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Clinical Neuropsychopharmacology and Addiction

ISSN 3083-5070

5 papers in the library · 2 citations · publishing 2025-2026

Papers

Novel perspectives for glutamatergic strategies, psychedelics and antipsychotic augmentation in Treatment Resistant Depression: A narrative review

Clinical Neuropsychopharmacology and Addiction September 25, 2025 Stefania Chiappini, Clara Cavallotto, Andrea Miuli et al. 2 citations

About 30–50% of patients with major depression do not respond to two or more antidepressant trials, a condition called treatment-resistant depression (TRD). A narrative review of 60 studies found that glutamatergic agents such as intravenous ketamine and intranasal esketamine consistently produce rapid and clinically meaningful reductions in depressive symptoms. Augmentation with atypical antipsychotics also helps partial responders. Psychedelic-assisted therapies show sustained antidepressant benefits and affect biomarkers like BDNF and inflammatory markers. The findings suggest a shift toward personalized, mechanism-driven treatments for TRD, with ketamine and esketamine offering rapid relief for acute high-risk cases and psychedelics remaining experimental but promising as adjunctive options.

Sex- and Age-Stratified Differences in Antidepressant Response to Intranasal Esketamine in Treatment-Resistant Depression: A Secondary Analysis of the REAL-ESK Study

Clinical Neuropsychopharmacology and Addiction June 25, 2026 Luca Persico, Giacomo D’andrea, Clara Cavallotto et al.

Intranasal esketamine substantially reduced depression severity in 210 patients with treatment-resistant depression treated in routine clinical practice. Depression scores improved markedly over three months, and men showed a modest advantage over women by the end of treatment, with lower depression ratings and higher rates of response and remission. Among patients under 65 years, sex differences were small and not statistically significant; among those 65 and older, men appeared to benefit more numerically, but this difference did not hold up after statistical correction and remains uncertain. Discontinuation rates and safety outcomes were similar between sexes. The authors call for future studies to examine hormonal, vascular, inflammatory, and other factors that might explain the observed sex differences.

Can Substance-Induced Psychoses (SIP) Shed Light on the Paradigm of Schizophrenia?

Clinical Neuropsychopharmacology and Addiction March 10, 2026 Filippo Maria Ferro, Alessio Mosca

Substance-induced psychoses may help uncover mechanisms behind psychotic disorders and clarify the phenomenological specifics of schizophrenia. Some patients do not fully recover after an episode, suggesting persistent psychotic trajectories distinct from both acute substance-induced psychosis and primary psychotic disorders. The concept of Substance-Related Exogenous Psychosis positions exogenous psychoses as related to, but not identical with, schizophrenia. Drawing on classical psychopathology and recent self-disorder research, substance-induced psychoses can serve as heuristic models for exploring psychosis genesis. Comparisons using the EASE interview show similarities but also differences: substance-induced psychoses involve more superficial, transient self-alterations, while schizophrenia involves deeper, structurally embedded disturbances. This framework aims to guide future longitudinal studies.

Ketamine-Related Deaths Registered in Scotland 2013–2024

Clinical Neuropsychopharmacology and Addiction January 4, 2026 Amira Guirguis, John Martin Corkery, Fabrizio Schifano

Ketamine-related deaths in Scotland rose twentyfold between 2013 and 2024, with 88 deaths recorded. Most decedents were male (81.8%), average age 35, and 84% of deaths were accidental. Polysubstance use was common: opioids (58%), stimulants (55%), benzodiazepines (48%), gabapentinoids (25%), and alcohol (22%) were often co-implicated. Acute drug use was the primary cause in 85% of cases. The upward trend mirrors increases elsewhere in the UK. Combining ketamine with opioids or benzodiazepines adds fatal risk via central nervous system depression. The findings underscore the need for clearer public health messaging, targeted harm reduction, and monitoring of misuse and prescribing trends.