Pharmacopsychiatry 2024; 57(01): 35-40
DOI: 10.1055/a-2179-8884
Original Paper

Factors Associated with Antidepressant Effects of Ketamine: A Reanalysis of Double-Blind Randomized Placebo-Controlled Trial of Intravenous Ketamine for Treatment-Resistant Depression

Kengo Yonezawa
1   Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan
Hiroyuki Uchida
1   Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan
Taisuke Yatomi
1   Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan
Yohei Ohtani
1   Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan
Kie Nomoto-Takahashi
1   Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan
Shinichiro Nakajima
1   Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan
Masaru Mimura
1   Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan
Hideaki Tani
1   Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan
› Author Affiliations
Funding Information SENSHIN Medical Research Foundation —; Japan Society for the Promotion of Science KAKENHI — 22H03001 Japan Research Foundation for Clinical Pharmacology —; Keio Next-Generation Research Project Program —

Clinical Trials Registration: Trial Registration Data used in this secondary analysis were obtained from, identifier: NCT01920555


Introduction Predictors of treatment response to intravenous ketamine remain unclear in patients with treatment-resistant depression (TRD); therefore, this study aimed to clarify these predictors using the US National Institutes of Health database of clinical trials.

Methods Data from a placebo-controlled, double-blind, randomized controlled trial were used to assess the efficacy of intravenous ketamine in adult patients with TRD (NCT01920555). For the analysis, data were used from the participants who had received therapeutic doses of intravenous ketamine (i. e., 0.5 and 1.0 mg/kg). Logistic and multivariable regression analyses were conducted to explore the demographic and clinical factors associated with response to treatment or changes in the Hamilton Depression Rating Scale 6 items (HAM-D-6) total score.

Results This study included 31 patients with TRD (13 women; mean±standard deviation age, 48.4±10.9 years). Logistic regression analysis showed that the age of onset was positively correlated with treatment response after three days of ketamine administration (β=0.08, p=0.037); however, no association was observed between treatment response and age, sex, baseline HAM-D-6 total score, or dissociative score assessed with the Clinician-Administered Dissociative States Scale 40 min after ketamine infusion. Multiple regression analysis showed that no factors were correlated significantly with the percentage change in the HAM-D-6 total score three days after ketamine administration.

Discussion Later disease onset correlates with a better treatment response three days after ketamine infusion in patients with TRD. Glutamatergic signal transmission may be impaired in patients with an earlier onset of depression, resulting in decreased neuroplasticity, which diminishes ketamine response.

Publication History

Received: 30 July 2023
Received: 01 September 2023

Accepted: 13 September 2023

Article published online:
16 October 2023

© 2023. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

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