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 via PubMed
Summary
AI-generated from the abstractIn a small pilot trial, the antidepressant arketamine was compared with placebo for treatment-resistant depression. Ten participants received both arketamine (0.5 mg/kg) and saline one week apart in a randomized, double-blind, crossover design. Depression improved over time, but there was no significant difference between arketamine and placebo. Dissociation and other adverse events were minimal. The study was underpowered, and the authors conclude that arketamine was not superior to placebo but was extremely safe, recommending larger trials with different dosing strategies.
Study at a glance
| 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 finding | 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.