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.
The International Journal of Neuropsychopharmacology
February 1, 2025
Clara Cavallotto, Giacomo D’andrea, Andrea Miuli et al.
1 citation
In patients with treatment-resistant depression, combining the antidepressant vortioxetine with esketamine nasal spray was as effective as the standard combination of an SSRI or SNRI with esketamine in reducing depressive symptoms over three months. The vortioxetine combination showed a larger effect in reducing emotional blunting and was linked to fewer treatment-emergent side effects, including dissociative symptoms. These findings suggest vortioxetine plus esketamine may be a valuable alternative, though larger randomized trials are needed to confirm the results.
The International Journal of Neuropsychopharmacology
August 1, 2025
Giovanni Martinotti, Clara Cavallotto, G D’andrea et al.
Psilocybin, a psychedelic compound that acts on serotonin receptors, shows promise for treatment-resistant depression, with remission rates up to 70% in some studies. The antidepressant and psychedelic effects may be separable, with the latter linked to 5-HT2A receptors. By co-administering the 5-HT2A antagonist ketanserin, psilocybin's hallucinogenic effects can be minimized, reducing bias from the mystical experience and improving clinical feasibility. A proposed study will randomly assign 68 treatment-resistant depression patients to receive either non-psychedelic psilocybin (two 25 mg doses, preceded by ketanserin) or accelerated repetitive transcranial magnetic stimulation (arTMS). Outcomes will be compared at day 60 using psychometric tests, EEG, and fMRI.