Translational Psychiatry
October 14, 2014
Níall Lally, Allison C. Nugent, David A. Luckenbaugh et al.
269 citations
A single infusion of ketamine rapidly reduced anhedonia in 36 patients with treatment-resistant bipolar depression, and this effect occurred independently from reductions in general depressive symptoms. The anti-anhedonic effects were specifically related to increased glucose metabolism in the dorsal anterior cingulate cortex and putamen, highlighting the role of the glutamatergic system in treating such symptoms.
Journal of Psychopharmacology
February 17, 2015
Níall Lally, Allison C. Nugent, David A. Luckenbaugh et al.
224 citations
Anhedonia, a core symptom of major depression that often resists standard treatment, rapidly decreased after a single infusion of the antidepressant ketamine in medication-free patients with treatment-refractory major depressive disorder, and the reduction lasted up to three days. Adding daily oral riluzole or placebo did not alter this effect. In a subgroup, reduced anhedonia correlated with increased glucose metabolism in the hippocampus and dorsal anterior cingulate cortex and decreased metabolism in the inferior frontal gyrus and orbitofrontal cortex. The relationship remained significant in the dorsal anterior cingulate cortex and orbitofrontal cortex, and at trend level in the hippocampus, when controlling for total depression score. Results are tenuous due to the lack of a placebo control for ketamine.
Current Neuropharmacology
March 25, 2016
Brittany A. Jaso, Mark J. Niciu, Nicolas D. Iadarola et al.
97 citations
Current antidepressants for major depressive disorder work through monoaminergic mechanisms and have a delayed onset and limited efficacy. Glutamate, the main excitatory neurotransmitter, is involved in depression's pathophysiology. Since ketamine, an NMDA receptor antagonist, showed rapid antidepressant effects in 2000, other NMDA receptor antagonists have been studied but with more modest effects. Some have advantages like oral administration and fewer side effects. This article reviews clinical evidence for glutamate receptor modulators: non-competitive NMDA antagonists (ketamine, memantine, dextromethorphan, AZD6765), NR2B-subunit antagonists (traxoprodil, MK-0657), glycine-site partial agonists (D-cycloserine, GLYX-13), and metabotropic glutamate receptor modulators (AZD2066, basimglurant). Preclinical targets like AMPA agonists and mGluR2/3 negative allosteric modulators are also discussed.
Journal of psychopharmacology (Oxford, England)
May 1, 2026
Brian O'Mahony, Colm Harrington, Andrew Harkin et al.
Psychedelic drugs are being studied as treatments for mental health conditions and used recreationally, but they can cause intense psychological distress known as a "bad trip," which may lead to emergency care or psychiatric hospitalization. Managing these episodes should prioritize non-pharmacological strategies, but when those are insufficient, medications that can safely end the psychedelic state are needed. This review systematically evaluates candidate abortive agents, including serotonin antagonists, antipsychotics, and certain anxiety and depression drugs, considering their mechanisms, safety, and suitability for acute care. The authors propose a provisional framework for pharmacological management and identify priorities for future research.