Antidepressants May Not Be Enough When Frailty Complicates Depression in Late Life

Brown et al.’s paper in this issue of the Journal expands upon the authors’ prior work on the frailty-depression phenotype to examine the impact of physical frailty on 8 weeks of antidepressant treatment among 100 adults aged 60 and over with major depression. Almost half the participants met the author's definition of frailty but did not differ from the rest on measures of medical co-morbidity, demography, depression severity, and cognitive performance. All were followed for 10 months of open-label pharmacotherapy after the initial 8 weeks of double-blind, randomized intervention. Because criteria for both frailty and depression such as fatigue, slowed physical activity, and weight loss overlap, the authors needed to statistically correct for a potential specious relationship. Of the frailty measures, only lessor physical activity and weaker grip strength were associated with attenuated response to antidepressant treatment. Executive dysfunction, a predictor of inadequate response to antidepressant therapy was not individually measured but the participants reported on average 16 years of education and scored well into the unimpaired range (27–30 points) on the Mini Mental State Exam. Similarly, most participants reported the first depressive episode in their late 30s in which executive dysfunction is less prevalent than episodes beginning after age 55. The finding that a threshold of elevations in three or more of the five frailty criteria was associated with attenuated response suggests it may be used, like executive dysfunction as a response predictor and an indicator of the need from more than an antidepressant. This is similar to findings that neural network connectivity and varying interactions between nodes of the networks predict treatment response and may dictate the choice of psychotherapy or pharmacotherapy. ^,