A New Solution to an Age-old Problem: A Review of Ketamine and Esketamine for Treatment-resistant Depression in Late Life

Purpose of Review Treatment-resistant depression in the elderly has been associated with increased disability, hospitalization, functional and cognitive decline, caregiver burden, frailty, healthcare utilization, and overall mortality. Current treatment strategies have significant limitations in this vulnerable population. The purpose of this review is to summarize and report the latest data on the safety and efficacy of ketamine and esketamine in older adults with treatment-resistant major depressive disorder (TRD). Recent Findings Early case report and case series data on the use of ketamine in patients over 65 set the stage for the publication of several recent open label and randomized, blinded clinical trials. While results are variable and not always statistically significant, most trials repeatedly demonstrate antidepressant effect with good safety and tolerability. Summary A preponderance of the recent literature suggest that ketamine and esketamine are safe and well tolerated in older adults. Anti-depressant effects have been repeatedly demonstrated. As might be the case with other antidepressants, some older adults may have a delayed onset of action with ketamine/esketamine beyond the usual 4-week induction period. There may also be evidence to suggest that those with depression onset earlier in life respond better than those with late onset depression and that patients over 75 may have reduced efficacy. The use of these agents in older adults requires additional study to better understand their place in the algorithm for late life depression (especially compared to electroconvulsive therapy), the types of patients most likely to benefit, and potential long term cognitive, urological, or suicide risks. Taken together and in consideration of the degree of disability and suffering caused by late life TRD, the current state of the literature on the use of ketamine and esketamine in older adults supports their place as a viable and safe option within the larger treatment algorithm.