The New England Journal of MedicineTreatment-Resistant Depression in Older Adults

A case vignette highlighting a common clinical problem, followed by evidence supporting various strategies.

The prevalence and challenge of managing treatment-resistant depression (TRD) in older adults are significant, underscored by the biopsychosocial intricacies that influence diagnosis and treatment outcomes. This article offers a comprehensive overview of the current understanding and management strategies for TRD among the elderly, highlighting the importance of personalized, multi-modal approaches. Through a detailed case vignette and a synthesis of evidence-based practices, it provides critical insights into the factors contributing to TRD, assessment techniques, and therapeutic interventions aimed at improving patient outcomes.

Key Points:

• Treatment-resistant depression is prevalent in older adults and is influenced by various factors, including chronic medical conditions, cerebrovascular disease, coexisting anxiety, chronic dysthymia, substance abuse, and bereavement.
• A commonly accepted definition of TRD is the lack of improvement despite adequate trials of two different classes of antidepressants for at least 8 weeks.
• Assessment should include screening for coexisting medical and psychiatric conditions, using validated tools like the Patient Health Questionnaire (PHQ-9) and the Geriatric Depression Scale.
• Management strategies involve measurement-based collaborative care, with a focus on continuous monitoring and adjustment of treatment until remission is achieved.
• Pharmacological augmentation strategies include the use of second-generation antipsychotic agents, lithium, or another antidepressant, while considering the specific needs and potential side effects in older adults.
• Referral for psychiatric evaluation is recommended for patients with severe depression, worsening suicidal ideation, psychosis, or coexisting cognitive impairment, for considerations such as electroconvulsive therapy (ECT) or other advanced treatments.
• Psychotherapy remains a cornerstone for the treatment of mild-to-moderate TRD, with cognitive behavioral therapy, problem-solving therapy, and interpersonal therapy being effective options.
• Evidence base for pharmacological treatment of TRD in older adults is limited but includes strategies like switching antidepressants or augmentation with other agents.
• Somatic treatments like ECT, transcranial magnetic stimulation (TMS), and ketamine or esketamine therapy are valuable for severe TRD cases not responding to medication and psychotherapy.

According to this article, the prevalence of depression among older adults in community settings can be as high as 13.5%, yet it often remains underdiagnosed and undertreated.

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