Journal of affective disorders
December 15, 2024
Giacomo d'Andrea, Andrea Miuli, Mauro Pettorruso et al.
6 citations
In patients with treatment-resistant depression, combining vortioxetine with esketamine nasal spray reduces depressive symptoms as effectively as the standard combination of an SSRI or SNRI with esketamine. The vortioxetine combination also showed a larger reduction in emotional blunting after three months and had fewer treatment-emergent side effects. These findings come from a post-hoc analysis of twenty patients, ten in each group. The authors suggest the vortioxetine-plus-esketamine regimen may be a valuable alternative, but they call for larger randomized controlled trials to confirm the results.
Psychiatry International
September 20, 2024
Alessio Mosca, Stefania Chiappini, Andrea Miuli et al.
5 citations
Piperazines, synthetic compounds with stimulant and hallucinogenic effects, are linked to acute psychotic episodes. A systematic review of 4 studies found that piperazine abuse frequently triggers symptoms such as paranoia, auditory, and visual hallucinations. The compounds' complex polyreceptor action may explain these effects, similar to other novel psychoactive substances. Recovery is common after cessation and treatment, but data on long-term outcomes are limited. Further research into piperazine abuse and specific treatment protocols for substance-induced psychosis is needed.
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.
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.
Translational Psychiatry
June 24, 2026
Mauro Pettorruso, Giacomo D’andrea, Antonio Inserra et al.
Emerging clinical and preclinical evidence suggests that the therapeutic benefits of psychedelics for depression and anxiety may be separable from their consciousness-altering effects. Psychedelics produce profound brain changes, including suppression of the default mode network, leading to intense subjective experiences such as ego dissolution. These effects require extensive preparation and integration, exclude individuals with certain psychiatric vulnerabilities, and raise scalability concerns. Pharmacological strategies like serotonin 2A receptor antagonism and development of biased psychedelic analogues might retain therapeutic efficacy without psychedelic experiences. Preclinical data indicate that downstream molecular and network-level mechanisms could mediate therapeutic effects independently of subjective states. Confirming this dissociation could enable more scalable, accessible treatments for broader psychiatric populations.
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.