Ketamine is a non-competitive antagonist at the N-methyl-D-aspartate (NMDA) glutamate receptor. It was approved by the US Food and Drug Administration for anesthesia in 1970. The only other related US regulatory approval since then has been for esketamine nasal spray for depression in 2019. Over this time ketamine has been repurposed by mainly academic researchers, reporting clinical activity...
Aims: To review and compare the safety, efficacy, cost-effectiveness and remission rates of electroconvulsive therapy (ECT) versus ketamine in patients with major depressive episodes. Methods: A narrative review of the literature was undertaken, focusing on randomised and non-randomised clinical trials, systematic reviews, and meta-analyses comparing ketamine and ECT in adults with major...
Ketamine exerts rapid antidepressant effects. However, currently available ketamine-based treatments are associated with dissociative and cardiovascular adverse effects. To evaluate the antidepressant efficacy and tolerability of KET01, a novel, oral, prolonged-release racemic ketamine tablet formulation. KET01-03 was an active-comparator, double-blind, double-dummy, crossover phase 1...
Treatment-resistant depression is a condition with significant morbidity, despite the current standard of treatment, including traditional pharmacotherapy, psychotherapy, augmentation strategies and electroconvulsive therapy. While novel therapies have emerged, such as ketamine/esketamine, transcranial magnetic stimulation and psilocybin-assisted therapy, the uptake of these treatments is...
Major Depressive Disorder (MDD) affects millions globally, with approximately 30% of patients experiencing treatment-resistant depression (TRD). While ketamine has emerged as a rapid-acting intervention, response rates remain variable, underscoring the need to refine precision medicine approaches for ketamine treatment. Network theories of mental health disorders have been promoted as framework...
Ketamine, including its enantiomers (S)-ketamine (esketamine) and (R)-ketamine (arketamine), has demonstrated rapid antidepressant effects in major depressive disorder (MDD) and bipolar disorder (BD), yet clinical responses vary widely, highlighting the need to identify mechanisms underlying treatment efficacy and related potential predictors. Growing evidence suggests that alterations in sleep...
The past two decades have seen a remarkable renaissance in research on psychedelic drugs and ketamine. Following decades of regulatory restriction that severely limited, especially clinical research, a growing body of evidence has shown that psychedelics such as lysergic acid diethylamide and psilocybin can have long-lasting beneficial effects for treatment-resistant depression, drug and...
BACKGROUND: Over the past decade, neuropsychopharmacology has shifted from stagnation to momentum, with first-in-class mechanisms and biomarker-enabled trials spanning psychiatry and neurology. METHODS: We narratively synthesized advances from 2013 to 2026 across central nervous system (CNS) discovery and development, including pivotal trials, regulatory actions, digital/real-world evidence,...
Brain Research BulletinMay 1, 2026Ladina Philomena Gubser, Anna Stefania Trippel, Niklaus Zoelch et al.
Ketamine has been shown to modulate glutamate signaling in animals and may therefore have the potential to restore glutamate imbalances in the brain. Impaired glutamate homeostasis has been implicated in mental health disorders such as substance use disorders (SUDs). Thus, we investigated ketamine's potential to increase glutamate levels in the nucleus accumbens (NAc), a key region for the...
To synthesize evidence on pharmacological treatments for major depressive disorder (MDD) to inform updated Brazilian clinical guidelines. This overview included systematic reviews and meta-analyses published in the last 10 years, identified through MEDLINE, Cochrane Library, and SciELO. Eligible studies involved adults with MDD receiving pharmacological interventions. Risk of bias was assessed...