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Frailty Worsens Antidepressant Treatment Outcomes in Late Life Depression

Published:December 24, 2020DOI:https://doi.org/10.1016/j.jagp.2020.12.024

      Highlights

      • What is the primary question addressed in this study?
        Adults with late life depression are worse than nondepressed older adults on all five characteristics of the biological syndrome of frailty: they display lower physical activity levels, a greater prevalence of fatigue and significant weight loss, slower gait speeds, and weaker grip strength. Frailty in adults with late life depression results in increased mortality risk. Whether frailty burden predicts who will or will not respond to antidepressant medication, however, remains unknown. As such, the primary focus of this study was to investigate the relationship between frailty and treatment response to antidepressant medications in adults with late life depression.
      • What is the main finding of this study?
        The main findings from this study are that greater frailty burden and specific characteristics including weak grip strength and low physical activity levels are associated with an attenuated response to antidepressant medications and a greater degree of disability compared with nonfrail adults with LLD, even after receiving a greater number of antidepressant medications.
      • What is the meaning of the finding?
        This study provides evidence that frailty may identify a high-risk subgroup of late life depression defined by lower antidepressant response to medication treatments, greater disability, and higher mortality risk. Future research must focus on understanding the specific pathophysiology associated with the frail-depressed phenotype to permit the design and implementation of precision medicine interventions for this high-risk population.

      Abstract

      Objective

      To investigate the relationship between frailty and treatment response to antidepressant medications in adults with late life depression (LLD).

      Methods

      Data were evaluated from 100 individuals over age 60 years (34 men, 66 women) with a depressive diagnosis, who were assessed for frailty at baseline (characteristics include gait speed, grip strength, activity levels, fatigue, and weight loss) and enrolled in an 8-week trial of antidepressant medication followed by 10 months of open-treatment.

      Results

      Frail individuals (n = 49 with ≥3 deficits in frailty characteristics) did not differ at baseline from the non/intermediate frail (n = 51 with 0–2 deficits) on demographic, medical comorbidity, cognitive, or depression variables. On average, frail individuals experienced 2.82 fewer Hamilton Rating Scale for Depression (HRSD) points of improvement (t = 2.12, df 89, p = 0.037) than the non/intermediate frail over acute treatment, with this difference persisting over 10 months of open-treatment. Weak grip strength and low physical activity levels were each associated with decreased HRSD improvement, and lower response and remission rates over the course of the study. Despite their poorer outcomes, frail individuals received more antidepressant medication trials than the non/intermediate frail.

      Conclusion

      Adults with LLD and frailty have an attenuated response to antidepressant medication and a greater degree of disability compared to non/intermediate frail individuals. This disability and attenuated response remain even after receiving a greater number of antidepressant medication trials. Future research must focus on understanding the specific pathophysiology associated with the frail-depressed phenotype to permit the design and implementation of precision medicine interventions for this high-risk population.

      Key Words

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