Cited by 433Treatment of Major DepressionElectroconvulsive Therapy StudiesTryptophan and brain disorders

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Double-blind, placebo-controlled, dose-ranging trial of intravenous ketamine as adjunctive therapy in treatment-resistant depression (TRD)

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Fava, Maurizio, Freeman, Marlene P., Flynn, Martina, Judge, Heidi, Hoeppner, Bettina B., Cusin, Cristina, Ionescu, Dawn F., Mathew, Sanjay J., Chang, Lee C., Iosifescu, Dan V., Murrough, James, Debattista, Charles, Schatzberg, Alan F., Trivedi, Madhukar H., Jha, Manish K, Sanacora, Gerard, Wilkinson, Samuel T., Papakostas, George I.·2020·Molecular Psychiatry

DOI 10.1038/s41380-018-0256-5PMC PMC6447473

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Abstract

Numerous placebo-controlled studies have demonstrated the ability of ketamine, an NMDA receptor antagonist, to induce rapid (within hours), transient antidepressant effects when administered intravenously (IV) at subanesthetic doses (0.5 mg/kg over 40 min). However, the optimal antidepressant dose remains unknown. We aimed to compare to active placebo the rapid acting antidepressant properties of a broad range of subanesthetic doses of IV ketamine among outpatients with treatment-resistant depression (TRD). A range of IV ketamine doses were compared to active placebo in the treatment of adult TRD over a 3-day period following a single infusion over 40 min. This was an outpatient study conducted across six US academic sites. Outpatients were 18-70 years old with TRD, defined as failure to achieve a satisfactory response (e.g., less than 50% improvement of depression symptoms) to at least two adequate treatment courses during the current depressive episode. Following a washout period, 99 eligible subjects were randomly assigned to one of the five arms in a 1:1:1:1:1 fashion: a single intravenous dose of ketamine 0.1 mg/kg (n = 18), a single dose of ketamine 0.2 mg/kg (n = 20), a single dose of ketamine 0.5 mg/kg (n = 22), a single dose of ketamine 1.0 mg/kg (n = 20), and a single dose of midazolam 0.045 mg/kg (active placebo) (n = 19). The study assessments (HAM-D-6, MADRS, SDQ, PAS, CGI-S, and CGI-I) were performed at days 0, 1, 3 (endpoint), 5, 7, 14, and 30 to assess the safety and efficacy. The overall group × time interaction effect was significant for the primary outcome measure, the HAM-D-6. In post hoc pairwise comparisons controlling for multiple comparisons, standard dose (0.5 mg/kg) and high dose (1 mg/kg) of intravenous ketamine were superior to active placebo; a low dose (0.1 mg/kg) was significant only prior to adjustment (p = 0.02, p-adj = 0.14, d = -0.82 at day 1). Most of the interaction effect was due to differences at day 1, with no significant adjusted pairwise differences at day 3. This pattern generally held for secondary outcomes. The infusions of ketamine were relatively well tolerated compared to active placebo, except for greater dissociative symptoms and transient blood pressure elevations with the higher doses. Our results suggest that there is evidence for the efficacy of the 0.5 mg/kg and 1.0 mg/kg subanesthetic doses of IV ketamine and no clear or consistent evidence for clinically meaningful efficacy of lower doses of IV ketamine. Trial Registration: NCT01920555.

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A rating scale for depression
Hamilton, M. (1960) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp.23.1.56 · Cited by 32,817
A Simple Sequentially Rejective Multiple Test Procedure
(1979) · Scandinavian Journal of Statistics · doi:10.2307/4615733 · Cited by 21,526
A new depression scale designed to be sensitive to change
Montgomery, S. A., & Åsberg, M. (1979) · British Journal of Psychiatry · doi:10.1192/bjp.134.4.382 · Cited by 13,962
Untitled work
(1976) · Medical Entomology and Zoology · Cited by 8,899
Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: implications for clinical practice
Trivedi, M. H., Rush, A. J., Wisniewski, S. R., Nierenberg, A. A., Warden, D., Ritz, L., Norquist, G., Howland, R. H., Lebowitz, B., McGrath, P. J., et al. (2006) · American Journal of Psychiatry · doi:10.1176/appi.ajp.163.1.28 · Cited by 3,879
Self-citation
Antidepressant effects of ketamine in depressed patients
Berman, R. M., Cappiello, A., Anand, A., Oren, D. A., Heninger, G. R., Charney, D. S., & Krystal, J. H. (2000) · Biological Psychiatry · doi:10.1016/s0006-3223(99)00230-9 · Cited by 3,856
A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression.
Zarate, C. A., Singh, J. B., Carlson, P. J., Brutsche, N. E., Ameli, R., Luckenbaugh, D. A., Charney, D. S., & Manji, H. K. (2006) · Archives of General Psychiatry · doi:10.1001/archpsyc.63.8.856 · Cited by 3,766
The role and interpretation of pilot studies in clinical research
Leon, A. C., Davis, L. L., & Kraemer, H. C. (2011) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2010.10.008 · Cited by 1,917
Efficacy and safety of transcranial magnetic stimulation in the acute treatment of major depression: a multisite randomized controlled trial
O’Reardon, J. P., Solvason, H. B., Janicak, P. G., Sampson, S., Isenberg, K. E., Nahas, Z., McDonald, W. M., Avery, D., Fitzgerald, P. B., Loo, C., et al. (2007) · Biological Psychiatry · doi:10.1016/j.biopsych.2007.01.018 · Cited by 1,910
A scale for the assessment of hedonic tone the Snaith-Hamilton pleasure scale
Snaith, R. P., Hamilton, M., Morley, S., Humayan, A., Hargreaves, D., & Trigwell, P. (1995) · British Journal of Psychiatry · doi:10.1192/bjp.167.1.99 · Cited by 1,778

Show all 35 references

Research works printed but not linked: 1

Fawcett J, Epstein P, Fiester SJ, Elkin I, Autry JH. Clinical management: imipramine/placebo administration manual. Psychopharmacol Bull. 1987;23:309–24.

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“…et al., 2017 [48] 93 Unipolar, bipolar Secondary analysis of trial IV; 0.5 mg/kg Rybakowski et al., 2017 [49] 53 BD Open-label study IV; 0.5 mg/kg Fava et al., 2018 [50] 99 Unipolar Randomized controlled trial IV; 0.1–1.0 mg/kg Niciu et al., 2018 [51] 126 Unipolar, bipolar Secondary analysis of…”
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Treatment resistant depression in a young female successfully treated with a combination of ketamine and pramipexole – A case report
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Plöderl, M., Cooper, R. E., Walker, T., Shah, V., Horowitz, M. A., Volkmann, C., & Moncrieff, J. (2025) · medRxiv · doi:10.1101/2025.08.19.25333796 · Cited by 1
“These included seven of the eight studies that employed an active placebo agent such as midazolam or remifentanil, with some of these finding rates of correct guesses by participants and assessors between 80 and 100% [34,35].”
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“In March 2019 the FDA approved a new nasal spray medication (Esketamine/S-ketamine) for treating depression, but because of safety concerns (such as dizziness, euphoria, sedation, dissociation, misuse potential and addictive potential), it is used only for treatment-resistant depression (TRD) and in conjunction with a…”
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Ketamine prolongs survival in symptomatic SOD1-G93A mice
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“Other groups have reported similar findings (Carlson et al., 2013; Shiroma et al., 2014; Wilkinson et al., 2018; Fava et al., 2020).”
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“These ﬁ ndings differ from studies with esketamine or ketamine for which raters and participants can often correctly guess treatment assignment [16, 17].”
EVIDÊNCIAS EMERGENTES DA EFICÁCIA E SEGURANÇA DA CETAMINA E ESCETAMINA NO TRATAMENTO DA DEPRESSÃO RESISTENTE AO TRATAMENTO
Back, M. S., Santiago, P. R. B., & Pellin, G. M. (2025) · Revista Contemporânea · doi:10.56083/rcv5n2-072
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Patel, A. (2025) · BJPsych Advances · doi:10.1192/bja.2024.84
“However, ketamine studies using i.v. midazolam in the review that tested masking found the masking to be ineffective (Fava 2020; Shiroma 2020).”
Detecting neuroplastic effects induced by ketamine in healthy human subjects: a multimodal approachPreprint
Agnorelli, C., Peill, J. M., Sawicka, G., Kurtin, D. L., Shatalina, E., Ahmad, K., Wall, M. B., Rua, C., Godfrey, K., Erl, N., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.05.01.651686
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A ATUAL EFICÁCIA DA UTILIZAÇÃO DA CETAMINA EM ADULTOS COM DEPRESSÃO RESISTENTE E SEUS EFEITOS: UMA REVISÃO INTEGRATIVA
da Rocha, A. V. A., Neto, E. A. L. D. G., Gomes, M. A., & Netto, J. F. D. S. (2025) · Revista Contemporânea · doi:10.56083/rcv5n5-038
Ketamine
Ramm, R., Wiisanen, M., & DeMarco, M. (2025) · Psychedelics in Palliative Care · doi:10.1093/med/9780197760864.003.0005
Arketamine: Unapproved but Promising Antidepressant with Multiple Brain Benefits
Wan, X., & Hashimoto, K. (2025) · Neuromethods · doi:10.1007/978-1-0716-4599-4_15

Authors: Fava, M., Freeman, M. P., Flynn, M., Judge, H., Hoeppner, B. B., Cusin, C., Ionescu, D. F., Mathew, S. J., Chang, L. C., Iosifescu, D. V., Murrough, J., Debattista, C., Schatzberg, A. F., Trivedi, M. H., Jha, M. K., Sanacora, G., Wilkinson, S. T., & Papakostas, G. I.
Affiliations: Massachusetts General Hospital (US)
Michael E. DeBakey VA Medical Center (US)
Icahn School of Medicine at Mount Sinai (US)
Stanford Medicine (US)
The University of Texas Southwestern Medical Center (US)
Yale University (US)
ORCID: Freeman, Marlene P.
Hoeppner, Bettina B.
Cusin, Cristina
Mathew, Sanjay J.
Chang, Lee C.
Iosifescu, Dan V.
Murrough, James
Debattista, Charles
Schatzberg, Alan F.
Trivedi, Madhukar H.
Jha, Manish K
Sanacora, Gerard
Wilkinson, Samuel T.
Papakostas, George I.
Venue: Molecular Psychiatry
Publisher: Springer Science and Business Media LLC
Published: 2018-10-03
Volume: 25
Issue: 7
Pages: 1592-1603
ISSN: 1359-4184 (ISSN-L)
1476-5578
DOI: 10.1038/s41380-018-0256-5
PMC: PMC6447473
OpenAlex: W2895197076
Cited by: 433
References: 35
Citations by year: 2026: 28 · 2025: 69 · 2024: 79 · 2023: 54 · 2022: 54 · 2021: 59 · 2020: 60 · 2019: 28 · 2018: 1
FWCI: 23.88
Type: journal article
Language: en
Update notices: correction (2019-01-07)
Open access: bronze
doi.org
Licence: www.springernature.com/gp/researchers/text-and-data-mining (tdm)
www.springernature.com/gp/researchers/text-and-data-mining (vor)
Locations: Molecular Psychiatry (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (HHSN271201100006I)
Topics: Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
Health Sciences › Medicine › Psychiatry and Mental health › Electroconvulsive Therapy Studies
Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
Keywords: treatment-resistant depression, intravenous ketamine, rapid-acting antidepressants, dose-response relationship, NMDA receptor antagonists, active placebo, antidepressant efficacy, depression severity, outpatients, antidepressant safety, CGI-S, CGI-I, adjunctive therapy, suicidal ideation
MeSH terms: Adult, Antidepressive Agents, Depression, Double-Blind Method, Female, Humans, Infusions, Intravenous, Ketamine, Male, Middle Aged, Treatment Outcome, Depressive Disorder, Treatment-Resistant

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Double-blind, placebo-controlled, dose-ranging trial of intravenous ketamine as adjunctive therapy in treatment-resistant depression (TRD)

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