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Randomized Controlled Trial
. 2018 Dec 1:241:103-109.
doi: 10.1016/j.jad.2018.07.073. Epub 2018 Jul 29.

Ketamine augmentation for major depressive disorder and suicidal ideation: Preliminary experience in an inpatient psychiatry setting

Mark Sinyor  1 , Marissa Williams  2 , Sue Belo  3 , Beverley Orser  4 , Margaret Vincent  5 , Linda Mah  6 , Carlos Zarate Jr  7 , Saulo Castel  8 , Anthony J Levitt  8 , Ayal Schaffer  8
Affiliations
Randomized Controlled Trial

Ketamine augmentation for major depressive disorder and suicidal ideation: Preliminary experience in an inpatient psychiatry setting

Mark Sinyor et al. J Affect Disord. .

Abstract

Background: Ketamine is known to rapidly reduce depressive symptoms and suicidal ideation (SI) in patients with major depressive disorder (MDD), but evidence is limited for its acceptability and effectiveness in "real-world" settings. This case series examines serial ketamine infusions in reducing SI and depression scores in adults with MDD admitted to a tertiary care hospital.

Methods: Five inpatients with MDD and SI admitted to hospital in Toronto, Canada received six infusions of 0.5 mg/kg intravenous (IV) ketamine (n = 5) over approximately 12 days, in addition to treatment-as-usual. Suicide and depression rating scores (Scale for Suicidal Ideation, SSI; Montgomery-Åsberg Depression Rating Scale, MADRS) were obtained at baseline, on treatment days, on days 14 and 42 (primary endpoint).

Results: All patients experienced benefit with ketamine. SSI scores diminished by 84% from 14.0 ± 4.5 at baseline to 2.2 ± 2.5 at study endpoint. MADRS scores diminished by 47% from 42.2 ± 5.3 at baseline to 22.4 ± 8.0. Two patients withdrew from the study, one to initiate electroconvulsive therapy and one due to an adverse event (dissociative effects) during the ketamine infusion.

Limitations: The major limitation of this study is the small sample size.

Discussion: These preliminary pilot data are promising with a greater than two-fold reduction in SI following ketamine infusions. They demonstrate that six serial ketamine infusions may be safe and feasible. These findings support the need for large scale randomized controlled trials to confirm the efficacy of serial ketamine for treatment of SI in "real-world" settings.

Keywords: Inpatients; Ketamine; Major depressive disorder; Midazolam; Suicide.

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Conflict of interest statement

Conflict of interest disclosures

Dr. Zarate is listed as a coinventor on a patent for the use of ketamine in major depression and suicidal ideation. Dr. Zarate is listed as a co-inventor on a patent for the use of (2R,6R)-hydroxynorketamine, (S)-dehydronorketamine and other stereoisomeric dehydro and hydroxylated metabolites of (R,S)-ketamine metabolites in the treatment of depression and neuropathic pain. Dr. Zarate is listed as co-inventor on a patent application for the use of (2R,6R)-hydroxynorketamine and (2S,6S)-hydroxynorketamine in the treatment of depression, anxiety, anhedonia, suicidal ideation and post-traumatic stress disorders. Dr. Zarate has assigned his patent rights to the U.S. government but will share a percentage of any royalties that may be received by the government. The other authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Fig. 1.
Fig. 1.
Flow diagram indicating the number of patients screened, randomized, intervention allocation, follow-up, and data analysis.
Fig. 2.
Fig. 2.
Scale of suicidal ideation (A) and Montgomery–Åsberg depression rating scale (B) Scores at baseline, after the first infusion, at day 14 and 42 in subjects receiving ketamine (K1-5).
Fig. 3.
Fig. 3.
Scale of suicidal ideation (A) and Montgomery–Åsberg depression rating scale (B) Scores at baseline, after the first infusion, at day 14 and 42 in subjects receiving midazolam (M1-4).
See this image and copyright information in PMC

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