A Review of Therapeutics for Treatment-Resistant Depression in the Older Adult

One-third of older adults with depression meet criteria for treatment resistance, typically defined as a lack of response to two or more adequate trials of an antidepressant. Treatment resistance contributes to an unfavorable prognosis, compromised medical outcomes, heightened disability, accelerated cognitive decline, and an elevated risk of developing dementia. Despite this significant morbidity, evidence is sparse for how to proceed with treatment in this population. Non-pharmacologic therapy (e.g., diet, psychotherapy) can be utilized as adjunctive therapy, despite little published evidence of benefit, given that the risks are low. Pharmacotherapy trials in the treatment-resistant late-life depression population lack strong methods and external validity; however, the use of venlafaxine as monotherapy and add-on therapy, as well as lithium, bupropion, or aripiprazole as add-on therapy to standard antidepressant therapy, have enough evidence that a trial with appropriate monitoring is a prudent strategy. Electroconvulsive therapy remains a well-studied safe therapy, especially when used as maintenance treatment once an initial cycle is completed but is traditionally underutilized in the treatment-resistant late-life depression population. Ensuring non-pharmacologic and pharmacologic strategies are optimized and given a sufficient trial in those with treatment-resistant late-life depression is the best we can do for this vulnerable population.