Arketamine for bipolar depression: Open-label, dose-escalation, pilot study

Bandeira, Igor D.; Leal, Gustavo; Correia-Melo, Fernanda S.; Souza-Marques, Breno; Silva, Samantha S.; Lins-Silva, Daniel H.; Mello, Rodrigo P.; Vieira, Flávia; Dorea-Bandeira, Ingrid; Faria-Guimarães, Daniela; Carneiro, Beatriz; Caliman-Fontes, Ana Teresa; Kapczinski, Flávio; Miranda‐Scippa, Ângela; Lacerda, Acioly L.T.

doi:10.1016/j.jpsychires.2023.06.028

Cited by 7 publications

(6 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thus, novel rapid‐response antidepressant drugs are needed for these patients. The previous pilot studies indicated that R ‐(−)‐ketamine produces rapid and significant effects in the treatment of TRD and bipolar depression 57,58 . The response rates of patients with bipolar depression and TRD to ketamine at 4 h were >50% 59,60 .…”

Section: Antidepressant Effects Of Ketaminementioning

confidence: 99%

“…The previous pilot studies indicated that R-(−)-ketamine produces rapid and significant effects in the treatment of TRD and bipolar depression. 57,58 The response rates of patients with bipolar depression and TRD to ketamine at 4 h were >50%. 59,60 Ketamine can affect the functional connectivity between the cortex and striatum in depressed individuals and thereby produce antidepressant effects, 61 although some contradictory results have been reported.…”

Section: Antidepre Ssant Effec Ts Of Ke Taminementioning

confidence: 99%

See 1 more Smart Citation

The role of NMDARs in the anesthetic and antidepressant effects of ketamine

Zhou,

Duan

2023

CNS Neurosci Ther

View full text Add to dashboard Cite

BackgroundAs a phencyclidine (PCP) analog, ketamine can generate rapid‐onset and substantial anesthetic effects. Contrary to traditional anesthetics, ketamine is a dissociative anesthetic and can induce loss of consciousness in patients. Recently, the subanaesthetic dose of ketamine was found to produce rapid‐onset and lasting antidepressant effects.AimHowever, how different concentrations of ketamine can induce diverse actions remains unclear. Furthermore, the molecular mechanisms underlying the NMDAR‐mediated anesthetic and antidepressant effects of ketamine are not fully understood.MethodIn this review, we have introduced ketamine and its metabolism, summarized recent advances in the molecular mechanisms underlying NMDAR inhibition in the anesthetic and antidepressant effects of ketamine, explored the possible functions of NMDAR subunits in the effects of ketamine, and discussed the future directions of ketamine‐based anesthetic and antidepressant drugs.ResultBoth the anesthetic and antidepressant effects of ketamine were thought to be mediated by N‐methyl‐D‐aspartate receptor (NMDAR) inhibition.ConclusionThe roles of NMDARs have been extensively studied in the anaesthetic effects of ketamine. However, the roles of NMDARs in antidepressant effects of ketamine are complicated and controversial.

show abstract

Section: Antidepressant Effects Of Ketaminementioning

confidence: 99%

Section: Antidepre Ssant Effec Ts Of Ke Taminementioning

confidence: 99%

The role of NMDARs in the anesthetic and antidepressant effects of ketamine

Zhou,

Duan

2023

CNS Neurosci Ther

View full text Add to dashboard Cite

show abstract

“…Thus, although this small pilot study by LEAL et al (Leal et al, 2023) failed to demonstrate that a single intravenous infusion of (R)-ketamine was superior to placebo in improving depression, the possibility that (R)ketamine has antidepressant effects in humans cannot be completely discounted (R)-ketamine may provide positive clinical benefits, at least in terms of medication safety and adverse effects. Recent studies on (R)-ketamine in the treatment of bi-directional depression have again demonstrated its favorable antidepressant effects (Bandeira et al, 2023). In the study, six subjects with type I and type II bipolar disorders were treated with (R)-ketamine intravenously on two separate occasions (1 week apart) at doses of 0.5 mg/kg and 1 mg/kg, respectively).…”

Section: Clinical Researchmentioning

confidence: 99%

Exploring the multifaceted potential of (R)-ketamine beyond antidepressant applications

Zhang,

Pu,

Liu

et al. 2024

Front. Pharmacol.

View full text Add to dashboard Cite

(R, S)- and (S)-ketamine have made significant progress in the treatment of treatment-resistant depression (TRD) and have become a research focus in recent years. However, they both have risks of psychomimetic effects, dissociative effects, and abuse liability, which limit their clinical use. Recent preclinical and clinical studies have shown that (R)-ketamine has a more efficient and lasting antidepressant effect with fewer side effects compared to (R, S)- and (S)-ketamine. However, a recent small-sample randomized controlled trial found that although (R)-ketamine has a lower incidence of adverse reactions in adult TRD treatment, its antidepressant efficacy is not superior to the placebo group, indicating its antidepressant advantage still needs further verification and clarification. Moreover, an increasing body of research suggests that (R)-ketamine might also have significant applications in the prevention and treatment of medical fields or diseases such as cognitive disorders, perioperative anesthesia, ischemic stroke, Parkinson’s disease, multiple sclerosis, osteoporosis, substance use disorders, inflammatory diseases, COVID-19, and organophosphate poisoning. This article briefly reviews the mechanism of action and research on antidepressants related to (R)-ketamine, fully revealing its application potential and development prospects, and providing some references and assistance for subsequent expanded research.

show abstract

“…Both isomers exhibited antidepressant effects, but experimental data suggest that (R)‐ketamine exhibited more powerful antidepressant effects 12 and lower side effects than (S)‐ketamine and (R,S)‐ketamine 13,14 . Also, R‐ketamine has been reported to be effective in bipolar disorder 15 . Following clinical trial evaluation, on March 5, 2019, the U.S. Food and Drug Administration (FDA) approved Janssen Pharmaceuticals' Spravato (esketamine, S‐ketamine) nasal spray in combination with an oral antidepressant for use in refractory depression with risk of suicide.…”

Section: Introductionmentioning

confidence: 99%

“…13,14 Also, R-ketamine has been reported to be effective in bipolar disorder. 15 Following clinical trial evaluation, on March 5, 2019, the U.S. Food and Drug Administration (FDA) approved Janssen Pharmaceuticals' Spravato (esketamine, S-ketamine) nasal spray in combination with an oral antidepressant for use in refractory depression with risk of suicide. Notably, this was the landmark endorsement by the FDA for the use of any compounds in the ketamine series for therapeutic purposes.…”

mentioning

confidence: 99%

A novel NMDA receptor modulator: the antidepressant effect and mechanism of GW043

Tiliwaerde,

Gao,

Yang

et al. 2024

CNS Neurosci Ther

View full text Add to dashboard Cite

AimsThe N‐methyl‐D‐aspartate (NMDA) receptor (NMDAR) has been proven to be strongly correlated with rapid antidepressant effects. Here, GW043, as a new compound targeting NMDAR, we explored its antidepressant effects and its mechanism of action.MethodsOur study utilized electrophysiological techniques to confirm the effect of GW043 on NMDAR currents. Additionally, we assessed the selectivity of GW043 through high‐throughput receptor‐ligand binding experiments. The antidepressant properties of GW043 were examined using rodent behavioral models including the Forced Swim Test (FST), Tail Suspension Test (TST), and Chronic Unpredictable Mild Stress (CUMS). Mechanistic insight into GW043's onset was gained through western blot analysis, BrdU staining, Golgi staining, and electrophysiological techniques.ResultsElectrophysiological studies indicated that GW043 acts as a partial agonist of NMDAR. Behavioral experiments confirmed the antidepressant effect of GW043 in rodents. Mechanistic investigations revealed that GW043 modulates synaptic plasticity through the LTP and BDNF‐mTOR pathways, consequently leading to an increase in the number of newborn neurons and subsequent antidepressant effects.ConclusionOur findings disclose that GW043, as a partial agonist of NMDAR, can reverse depression‐like behaviors in rats by modulating synaptic plasticity, indicating its potential as an antidepressant agent.

show abstract

Arketamine for bipolar depression: Open-label, dose-escalation, pilot study

Cited by 7 publications

References 25 publications

The role of NMDARs in the anesthetic and antidepressant effects of ketamine

The role of NMDARs in the anesthetic and antidepressant effects of ketamine

Exploring the multifaceted potential of (R)-ketamine beyond antidepressant applications

A novel NMDA receptor modulator: the antidepressant effect and mechanism of GW043

Contact Info

Product

Resources

About