalopram over citalopram in time to response, and a small open-label study Entinostat found promising signals with sertraline.176 Finally, in GAD in the context of stroke, one analysis found efficacy of nortriptyline in a merged dataset of several RCTs of post-stroke depression, in which patients with comorbid GAD were analyzed.177 The only published Calcitriol IL-2 augmentation study in late-life anxiety disorders is a small study with risperidone.178 While the atypical antipsychotic was promising, there have been concerns with atypicals in older adults, given evidence of higher mortality with antipsychotics in older patients with dementia, and metabolic effects including weight gain, elevated lipids, and insulin resistance.