The Frail Depressed Patient: A Narrative Review on Treatment Challenges

Abstract

Although the public importance of frailty is widely acknowledged by the World Health Organization, physical frailty is still largely neglected in geriatric mental health care. Firstly in this narrative review, we summarize the knowledge on the epidemiology of the association between depression and frailty, whereafter implications for treatment will be discussed. Even though frailty and depression have overlapping diagnostic criteria, epidemiological studies provide evidence for distinct constructs which are bidirectionally associated. Among depressed patients, frailty has predictive validity being associated with increased mortality rates and an exponentially higher fall risk due to antidepressants. Nonetheless, guidelines on the treatment of depression neither consider frailty for risk stratification nor for treatment selection. We argue that frailty assessment enables clinicians to better target the pharmacological and psychological treatment of depression as well as the need for interventions targeting primarily frailty, for instance, lifestyle interventions and reduction of polypharmacy. Applying a frailty informed framework of depression treatment studies included in a meta-analysis reveals that the benefit–harm ratio of antidepressants given to frail depressed patients can be questioned. Nonetheless, frail-depressed patients should not withhold antidepressants as formal studies are not available yet, but potential adverse effects should be closely monitored. Dopaminergic antidepressants might be preferable when slowness is a prominent clinical feature. Psychotherapy is an important alternative for pharmacological treatment, especially psychotherapeutic approaches within the movement of positive psychology, but this approach needs further study. Finally, geriatric rehabilitation, including physical exercise and nutritional advice, should also be considered. In this regard, targeting ageing-related abnormalities underlying frailty that may also be involved in late-life depression such as low-grade inflammation might be a promising target for future studies. The lack of treatment studies precludes firm recommendations, but more awareness for frailty in mental health care will open a plethora of alternative treatment options to be considered.

Prevalence of Frailty and Its Association with Depressive Symptoms among European Older Adults from 17 Countries: A 5-Year Longitudinal Study

“…Moreover, frailty interventions should focus on promoting social relationships and improving parameters of physical independence, which may contribute to dealing with depressive symptoms. A recent narrative review highlights the importance of a multidisciplinary treatment for frail patients with depression, including physical exercise and nutritional advice [ 16 ].…”

“…The overlap of frailty and depression syndromes has been studied, and a positive association between the two has been found [ 12 , 13 , 14 ]. Therefore, the literature suggests that depression and frailty are interrelated concepts but distinct constructs that are bidirectionally associated [ 15 , 16 ]. Several explanations have been offered for these associations.…”

“…Moreover, the two syndromes could share similar symptoms and risk factors, such as fatigue, loss of weight, poor physical activity, and cognitive impairment [ 18 , 19 ]. Furthermore, the two conditions share similar pathophysiological mechanisms, such as inflammation, immunometabolic dysregulation, dopamine depletion, and mitochondrial dysfunction [ 16 , 20 , 21 ].…”

“…However, such studies are limited, and their findings are controversial. A recent review of six longitudinal studies analyzed frailty as a predictor of depression [ 16 ]. Among these studies, five found that frailty was associated with depressive symptoms [ 22 , 23 , 24 , 25 , 26 ], while one did not find this association.…”

Exploring human biology with N-of-1 clinical trials

“…There are many settings beyond multimorbidity issues that justify an evaluation of multiple health measures in N-of-1 clinical trials. For example, depression is known to impact virtually all aspects of a person’s health due to the various behaviors adopted by depressed individuals (Triolo et al, 2020 ; Aprahamian et al, 2022 ). Testing the effect of an antidepressant on mood and depressive symptoms in addition to, perhaps, weight, blood pressure, sleep quality, etc.…”