Pilot Randomized Controlled Trial of Titrated Subcutaneous Ketamine in Older Patients with Treatment-Resistant Depression

George, Duncan; Gálvez, Verònica; Martin, Donel; Kumar, Divya; Leyden, John; Hadzi-Pavlovic, Dusan; Harper, Simon; Brodaty, Henry; Glue, Paul; Taylor, Rohan; Mitchell, Philip B.; Loo, Colleen K.

doi:10.1016/j.jagp.2017.06.007

Cited by 149Treatment of Major DepressionElectroconvulsive Therapy StudiesTranscranial Magnetic Stimulation Studies

Pilot Randomized Controlled Trial of Titrated Subcutaneous Ketamine in Older Patients with Treatment-Resistant Depression

George, Duncan, Gálvez, Verònica, Martin, Donel, Kumar, Divya, Leyden, John, Hadzi-Pavlovic, Dusan, Harper, Simon, Brodaty, Henry +4 more·2017·The American Journal of Geriatric Psychiatry

DOI 10.1016/j.jagp.2017.06.007

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Abstract

Objective To assess the efficacy and safety of subcutaneous ketamine for geriatric treatment-resistant depression. Secondary aims were to examine if repeated treatments were safe and more effective in inducing or prolonging remission than a single treatment. Methods In this double-blind, controlled, multiple-crossover study with a 6-month follow-up (randomized controlled trial [RCT] phase), 16 participants (≥60 years) with treatment-resistant depression who relapsed after remission or did not remit in the RCT were administered an open-label phase. Up to five subcutaneous doses of ketamine (0.1, 0.2, 0.3, 0.4, and 0.5 mg/kg) were administered in separate sessions (≥1 week apart), with one active control (midazolam) randomly inserted (RCT phase). Twelve ketamine treatments were given in the open-label phase. Mood, hemodynamic, and psychotomimetic outcomes were assessed by blinded raters. Remitters in each phase were followed for 6 months. Results Seven of 14 RCT-phase completers remitted with ketamine treatment. Five remitted at doses below 0.5 mg/kg. Doses ≥ 0.2 mg/kg were significantly more effective than midazolam. Ketamine was well tolerated. Repeated treatments resulted in higher likelihood of remission or longer time to relapse. Conclusion Results provide preliminary evidence for the efficacy and safety of ketamine in treating elderly depressed. Dose titration is recommended for optimizing antidepressant and safety outcomes on an individual basis. Subcutaneous injection i…

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George et al. (2017) showed improvement in depressive symptoms with subcutaneous ketamine in treatment-resistant depression.
“Improvement in depressive symptoms”
From Virtual reality and psychedelics for the treatment of psychiatric disease: A systematic literature review (2020) · cites this paper as George et al. (2017)
In older patients (≥60 years) with treatment-resistant depression, subcutaneous ketamine produced acute response and remission rates of 68.8% (11 of 16 participants).
“The results reported acute response and remission rates of 68.8% in 11 of 16 participants”
From Virtual reality and psychedelics for the treatment of psychiatric disease: A systematic literature review (2020) · cites this paper as George et al. (2017)
Subcutaneous ketamine caused discrete increases in heart rate and blood pressure and occasional reports of mild neurological symptoms.
“causing discrete increases in heart rate and blood pressure, and occasional reports of mild neurological symptoms.”
From Virtual reality and psychedelics for the treatment of psychiatric disease: A systematic literature review (2020) · cites this paper as George et al. (2017)
Subcutaneously administered ketamine in older patients was effective, safe, and well tolerated.
“concluding that in general, subcutaneously administered ketamine in older patients was effective, safe and well tolerated”
From Virtual reality and psychedelics for the treatment of psychiatric disease: A systematic literature review (2020) · cites this paper as George et al. (2017)

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A systematic review of ketamine for the treatment of depression among older adults
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Authors: George, D., Gálvez, V., Martin, D., Kumar, D., Leyden, J., Hadzi-Pavlovic, D., Harper, S., Brodaty, H., Glue, P., Taylor, R., Mitchell, P. B., & Loo, C. K.
Affiliations: Black Dog Institute (AU)
UNSW Sydney (AU)
Royal North Shore Hospital (AU)
Wesley Hospital (AU)
University of Otago (NZ)
Corresponding author: Loo, Colleen K.
ORCID: George, Duncan
Gálvez, Verònica
Martin, Donel
Leyden, John
Brodaty, Henry
Glue, Paul
Mitchell, Philip B.
Loo, Colleen K.
Venue: The American Journal of Geriatric Psychiatry
Publisher: Elsevier BV
Published: 2017-11
Volume: 25
Issue: 11
Pages: 1199-1209
ISSN: 1064-7481 (ISSN-L)
DOI: 10.1016/j.jagp.2017.06.007
OpenAlex: W2625860417
Cited by: 149
References: 29
Citations by year: 2026: 10 · 2025: 17 · 2024: 37 · 2023: 13 · 2022: 17 · 2021: 21 · 2020: 16 · 2019: 4 · 2018: 10 · 2017: 4
FWCI: 6.51
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: American Journal of Geriatric Psychiatry (publishedVersion)
PubMed (publishedVersion)
Funders: NSW Institute of Psychiatry
University of Barcelona
NARSAD
Topics: Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
Health Sciences › Medicine › Psychiatry and Mental health › Electroconvulsive Therapy Studies
Life Sciences › Neuroscience › Neurology › Transcranial Magnetic Stimulation Studies
Keywords: subcutaneous ketamine, treatment-resistant depression, geriatric depression, older adults, dose titration, remission, relapse, psychotomimetic effects, antidepressant efficacy, drug safety
MeSH terms: Aged, Double-Blind Method, Drug Administration Schedule, Female, Follow-Up Studies, Humans, Hypnotics and Sedatives, Injections, Subcutaneous, Ketamine, Male, Midazolam, Middle Aged, Pilot Projects, Remission Induction, Outcome Assessment, Health Care, Cross-Over Studies, Excitatory Amino Acid Antagonists, Depressive Disorder, Treatment-Resistant

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Pilot Randomized Controlled Trial of Titrated Subcutaneous Ketamine in Older Patients with Treatment-Resistant Depression

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