Safety and efficacy of repeated-dose intravenous ketamine for treatment-resistant depression.
Marije Aan Het Rot, Katherine A. Collins, James W. Murrough, Andrew M. Perez, David L. Reich, Dennis S. Charney, Sanjay J. Mathew
Biological Psychiatry January 15, 2010 DOI: 10.1016/j.biopsych.2009.08.038 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Open-label pilot study Peer reviewed |
|---|---|
| Sample size | 10 |
| Population | Medication-free symptomatic patients with treatment-resistant depression who had previously shown a meaningful antidepressant response to a single ketamine dose |
| Intervention | Ketamine |
| Dose | 0.5 mg/kg |
| Duration | Six infusions over 12 days; follow-up twice-weekly for at least 4 weeks or until relapse |
| Measures | Montgomery-Asberg Depression Rating Scale (MADRS) |
| Topics | Depression Esketamine Ketamine |
| Key points | Repeated-dose intravenous ketamine produced large acute antidepressant effects: nine of ten patients met the response criterion after both the first and sixth infusions, with a mean 85% reduction in MADRS scores after the sixth infusion. However, eight of nine responders relapsed on average 19 days after the sixth infusion (range 6-45 days), while one patient remained antidepressant-free for more than three months. The authors suggest these pilot findings support feasibility of repeated-dose IV ketamine for acute treatment of treatment-resistant depression. |
Abstract
A single subanesthetic (intravenous) IV dose of ketamine might have rapid but transient antidepressant effects in patients with treatment-resistant depression (TRD). Here we tested the tolerability, safety, and efficacy of repeated-dose open-label IV ketamine (six infusions over 12 days) in 10 medication-free symptomatic patients with TRD who had previously shown a meaningful antidepressant response to a single dose. On day 1, patients received a 40-min IV infusion of ketamine (.5 mg/kg) in an inpatient setting with continuous vital-sign monitoring. Psychotomimetic effects and adverse events were recorded repeatedly. The primary efficacy measure was change from baseline in the Montgomery-Asberg Depression Rating Scale (MADRS) score. If patients showed a > or =50% reduction in MADRS scores on day 2, they received five additional infusions on an outpatient basis (days 3, 5, 8, 10, and 12). Follow-up visits were conducted twice-weekly for > or =4 weeks or until relapse. Ketamine elicited minimal positive psychotic symptoms. Three patients experienced significant but transient dissociative symptoms. Side effects during and after each ketamine infusion were generally mild. The response criterion was met by nine patients after the first infusion as well as after the sixth infusion. The mean (SD) reduction in MADRS scores after the sixth infusion was 85% (12%). Postketamine, eight of nine patients relapsed, on average, 19 days after the sixth infusion (range 6 days-45 days). One patient remained antidepressant-free with minimal depressive symptoms for >3 months. These pilot findings suggest feasibility of repeated-dose IV ketamine for the acute treatment of TRD.
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 239
- Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial American Journal of Psychiatry August 28, 2013
- Efficacy and Safety of Intranasal Esketamine for the Rapid Reduction of Symptoms of Depression and Suicidality in Patients at Imminent Risk for Suicide: Results of a Double-Blind, Randomized, Placebo-Controlled Study American Journal of Psychiatry April 16, 2018
- Ketamine use: a review Addiction July 21, 2011
- Ketamine and Other NMDA Antagonists: Early Clinical Trials and Possible Mechanisms in Depression American Journal of Psychiatry October 1, 2015
- Better Biomarkers, Faster Drugs, Stronger Models: Progress Towards Precision Psychiatry. Missouri medicine 2023
and 234 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
- Measurement of dissociative states with the Clinician‐Administered Dissociative States Scale (CADSS) Journal of Traumatic Stress 1998
- Riluzole for relapse prevention following intravenous ketamine in treatment-resistant depression: a pilot randomized, placebo-controlled continuation trial The International Journal of Neuropsychopharmacology March 17, 2009
- Treatment of compulsive behaviour in eating disorders with intermittent ketamine infusions The Quarterly journal of medicine July 1, 1998
- Effects of Intravenous Ketamine on Explicit and Implicit Measures of Suicidality in Treatment-Resistant Depression Biological Psychiatry July 9, 2009
and 2 more in the library