Frailty and Depression in Late Life: A High-Risk Comorbidity With Distinctive Clinical Presentation and Poor Antidepressant Response

Abstract

Background Investigate the longitudinal relationship between physical frailty, the clinical representation of accelerated biological aging, and antidepressant medication response in older adults with depressive illness. Methods An 8-week randomized placebo-controlled trial (escitalopram or duloxetine) followed by 10-months of open antidepressant medication treatment (augmentation, switch strategies) was conducted in an outpatient research clinic. 121 adults age > 60 years with Major Depressive (MDD) or Persistent Depressive Disorders and a 24-item Hamilton Rating Scale for Depression (HRSD) > 16 were enrolled. Primary measures assessed serially over 12-months include response (50% reduction from baseline HRSD score), remission (HRSD score < 10), and frailty (non/intermediate frail [0-2 deficits] vs frail [> 3 deficits]); latent class analysis was used to classify longitudinal frailty trajectories. Results A 2-class model best fit the data, identifying a consistently-low frailty-risk (63% of the sample) and consistently-high frailty-risk (37% of the sample) trajectory. Response and remission rates (P’s<.002) for adults in the high-risk frailty class were at least 21 percentage-points worse than those in the low-risk class over 12-months. Furthermore, subsequent frailty was associated with previous frailty (P’s < .01) but not previous response or remission (P’s > .10). Conclusions Antidepressant medication is poorly effective for MDD occurring in the context of frailty in older adults. Furthermore, even when an antidepressant response is achieved, this response does little to improve their frailty. These data suggest that standard psychiatric assessment of depressed older adults should include frailty measures and that novel therapeutic strategies to address comorbid frailty and depression are needed.

Predictive value of frailty in the mortality of hospitalized patients with COVID-19: a systematic review and meta-analysis

“…There are several well-validated frailty assessment tools used for screening and quantifying frailty status. Many studies across different diseases have revealed that frailty is associated with a variety of poor health outcomes, such as falls, dementia, mortality, hospitalization, and poor quality of life (39)(40)(41). As such, it is important to evaluate frailty status comprehensively to optimize outcomes.…”

Association of Molecular Senescence Markers in Late-Life Depression With Clinical Characteristics and Treatment Outcome

“…A recent meta-analysis 3 identified higher baseline depression severity, comorbid anxiety, and executive dysfunction as the most important clinical variables associated with poor treatment response in LLD. Other studies 4 , 5 , 6 , 7 have also identified cardiovascular risk factors (eg, metabolic syndrome), cerebrovascular disease, brain structural changes, physical comorbidity, and frailty as variables associated with poor treatment response. Some of these variables are common in depression across the lifespan (eg, comorbid anxiety and depression severity), but others are geriatric specific (eg, cerebrovascular disease burden and executive dysfunction), suggesting that remission with treatment in LLD may have specific mechanisms that are associated with age-related brain and systemic aging processes.…”

Associations of poor sleep quality, chronic pain and depressive symptoms with frailty in older patients: is there a sex difference?

“…Thus, our study excluded patients with clinically diagnosed depressive or anxiety disorders who were taking antidepressants in order to avoid confounding the observed associations. Another study also found that frailty itself, in turn, worsened antidepressant treatment responses and outcomes [ 52 , 53 ]. Furthermore, chronic pain, as the origin of various health hazards, was closely associated with comorbidities such as depression and sleep disorders, and further contributed to frailty and increased adverse outcomes among older adults [ 54 ].…”