Intravenous Ketamine for Late-Life Treatment-Resistant Depression: A Pilot Study of Tolerability, Safety, Clinical Benefits, and Effect on Cognition

• Published in: The American journal of geriatric psychiatry 2023-03, Vol.31 (3), p.210-221
• Main Authors: Oughli, Hanadi Ajam, Gebara, Marie Anne, Ciarleglio, Adam, Lavretsky, Helen, Brown, Patrick J., Flint, Alastair J., Farber, Nuri B., Karp, Jordan F., Mulsant, Benoit H., Reynolds, Charles F., Roose, Steven P., Yang, Lei, Butters, Meryl A., Lenze, Eric J.
• Format: Article
• Language: English
• Subjects: Aged; Cognition; Depression; geriatric; Humans; Infusions, Intravenous; intravenous ketamine; Ketamine - adverse effects; Pilot Projects; Treatment-resistant depression
• ISSN: 1064-7481; 1545-7214
• DOI: 10.1016/j.jagp.2022.11.013

•What is the primary question addressed by this study?This pilot open-label trial assessed the tolerability, safety, and potential clinical benefits of eight weeks of repeated intravenous (IV) ketamine infusions in geriatric treatment-resistant depression.•What is the main finding of this study?IV ketamine was well tolerated with no discontinuation due to adverse effects. Depressive symptoms and cognitive performance improved, with response in depression achieved in 48% of participants.•What is the meaning of the finding?The promising findings of this open pilot study of feasibility, tolerability, and clinical benefit of IV ketamine for TRD in older adults need to be confirmed and extended in a larger randomized controlled trial. Evidence-based treatment options for late-life treatment-resistant depression (TRD) are limited. Ketamine is a promising treatment for TRD; however, there is a paucity of data on its safety and efficacy in older adults. In this pilot clinical trial, 25 adults aged ≥60 years with TRD received IV ketamine openly twice a week for 4 weeks; partial responders at the end of this acute phase were eligible to receive weekly infusions for 4 more weeks in a continuation phase. Acceptability, tolerability, and safety, including adverse and serious adverse events (AEs and SAEs), blood pressure changes, dissociation, craving, in addition to rates of depression response and remission were evaluated. The NIH Toolbox Cognitive Battery was used to assess specific measures of executive function (EF) and overall fluid cognition. Completion rates were 88% for the acute phase and 100% for the continuation phase. No AEs resulted in participant discontinuation, and there were no SAEs. Treatment-emergent elevation of blood pressure, dissociation, and craving were transient and did not result in any participant discontinuation. Depressive symptoms improved significantly and 48% of participants responded. During the acute phase, the EF measures and the fluid cognition composite score improved (Cohen's d = 0.61), and these improvements were sustained in the continuation phase. This pilot study suggests that repeated IV ketamine infusions are well-tolerated and are associated with improvement in depression and EF in older adults with TRD. These promising findings need to be confirmed and extended in a larger randomized controlled trial.