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
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to The American Journal of Geriatric PsychiatryAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- A tune in "a minor" can "b major": a review of epidemiology, illness course, and public health implications of subthreshold depression in older adults.J Affect Disord. 2011; 129: 126-142
- Predicting remission in late-life major depression: a clinical algorithm based upon past treatment history.J Clin Psychiatry. 2019; 80: e1-e7
- Antidepressant medication and executive dysfunction: a deleterious interaction in late-life depression.Am J Geriatr Psychiatry. 2010; 18: 128-135
- Predictors of recurrence in remitted late-life depression.Depress Anxiety. 2018; 35: 658-667
- STAR*D: revising conventional wisdom.CNS Drugs. 2009; 23: 627-647
- Biological aging and the future of geriatric psychiatry.J Gerontol A Biol Sci Med Sci. 2017; 72: 343-352
- Research domain criteria: toward future psychiatric nosologies.Dialogues Clin Neurosci. 2015; 17: 89-97
- Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression.Biol Psychiatry. 2009; 65: 732-741
- Inflammation, depression, and slow gait: a high mortality phenotype in later life.J Gerontol A Biol Sci Med Sci. 2016; 71: 221-227
- Frailty and depression in older adults: a high-risk clinical population.Am J Geriatr Psychiatry. 2014; 22: 1083-1095
- Frailty and its correlates in adults with late life depression.Am J Geriatr Psychiatry. 2020; 28: 145-154
- The depressed frail phenotype: the clinical manifestation of increased biological aging.Am J Geriatr Psychiatry. 2016; 24: 1084-1094
- Development of a rating scale for primary depressive illness.Br J Soc Clin Psychol. 1967; 6: 278-296
- Gait speed and survival in older adults.JAMA. 2011; 305: 50-58
- The CES-D scale: a self-report depression scale for research in the general population.Appl Psychol Meas. 1977; 1: 385-401
- Frailty in older adults: evidence for a phenotype.J Gerontol A Biol Sci Med Sci. 2001; 56: M146-M156
- Measuring disability across cultures–the psychometric properties of the WHODAS II in older people from seven low- and middle-income countries. the 10/66 dementia research group population-based survey.Int J Methods Psychiatr Res. 2010; 19: 1-17
- Statistical Analysis With Missing Data, Third Edition.Wiley, 2019
- A note on marginalization of regression parameters from mixed models of binary outcomes.Biometrics. 2018; 74: 354-361
- R: A Language and Environment for Statistical Computing. 2020;
- GLMMadaptive: Generalized Linear Mixed Models Using Adaptive Gaussian Quadrature. R Package Version 0.6-8.2020
- Fitting linear mixed-effects models using lme4.J Stat Softw. 2015; 67: 1-48
- Depression and frailty: the need for multidisciplinary research.Am J Geriatr Psychiatry. 2004; 12: 1-6
- Relationship between depression and frailty in older adults: a systematic review and meta-analysis.Ageing Res Rev. 2017; 36: 78-87
- Frailty in older adults: evidence for a phenotype.J Gerontol A Biol Sci Med Sci. 2001; 56: M146-M156
- Respirometric profiling of muscle mitochondria and blood cells are associated with differences in gait speed among community-dwelling older adults.J Gerontol A Biol Sci Med Sci. 2015; 70: 1394-1399
- Skeletal muscle mitochondrial energetics are associated with maximal aerobic capacity and walking speed in older adults.J Gerontol A Biol Sci Med Sci. 2013; 68: 447-455
- Skeletal muscle mitochondrial function and fatigability in older adults.J Gerontol A Biol Sci Med Sci. 2015; 70: 1379-1385
- Declining skeletal muscle mitochondrial function associated with increased risk of depression in later life.Am J Geriatr Psychiatry. 2019; 27: 963-971
- Mitochondrial respiration in peripheral blood mononuclear cells correlates with depressive subsymptoms and severity of major depression.Transl Psychiatry. 2014; 4: e397
- The many roads to mitochondrial dysfunction in neuroimmune and neuropsychiatric disorders.BMC Med. 2015; 13: 68
- Skeletal muscle mitochondria in the elderly: effects of physical fitness and exercise training.J Clin Endocrinol Metab. 2014; 99: 1852-1861
- Effects of a physical activity intervention on measures of physical performance: results of the lifestyle interventions and independence for Elders Pilot (LIFE-P) study.J Gerontol A Biol Sci Med Sci. 2006; 61: 1157-1165
- Marked disparity between age-related changes in dopamine and other presynaptic dopaminergic markers in human striatum.J Neurochem. 2003; 87: 574-585
- Effects of L-DOPA monotherapy on psychomotor speed and [(11)C]raclopride binding in high-risk older adults with depression.Biol Psychiatry. 2019; 86: 221-229
- Inflammation and stress-related candidate genes, plasma interleukin-6 levels, and longevity in older adults.Exp Gerontol. 2009; 44: 350-355
- Inflammaging and anti-inflammaging: a systemic perspective on aging and longevity emerged from studies in humans.Mech Ageing Dev. 2007; 128: 92-105
- Relationship of interleukin-6 and tumor necrosis factor-alpha with muscle mass and muscle strength in elderly men and women: the Health ABC Study.J Gerontol A Biol Sci Med Sci. 2002; 57: M326-M332
- A randomized controlled trial of the tumor necrosis factor antagonist infliximab for treatment-resistant depression: the role of baseline inflammatory biomarkers.JAMA Psychiatry. 2013; 70: 31-41
- Anti-inflammatory treatment of depression: study protocol for a randomised controlled trial of vortioxetine augmented with celecoxib or placebo.Trials. 2018; 19: 447
Article info
Publication history
Published online: December 24, 2020
Accepted:
December 21,
2020
Received in revised form:
December 8,
2020
Received:
October 29,
2020
Identification
Copyright
© 2020 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.
