Treatment-Resistant Late-Life Depression: A Review of Clinical Features, Neuropsychology, Neurobiology, and Treatment

Subha Subramanian; Hanadi A Oughli; Marie Anne Gebara; Ben Julian A Palanca; Eric J Lenze

doi:10.1016/j.psc.2023.02.008

Treatment-Resistant Late-Life Depression: A Review of Clinical Features, Neuropsychology, Neurobiology, and Treatment

Psychiatr Clin North Am. 2023 Jun;46(2):371-389. doi: 10.1016/j.psc.2023.02.008. Epub 2023 Mar 27.

Authors

Subha Subramanian¹, Hanadi A Oughli², Marie Anne Gebara³, Ben Julian A Palanca⁴, Eric J Lenze⁵

Affiliations

¹ Department of Neurology, Berenson-Allen Center for Noninvasive Brain Stimulation, Beth Israel Deaconess Medical Center, Boston, MA, USA; Department of Psychiatry, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA. Electronic address: ssubram5@bidmc.harvard.edu.
² Department of Psychiatry, Semel Institute for Neuroscience, University of California Los Angeles, Los Angeles, CA, USA.
³ Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
⁴ Department of Anesthesiology, Washington University School of Medicine in St. Louis, St Louis, MO, USA; Department of Psychiatry, Washington University School of Medicine in St. Louis, St Louis, MO, USA; Division of Biology and Biomedical Sciences, Washington University School of Medicine in St. Louis; Department of Biomedical Engineering, Washington University in St. Louis, St Louis, MO, USA; Center on Biological Rhythms and Sleep, Washington University School of Medicine in St. Louis, USA; Neuroimaging Labs Research Center, Washington University School of Medicine in St. Louis, St Louis, MO, USA.
⁵ Department of Psychiatry, Washington University School of Medicine in St. Louis, St Louis, MO, USA.

PMID: 37149351
DOI: 10.1016/j.psc.2023.02.008

Abstract

Major depression is common in older adults (≥ 60 years of age), termed late-life depression (LLD). Up to 30% of these patients will have treatment-resistant late-life depression (TRLLD), defined as depression that persists despite two adequate antidepressant trials. TRLLD is challenging for clinicians, given several etiological factors (eg, neurocognitive conditions, medical comorbidities, anxiety, and sleep disruption). Proper assessment and management is critical, as individuals with TRLLD often present in medical settings and suffer from cognitive decline and other marks of accelerated aging. This article serves as an evidence-based guide for medical practitioners who encounter TRLLD in their practice.

Keywords: Diagnosis; Neuromodulation; Neuropsychological factors; Older adults; Presentation; Treatment; Treatment-resistant depression.

Publication types

Case Reports
Review

MeSH terms

Aged
Alzheimer Disease / complications
Anxiety / complications
Depressive Disorder, Treatment-Resistant* / complications
Depressive Disorder, Treatment-Resistant* / diagnosis
Depressive Disorder, Treatment-Resistant* / psychology
Depressive Disorder, Treatment-Resistant* / therapy
Diagnosis, Differential
Electroconvulsive Therapy
Female
Humans
Inflammation / complications
Ketamine
Neuropsychology
Sleep Initiation and Maintenance Disorders / complications
Transcranial Magnetic Stimulation
Vagus Nerve Stimulation

Substances

Esketamine
Ketamine

Grants and funding

R25 MH112473/MH/NIMH NIH HHS/United States