Continuation phase intravenous ketamine in adults with treatment-resistant depression.
Jennifer L. Vande Voort, Robert J Morgan, Simon Kung, Keith G Rasmussen, Jose A Rico, Brian A. Palmer, Kathryn M Schak, Susannah J. Tye, Matthew J. Ritter, Mark A Frye, William V Bobo
Journal of Affective Disorders December 2016 DOI: 10.1016/j.jad.2016.09.008 (opens in new tab)
The journal has published a correction to this paper. Read the correction (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Uncontrolled feasibility study Peer reviewed |
|---|---|
| Sample size | 12 |
| Population | Adults with treatment-resistant non-psychotic unipolar or bipolar major depression and suicidal ideation |
| Intervention | Ketamine |
| Dose | 0.5 mg/kg administered over 100 minutes |
| Duration | Up to 6 thrice-weekly acute-phase infusions, then 4 weekly continuation infusions, followed by 4 weeks of post-continuation follow-up |
| Topics | Depression Ketamine Esketamine |
| Keywords | Bipolar depression Continuation Major depression Repeated Treatment resistant |
| Registration | NCT02094898 |
| Key points | Among 12 participants, 5 (41.7%) remitted and 7 (58.3%) responded during acute-phase intravenous ketamine treatment. All five acute-phase remitters showed further improvement during weekly continuation infusions, and the antidepressant effect persisted for several weeks after continuation ended, though four of the five lost remission status during post-continuation follow-up while remaining responders. The authors argue weekly continuation ketamine can extend remission and that high-suicide-risk non-responders need close monitoring. |
Abstract
Little is known about the antidepressive effects of repeated intravenous ketamine infusions beyond the acute phase of treatment in patients with refractory depression. Twelve subjects with treatment-resistant non-psychotic unipolar or bipolar major depression and suicidal ideation were given repeated (up to 6) thrice-weekly acute-phase intravenous infusions of ketamine (0.5mg/kg, administered over 100min). Those who remitted during acute-phase treatment received continuation-phase treatment that consisted of 4 weekly ketamine infusions, followed by 4 weeks of post-continuation phase follow-up (during which no further ketamine infusions were administered). Clinical measures were assessed at baseline, at 24h following each infusion, at the last acute-phase observation, and during continuation and post-continuation follow-up (acute phase remitters only). Of the 12 enrollees, 5 (41.7%) remitted and 7 (58.3%) responded to ketamine treatment during the acute-phase. All five subjects who remitted during the acute-phase experienced further depressive symptom improvement during continuation-phase treatment. Four subjects lost remission status during the post-continuation phase, but all were still classified as positive treatment responders at the end of the post-continuation phase. Adverse effects were generally mild and transient during acute- and continuation-phase treatment; however, one subject developed behavioral outbursts and suicide threats during follow-up while hospitalized, and one subject died by suicide several weeks after the end of follow-up. This was an uncontrolled feasibility study with a small sample size. The continuation-phase administration of ketamine at weekly intervals to patients with treatment-resistant depression who remitted during acute-phase ketamine treatment can extend the duration of depressive symptom remission. The antidepressive effect of ketamine persisted for several weeks after the end of continuation-phase treatment. Our results highlight the need for close monitoring of subjects who are at high baseline risk for suicide but do not respond clinically to ketamine. CLINICALTRIALS. NCT02094898.
Comparable studies
Other non-randomized and open-label trials on ketamine for depression, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Rapid Resolution of Suicidal Ideation After a Single Infusion of anN-Methyl-D-Aspartate Antagonist in Patients With Treatment-Resistant Major Depressive Disorder Subjects with DSM-IV-diagnosed treatment-resistant major depressive disorder | 2010 | Open-label trial | n = 33 |
| Esketamine Nasal Spray Plus Oral Antidepressant in Patients With Treatment-Resistant Depression Adults (≥ 18 years) with treatment-resistant depression | 2020 | Phase 3, open-label, multicenter, long-term study | n = 802 |
| Intravenous arketamine for treatment-resistant depression: open-label pilot study Humans with treatment-resistant depression | 2020 | Open-label pilot trial | n = 7 |
| A Phase 2 Open Label Study of Efficacy, Safety, and Tolerability of SLS-002 (Intranasal Racemic Ketamine) in Adults with MDD at Imminent Risk of Suicide. Hospitalized patients with Major Depressive Disorder and acute suicidal ideation and... | 2024 | Open label study | n = 17 |
| Ketamine Safety and Tolerability in Clinical Trials for Treatment-Resistant Depression Participants with DSM-IV-defined major depressive disorder and treatment-resistant... | 2014 | Pooled analysis of three clinical trials | n = 97 |
Citations in the library
Cited by 49
- The effect of a single dose of intravenous ketamine on suicidal ideation: a systematic review and individual participant data meta-analysis American Journal of Psychiatry October 3, 2017
- A Consensus Statement on the Use of Ketamine in the Treatment of Mood Disorders JAMA Psychiatry March 1, 2017
- Single, Repeated, and Maintenance Ketamine Infusions for Treatment-Resistant Depression: A Randomized Controlled Trial. American Journal of Psychiatry March 29, 2019
- A Phase 2 Open Label Study of Efficacy, Safety, and Tolerability of SLS-002 (Intranasal Racemic Ketamine) in Adults with MDD at Imminent Risk of Suicide. Psychopharmacology Bulletin March 4, 2024
- Real-world effectiveness of ketamine in treatment-resistant depression: A systematic review & meta-analysis. Journal of Psychiatric Research May 1, 2022
and 44 more in the library
Cites 7
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- A Randomized Add-on Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Bipolar Depression Archives of General Psychiatry August 1, 2010
- Ketamine and Other NMDA Antagonists: Early Clinical Trials and Possible Mechanisms in Depression American Journal of Psychiatry October 1, 2015
- A Double-Blind, Randomized, Placebo-Controlled, Dose-Frequency Study of Intravenous Ketamine in Patients With Treatment-Resistant Depression American Journal of Psychiatry April 8, 2016
- The use of ketamine as an antidepressant: a systematic review and meta‐analysis Human Psychopharmacology: Clinical and Experimental April 7, 2015
and 2 more in the library