Intravenous arketamine for treatment-resistant depression: open-label pilot study
Gustavo C. Leal, Igor D. Bandeira, Fernanda S. Correia-Melo, Manuela Telles, Rodrigo P Mello, Flávia Vieira, Cássio S. Lima, A. P. Jesus-Nunes, Lívia N F Guerreiro-Costa, Roberta F. Marback, A. T. Caliman-Fontes, Breno L. S. Marques, M. L. O. Bezerra, A. Dias-Neto, Samantha S. Silva, A. Sampaio, Gerard Sanacora, Gustavo Turecki, Colleen Loo, Acioly L T Lacerda, Lucas C Quarantini
European Archives of Psychiatry and Clinical Neuroscience February 20, 2020 DOI: 10.1007/s00406-020-01110-5 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Open-label pilot trial Pilot study Peer reviewed |
|---|---|
| Sample size | 7 |
| Population | Humans with treatment-resistant depression |
| Intervention | Arketamine |
| Dose | 0.5 mg/kg |
| Duration | 24 hours |
| Topics | Depression Ketamine |
| Citations | 257 |
| Key findings | A single intravenous infusion of arketamine produced a rapid and substantial reduction in depression severity, with minimal dissociative side effects, in seven people with treatment-resistant depression. |
Abstract
We aimed to analyze the efficacy and safety of arketamine, the R (−)-enantiomer of ketamine, for treatment-resistant depression (TRD) in humans. Open-label pilot trial, seven subjects with TRD received a single intravenous infusion of arketamine (0.5 mg/kg); primary outcome was change in Montgomery–Åsberg Depression Rating Scale (MADRS) 24 h after. Mean MADRS dropped from 30.7 before infusion to 10.4 after one day, a mean difference of 20.3 points [CI 95% 13.6–27.0; p < 0.001]; dissociation was nearly absent. Arketamine might produce fast-onset and sustained antidepressant effects in humans with favorable safety profile, like previously reported with animals; further controlled-trials are needed.
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 |
| 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 |
| Neural correlates of change in major depressive disorder anhedonia following open-label ketamine Medication-free treatment-refractory patients with major depressive disorder | 2015 | Open-label investigation with exploratory re-analysis |
Citations in the library
Cited by 123
- Pharmacological and behavioral divergence of ketamine enantiomers: implications for abuse liability Molecular Psychiatry April 15, 2021
- Hallucinogens in Mental Health: Preclinical and Clinical Studies on LSD, Psilocybin, MDMA, and Ketamine Journal of Neuroscience November 30, 2020
- Ketamine: A tale of two enantiomers Journal of Psychopharmacology November 6, 2020
- Molecular mechanisms underlying the antidepressant actions of arketamine: beyond the NMDA receptor Molecular Psychiatry May 7, 2021
- Molecular mechanisms of the rapid-acting and long-lasting antidepressant actions of (R)-ketamine. Biochemical Pharmacology July 1, 2020
and 118 more in the library
Cites 16
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- Ketamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms Pharmacological Reviews June 26, 2018
- 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 Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study American Journal of Psychiatry May 21, 2019
- Measurement of dissociative states with the Clinician‐Administered Dissociative States Scale (CADSS) Journal of Traumatic Stress 1998
and 11 more in the library