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

Hanadi Ajam Oughli, Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, CA.
Marie Anne Gebara, Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA. Electronic address: gebarama@upmc.edu.
Adam Ciarleglio, Department of Biostatistics and Bioinformatics, Milken Institute School of Public Health, the George Washington University, Washington, DC.
Helen Lavretsky, Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, CA.
Patrick J. Brown, Department of Psychiatry, Columbia University College of Physicians and Surgeons and the New York State Psychiatric Institute, New York, NY.
Alastair J. Flint, Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, Canada; Centre for Mental Health, University Health Network, Toronto, Canada.
Nuri B. Farber, Department of Psychiatry, Washington University School of Medicine, St. Louis, MO.
Jordan F. Karp, Department of Psychiatry, College of Medicine-Tucson, University of Arizona, Tucson, AZ.
Benoit H. Mulsant, Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, Canada; Centre for Addiction and Mental Health, Toronto, Canada.
Charles F. Reynolds, Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA.
Steven P. Roose, Department of Psychiatry, Columbia University College of Physicians and Surgeons and the New York State Psychiatric Institute, New York, NY.
Lei Yang, Department of Psychiatry, Washington University School of Medicine, St. Louis, MO.
Meryl A. Butters, Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA.
Eric J. Lenze, Department of Psychiatry, Washington University School of Medicine, St. Louis, MO.

Document Type

Journal Article

Publication Date

12-5-2022

Journal

The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry

DOI

10.1016/j.jagp.2022.11.013

Keywords

Treatment-resistant depression; cognition; geriatric; intravenous ketamine

Abstract

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Department

Biostatistics and Bioinformatics

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