International Journal of Molecular Sciences
September 23, 2018
Domenico de Berardis, Michele Fornaro, Alessandro Valchera et al.
171 citations
Suicide remains difficult to predict despite advances in neuroscience. The World Health Organization reports one million suicide deaths annually, with one every 40 seconds. Recent genomic studies suggest genetics influence suicide risk. Combining genomic and clinical assessments has identified biomarkers for suicidal ideation involved in neural connectivity, mood, and immune response, including the mammalian target of rapamycin (mTOR) signaling pathway. This provides a neurobiological basis for drugs like ketamine, an NMDA antagonist, which has shown rapid antidepressant and anti-suicidal effects. This review examines preclinical and clinical evidence for ketamine's efficacy in treating suicidal ideation in mood disorders, addressing the neurobiological processes of suicide and potential therapeutics.
Frontiers in Psychiatry
November 20, 2017
Laura Orsolini, Gabriele Duccio Papanti, Domenico de Berardis et al.
99 citations
Hallucinogen-persisting perception disorder (HPPD) is a syndrome of prolonged or recurring perceptual symptoms resembling acute hallucinogen effects. It has been linked to LSD, cannabis, MDMA, psilocybin, mescaline, and psychostimulants, and more recently to novel psychoactive substances. Symptoms are mainly visual, including geometric pseudo-hallucinations, haloes, flashes of light, motion-perception deficits, afterimages, and micropsia, though depressive and thought disorders may co-occur. First described in 1954, HPPD was formally recognized as a syndrome in the DSM-IV-TR in 2000. Its neural substrates, risk factors, and causes remain largely unknown. This mini review surveys psychopathological bases, etiological hypotheses, and psychopharmacological approaches, including associations with novel substances, based on a literature search of PubMed/Medline, Google Scholar, and Scopus without time restrictions.
Annals of General Psychiatry
November 26, 2023
Giuseppe Maina, Marina Adami, Giuseppe Ascione et al.
56 citations
A Delphi panel of 60 Italian psychiatrists found wide variation in how treatment-resistant depression (TRD) is managed in Italy, highlighting a need for standardized strategies and treatments specifically approved for TRD. High consensus emerged on adding lithium or antipsychotics as augmentation therapies and on the need for long-term maintenance therapy. Esketamine nasal spray was identified as the best option for TRD patients, with agreement that it can be administered in a community outpatient setting given appropriate educational support for patients.
Frontiers in Psychiatry
November 20, 2019
Laura Orsolini, Stefania Chiappini, Duccio Papanti et al.
41 citations
The spread of novel psychoactive substances (NPS), especially among young people, raises concerns about psychosis linked to synthetic drugs. These 'new psychoses' differ clinically from classical psychosis. This mini-review synthesizes clinical and psychopathological features of NPS-induced psychoses and their treatment, based on a PubMed/Medline search for synthetic cannabinoids and cathinones. It contrasts classical psychoses with NPS-induced ones and offers therapeutic guidelines for clinicians in addiction psychiatry.
Current Topics in Medicinal Chemistry
January 31, 2020
Domenico de Berardis, Carmine Tomasetti, Maurizio Pompili et al.
38 citations
Abnormalities in glutamatergic neurotransmission are hypothesized to play a role in mood disorders, prompting investigation of NMDA receptor modulators for Major Depressive Disorder (MDD). Intranasal esketamine, an NMDA receptor antagonist, has been developed for treatment-resistant depression (TRD) and for rapidly reducing depressive symptoms, including suicidal ideation, in MDD patients at imminent suicide risk. A systematic review of literature up to October 2019 found that intravenous esketamine elicits rapid and sustained antidepressant effects in refractory patients. Phase II studies showed intranasal esketamine had rapid onset and persistent efficacy in TRD and MDD patients at suicide risk, though phase III data had discrepancies.
Frontiers in Psychiatry
May 22, 2018
Laura Orsolini, Michela Ciccarese, Duccio Papanti et al.
25 citations
A new 'psychedelic trend' has emerged, driven by psychonauts who consume a variety of novel psychoactive substances (NPS) from animals. This review identifies several species—including ants, amphibians, and fish—that possess psychoactive properties and are abused recreationally. Routes of administration vary by animal, substance, metabolism, toxicity, and cultural context. Online access to these animals is facilitated through tourism-related search terms such as 'frog trip' and 'religious trip.' The review combines online psychonaut reports with literature searches from PubMed/Medline and Google Scholar to provide an overview of commonly abused 'psychedelic animals.'
Psychiatry Research
July 26, 2025
G. D’andrea, C. Cavallotto, M. Pettorruso et al.
16 citations
Anhedonia, the reduced ability to experience pleasure, is a core symptom of both unipolar and bipolar depression that often responds poorly to standard antidepressants. In a real-world observational study of 253 treatment-resistant patients (199 with unipolar depression, 54 with bipolar depression), repeated doses of esketamine nasal spray added to ongoing medication significantly reduced anhedonia over three months. The effect was distinct from overall mood improvement. At three months, 51.92% of bipolar and 38% of unipolar patients showed at least a 50% reduction in anhedonia scores. Dropout rates were low (around 13–14%), and manic switches were rare. The findings suggest esketamine has a targeted, transdiagnostic anti-anhedonic effect.
European Psychiatry
March 1, 2016
Laura Orsolini, Alessandro Valchera, Duccio Papanti et al.
3 citations
Hallucinogen Persisting Perception Disorder (HPPD) is a syndrome marked by prolonged or recurring perceptual symptoms similar to acute hallucinogen effects, associated with substances like LSD, cannabis, MDMA, psilocybin, and mescaline. Symptoms mainly involve visual disturbances such as geometric pseudo-hallucinations, halos, flashes of light, motion-perception deficits, afterimages, and micropsy, though depressive and thought disorders may co-occur. First described in 1954, HPPD was formally established as a syndrome in the DSM-IV-TR in 2000. The neuronal substrate, risk factors, etiology, and pathogenesis remain unknown and under investigation. This critical review covers psychopathological bases, etiological hypotheses, and psychopharmacological approaches, presenting a case report and offering practical clinical recommendations.
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.
Preprints.org
April 29, 2026
Stefano Marini, Domenico de Berardis
preprint
Psychedelic drugs, both natural and synthetic, act on serotonin receptors and may enhance cognition, brain connectivity, neuroplasticity, and neuronal regeneration. Autism spectrum disorder involves social communication difficulties and repetitive behaviors, with no approved drugs for core symptoms. Current treatments for co-occurring conditions often have uncertain efficacy and tolerability. This review reports studies indicating that psychedelics could be therapeutically useful for some autism-related symptoms, suggesting a potential role in treatment.
Mental Wellness
April 21, 2026
Mohsen Khosravi, Domenico de Berardis, Massimo Tusconi
A systematic review and meta-analysis of 13 clinical trials with 606 participants found no statistically significant overall antidepressant effect of psilocybin-assisted psychotherapy for major depressive disorder and treatment-resistant depression. The pooled standardized mean difference was -0.79 with a 95% confidence interval from -3.98 to 2.40, and extreme heterogeneity across studies was observed. The type of control group accounted for most of the variation between studies, with waitlist and low-dose comparators exaggerating effect sizes. Session frequency moderated outcomes, with 2 to 5 sessions yielding larger effects and more intensive protocols reducing benefit. Psilocybin's antidepressant efficacy appears highly context-dependent rather than universally robust.