Arketamine as adjunctive therapy for treatment-resistant depression: A placebo-controlled pilot study.
Gustavo C. Leal, Breno Souza-Marques, Rodrigo P Mello, Igor D. Bandeira, Ana Teresa Caliman-Fontes, Beatriz A Carneiro, Daniela Faria-Guimarães, Lívia N F Guerreiro-Costa, Ana Paula Jesus-Nunes, Samantha S. Silva, Daniel H Lins-Silva, Mariana A Fontes, Raíza Alves-Pereira, Vivian Cordeiro, Sidelcina Rugieri-Pacheco, Cassio Santos-Lima, Fernanda S. Correia-Melo, Flávia Vieira, Gerard Sanacora, Acioly L T Lacerda, Lucas C Quarantini
Journal of Affective Disorders June 1, 2023 DOI: 10.1016/j.jad.2023.02.151 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized, double-blind, crossover, pilot trial Placebo-controlled Open-label Peer reviewed |
|---|---|
| Sample size | 10 |
| Population | Participants with treatment-resistant depression |
| Intervention | Arketamine |
| Dose | 0.5 mg/kg |
| Duration | One-week interval between treatments; analysis included first week and two weeks together |
| Topics | Depression Ketamine |
| Keywords | Major depression |
| Key findings | Arketamine was not superior to placebo for treatment-resistant depression in this pilot trial. |
Abstract
Racemic ketamine is a mixture of (R)-ketamine (arketamine) and (S)-ketamine (esketamine), with the latter regarded as the main isomer for antidepressant effects. However, preclinical data and one open-label human trial suggest arketamine might exert a more potent and longer-lasting antidepressant effect with fewer side effects. We aimed to explore the feasibility of a randomized controlled trial of arketamine for treatment-resistant depression (TRD) and to assess its efficacy and safety compared to placebo. This is a, randomized, double-blind, crossover, pilot trial (n = 10). All participants received saline and arketamine (0.5 mg/kg) with a one-week interval. Treatment effects were analyzed with a linear mixed effects (LME) model. Our analysis suggested the presence of a carryover effect, so the main efficacy analysis was limited to the first week, which demonstrated a main effect of time (p = 0.038) but not for treatment (p = 0.40) or their interaction (p = 0.95). This indicates that depression improved over time, but without significant difference between arketamine and placebo. Analyzing the two weeks together, findings were the same. Dissociation and other adverse events were minimal. This was a pilot study with a small sample and underpowered. Arketamine was not superior to placebo for TRD but demonstrated to be extremely safe. Our findings reinforce the importance of continuing studies with this drug, with better powered clinical trials, perhaps considering a parallel design with higher or flexible doses and repeated administrations.
Comparable studies
Other randomized controlled trials on ketamine for depression, most cited first.
Citations in the library
Cited by 51
- The Antidepressant Actions of Ketamine and its Enantiomers Pharmacology & Therapeutics May 1, 2023
- Are “mystical experiences” essential for antidepressant actions of ketamine and the classic psychedelics? European Archives of Psychiatry and Clinical Neuroscience February 27, 2024
- Ketamine, Esketamine, and Arketamine: Their Mechanisms of Action and Applications in the Treatment of Depression and Alleviation of Depressive Symptoms. Biomedicines October 9, 2024
- Redefining Ketamine Pharmacology for Antidepressant Action: Synergistic NMDA and Opioid Receptor Interactions? American Journal of Psychiatry March 1, 2025
- Ketamine and Esketamine in Clinical Trials: FDA-Approved and Emerging Indications, Trial Trends With Putative Mechanistic Explanations. Clinical Pharmacology & Therapeutics February 1, 2025
and 46 more in the library
Cites 25
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- Efficacy and Safety of Intranasal Esketamine Adjunctive to Oral Antidepressant Therapy in Treatment-Resistant Depression JAMA Psychiatry December 27, 2017
- 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
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