Journal of affective disorders
August 1, 2025
Morgan C H Cheng, Christine E Dri, Hana Ballum et al.
12 citations
Ketamine and esketamine produce rapid antidepressant effects in major depressive disorder and treatment-resistant depression, but their impact on patient-reported quality of life has been unclear. A systematic review of five studies found that both agents improve quality of life measures on scales such as the WHOQOL-BREF, Assessment of Quality of Life 8D, and EuroQol-5 Dimension-5 Layers, with statistically significant results. However, the studies had an overall moderate risk of bias and varied in the quality-of-life scales used and study duration. Further research should examine effects on specific quality-of-life domains.
Clinical neuropharmacology
June 19, 2026
Isabela Heroiu, Gia Han Le, Maria-Christina Sioufi et al.
Ketamine, an N-methyl-D-aspartate receptor antagonist, consistently and significantly reduced obsessive-compulsive disorder symptom severity by up to 50% to 60% across five studies, though the duration of effects ranged from a few hours to six weeks. Ketamine was generally well tolerated. The review included three randomized controlled trials and two open-label trials with variable routes of administration (intravenous, intramuscular, and oral) and dosing frequencies. Further research is needed to optimize ketamine treatment for sustained symptom reduction.
Pharmacopsychiatry
February 5, 2026
Tianyi Xu, Sabrina Wong, Gia Han Le et al.
Lysergic acid diethylamide and 3,4-methylenedioxymethamphetamine activate the 5-hydroxytryptamine 2B receptor, a pathway known to cause drug-induced valvular heart disease. This systematic review of 17 studies found no research on psilocybin, dimethyltryptamine, or mescaline. Both lysergic acid diethylamide and 3,4-methylenedioxymethamphetamine show high or moderate affinity for this receptor and promote signaling linked to fibrotic changes in heart valve tissue. In vivo studies confirm serotonin-induced valvulopathy, and chronic 3,4-methylenedioxymethamphetamine use has been associated with valve abnormalities in humans. No clinical cases of lysergic acid diethylamide-induced valvulopathy have been reported, but preclinical data suggest potential for fibrotic signaling under sustained exposure. Preliminary evidence supports the need for cardiac safety monitoring in psychedelic research.
Journal of affective disorders
February 1, 2026
Kayla M Teopiz, Sabrina Wong, Gia Han Le et al.
Reward processing disruptions in major depressive disorder (MDD) may relate to altered frontostriatal brain activity. Glutamatergic modulators might improve reward function. This systematic review examined 11 fMRI studies testing glutamatergic agents—ketamine (9 studies), nitrous oxide (1), and memantine (1)—on frontostriatal activity in people with MDD or healthy controls. Preliminary evidence suggests intravenous ketamine may alter functional connectivity in striatal regions, potentially relevant to improved reward function in treatment-resistant depression. More research is needed on how these modulators affect reward-related brain structures, the timing of effects, and baseline characteristics predicting antidepressant response.
Expert opinion on drug metabolism & toxicology
January 1, 2026
Yang Jing Zheng, Christine E Dri, Sabrina Wong et al.
Dextromethorphan/bupropion (DXM/BUP) received breakthrough FDA approval in August 2022 as a rapid-acting antidepressant. DXM/BUP is a noncompetitive NMDA receptor antagonist and sigma-1 receptor agonist, combined with bupropion, a norepinephrine/dopamine reuptake inhibitor and CYP2D6 inhibitor. DXM alone has long been misused due to its metabolism into the psychoactive metabolite dextrorphan (DXO). The article discusses the pharmacodynamics and pharmacokinetics of DXM and DXO, highlights the abuse potential of DXM alone, and presents preclinical, clinical, and pharmacovigilance findings that support reduced abuse liability of DXM/BUP. The formulation demonstrates clinically meaningful improvement within one week of initiation. Given its safety, efficacy, and novelty, this glutamatergic modulator is a promising candidate for global approval. Future research should examine its potential in bipolar depression and trauma-associated MDD.