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Giovanni Martinotti

University of Chieti-Pescara, University of Hertfordshire

72 papers in the library · 1,635 citations · publishing 2003-2026

Papers

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686. Glutamate dysfunction in treatment-resistant depression: translational and clinical insights

The International Journal of Neuropsychopharmacology September 1, 2026 M di Nicola, M Pepe, G Martinotti

Abstract Background Treatment-resistant depression (TRD) represents a major clinical challenge and is associated with substantial symptom burden, functional impairment, and poor prognosis. Beyond traditional monoaminergic models, converging evidence indicates that dysfunction of the glutamatergic system plays a central role in the pathophysiology of TRD, contributing to impaired neuroplasticity...

Sex-specific vulnerabilities in cannabis-induced psychosis: A scoping review.

Asian Journal of Psychiatry July 8, 2026 Valerio Ricci, Domenico de Berardis, Giovanni Martinotti et al.

BACKGROUND Cannabis-induced psychosis presents complex sex-based disparities that challenge traditional epidemiological patterns. While males demonstrate higher cannabis use rates, emerging evidence reveals paradoxical vulnerability patterns where females may show heightened susceptibility to cannabis-related psychotic outcomes despite lower consumption rates. OBJECTIVE To map evidence for...

Treatment and management approaches for ketamine misuse: A systematic review of medical interventions

Journal of Substance Use and Addiction Treatment July 1, 2026 Alessio Mosca, Stefania Chiappini, Andrea Miuli et al.

INTRODUCTION: Ketamine, initially developed as an anesthetic and now increasingly prescribed for treatment-resistant depression, is also widely misused in recreational contexts. Chronic ketamine use, often leading to dependence, has been associated with severe physical complications, including ulcerative cystitis and gastrointestinal dysfunction, as well as cognitive, affective, and psychotic...

Mechanistic insights toward dissociating therapeutic from psychedelic effects: bridging the gap between psychedelic research and mental health care

Translational Psychiatry June 24, 2026 Mauro Pettorruso, Giacomo D’andrea, Antonio Inserra et al.

Clinical trials investigating psychedelic compounds for depression and anxiety-related disorders are yielding promising preliminary results. Psychedelics produce profound alterations in brain function—such as suppression of the default mode network and thalamocortical dysregulation—leading to intense subjective experiences including ego dissolution and mystical-type states. While often...

Intranasal esketamine in treatment-resistant depression with and without comorbid borderline personality disorder: A multicenter real-world longitudinal study.

Psychiatry Research June 16, 2026 Filippo Mazzoni, Fabiola Raffone, Arianna De Ciechi et al.

Borderline personality disorder (BPD) often occurs alongside treatment-resistant depression (TRD), but the impact of BPD on real-world outcomes with intranasal esketamine is unclear. Consecutive TRD outpatients initiating intranasal esketamine treatment at four Italian centres between 1 September 2024 and 30 September 2025 were enrolled in the study (n = 90): 45 with comorbid BPD and 45 without...

Functional outcomes with esketamine in treatment-resistant depression: A 6-month multicenter real-world study.

European psychiatry : the journal of the Association of European Psychiatrists June 10, 2026 Riccardo Guglielmo, Miriam Olivola, Alberto Inuggi et al.

Esketamine has demonstrated efficacy in treatment-resistant depression (TRD), but medium-term real-world functional outcomes remain understudied. This study described 6-month depressive symptoms and functional trajectories during routine esketamine treatment, focusing on functional outcomes and remission correlates. In this prospective multicenter study, 60 patients with TRD initiating...

Esketamine in treatment-resistant depression with and without comorbid borderline personality disorder: A real-world longitudinal study of suicidal ideation and self-harm.

Asian Journal of Psychiatry June 1, 2026 Fabiola Raffone, Filippo Mazzoni, Arianna De Ciechi et al. 3 citations

Suicidal ideation and deliberate self-harm are frequent and persistent in treatment-resistant depression (TRD), particularly when comorbid borderline personality disorder (BPD) is present. Real-world evidence on antisuicidal outcomes during intranasal esketamine in this population remains limited. In this multicentre prospective observational study, 90 outpatients with TRD received intranasal...

Functional recovery trajectories in cannabis-induced first-episode psychosis: The role of dissociative symptoms in the discrepancy between symptomatic improvement and functional outcomes.

Psychiatry Research May 25, 2026 Valerio Ricci, Andrea Paggi, Giovanni Martinotti et al.

Functional recovery in cannabis-induced first-episode psychosis (FEP) remains incompletely understood. Dissociative symptoms, frequently associated with cannabis use, may represent a key but underexplored determinant of functional trajectories. This prospective cohort study followed 72 patients meeting DSM-5 criteria for cannabis-induced psychotic disorder over 24 months. Functional recovery...

A Systematic Review of Clinical Phenomenology, Differential Diagnosis and Prognostic Outcomes of Substance-Induced Psychotic Disorders.

The International journal of social psychiatry April 26, 2026 Valerio Ricci, Giovanni Martinotti, Giuseppe Maina

Distinguishing substance-induced psychotic disorders (SIPD) from primary psychotic disorders with concurrent substance use remains a critical diagnostic challenge for treatment planning and prognostic counseling. To systematically review the clinical phenomenology of SIPD, identify distinguishing symptom patterns, and examine relationships between phenomenology and outcomes. A systematic search...

Epigenetic Mechanisms of Psychedelics in Addiction: Emerging Evidence and Therapeutic Potential

Clinical Neuropsychopharmacology and Addiction April 17, 2026 Antonio Inserra, Francesca Zoratto, Mauro Pettorruso et al.

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From substance-induced psychosis to schizophrenia: Predictors of treatment response and transition to chronic psychotic illness-A systematic review.

Schizophrenia Research March 24, 2026 Valerio Ricci, Stefania Chiappini, Giovanni Martinotti et al.

Substance-induced psychotic disorders (SIPDs) present significant clinical challenges with variable outcomes. While some patients achieve complete remission following substance cessation, others develop persistent symptoms requiring extended intervention. Understanding treatment response predictors is critical for optimizing clinical management and prognostic accuracy. Following PRISMA...

Narrative Experiences of Esketamine-Induced Dissociation in Patients with Treatment-Resistant Depression: A Qualitative Exploratory Study

Brain Sciences February 7, 2026 Miriam Olivola, Tiziano Prodi, Giada Versaci et al. 2 citations

Background/Objectives: Esketamine-related dissociation is a transient, pharmacologically induced altered state that differs from the trait-like pathological dissociation typically observed in trauma-related conditions. While most studies have quantified these effects using the Clinician-Administered Dissociative States Scale (CADSS), patients' subjective phenomenology and meaning-making remain...

Phenomenology of Hallucinations in Endogenous and Substance-Related Exogenous Psychoses.

Psychopathology 2026 Valerio Ricci, Massimiliano Aragona, Giuseppe Maina et al. 1 citation

Healthcare professionals encounter challenges in discerning endogenous and exogenous, drug-related, psychopathological phenomena. This study aimed to explore qualitative differences between hallucinations in schizophrenia and two forms of substance-related psychosis. These are substance-induced psychosis (SIP), which has an acute onset and is usually transient, and substance-related persistent...

Substance-Specific Treatment Responses and Resistance Patterns in Induced Psychoses: A Scoping Review of Antipsychotic Efficacy

Healthcare December 8, 2025 Valerio Ricci, Stefania Chiappini, Giovanni Martinotti et al.

Objective: To scope the available literature on antipsychotic treatment in substance-induced psychotic disorders, summarize evidence across substance categories, and highlight priorities for future research. Methods: This scoping review followed Arksey and O’Malley’s framework and PRISMA-ScR guidelines. A systematic search of PubMed, Scopus, Embase, PsycINFO, and Cochrane Library (January...

Anomalous self-experience in substance-induced and primary psychotic disorders: a cross-sectional comparative study using the EASE interview.

Annals of General Psychiatry November 25, 2025 Luisa de Risio, Alessio Mosca, Arianna Pasino et al.

Disturbances of the minimal self, or anomalous self-experiences (ASEs), are increasingly regarded as a core feature of primary psychotic disorders (PPDs). However, it remains unclear whether similar self-disorders are present in substance-induced psychosis (SIP), a condition that often mimics PPDs in its early stages. The study aims to compare ASEs between PPD and SIP using the EASE interview,...

Psychedelics and ketamine/esketamine in depressive disorders: biological mechanisms and associated neuroimaging and clinical changes.

Transl Psychiatry October 31, 2025 Giacomo D’andrea, Stefania Chiappini, Laura Ciavoni et al. 3 citations

Psychedelics and ketamine/esketamine in depressive disorders: biological mechanisms and associated neuroimaging and clinical changes.

Novel psychoactive substances (NPS) as a risk factor for psychosis: A systematic review of the literature

Neuroscience & Biobehavioral Reviews October 19, 2025 Alessio Mosca, Gianluca Mancusi, Stefania Chiappini et al. 6 citations

Novel psychoactive substances (NPS) are increasingly used by young individuals for their psychoactive effects and have been frequently associated with the emergence of psychotic symptoms and schizophrenia spectrum disorders. However, it remains unclear whether NPS use directly increases the risk of psychosis onset or whether individuals with a predisposition to psychosis are more likely to...

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

Introduction: Treatment-Resistant Depression (TRD) affects approximately 30–50% of patients with Major Depressive Disorder (MDD) who fail to respond to at least two adequate antidepressant trials. This condition presents substantial clinical and functional challenges, and no universally accepted treatment algorithm currently exists. Emerging therapeutic strategies, particularly glutamatergic...

Mentalization and Emotional-Cognitive Rigidity as predictors of esketamine's effects on Treatment-Resistant Depression: Findings from a prospective observational study.

Journal of Affective Disorders September 1, 2025 Miriam Olivola, Filippo Mazzoni, Barbara Tarantino et al. 8 citations

INTRODUCTION Treatment-Resistant Depression (TRD) remains a major challenge in the management of Major Depressive Disorder (MDD). Esketamine, the S-enantiomer of ketamine and a glutamatergic modulator, has been approved by the FDA and EMA for TRD in 2019. Beyond its rapid antidepressant effects, esketamine may enhance neuroplasticity, facilitating the reconnection with emotional and cognitive...

Effects of persistent cannabis use on depression, psychosis, and suicidality following cannabis‐induced psychosis: A longitudinal study

The American Journal on Addictions September 1, 2025 Valerio Ricci, Domenico de Berardis, Giovanni Martinotti et al.

AbstractBackground and ObjectivesCannabis use is associated with psychotic disorder onset and exacerbation. This study examines how continued cannabis use affects depressive symptoms, psychotic symptoms, and suicidal behaviors following cannabis‐induced first‐episode psychosis (FEP).MethodsSixty‐five participants (aged 16–50 years) with FEP were recruited from psychiatric inpatient facilities...

Endocannabinoids, depression, and treatment resistance: Perspectives on effective therapeutic interventions

Psychiatry Research August 18, 2025 Ilenia Rosa, L. Padula, Francesco Semeraro et al. 2 citations

Depression is a prevalent and heterogeneous disorder with significant personal and social consequences. The rise of treatment-resistant depression (TRD) challenges traditional approaches and underscores the need for a broader neurobiological perspective. When monoaminergic modulation proves insufficient, clinical guidelines increasingly turn to non-monoaminergic interventions such as...

631. PSILOCYBIN AND KETANSERIN VS RTMS IN TREATMENT-RESISTANT DEPRESSION: ENHANCING TOLERABILITY BY MITIGATING PSYCHEDELIC EFFECTS

The International Journal of Neuropsychopharmacology August 1, 2025 Giovanni Martinotti, Clara Cavallotto, Giacomo D’andrea et al.

Abstract Background Among the innovative treatments investigated for depression, psilocybin appears to play an extremely promising role, with several studies showing remission rates up to 70% in patients with treatment-resistant depression (TRD) treated with protocols involving a single or double dose administration [1,2]. Psilocybin is a psychedelic compound belonging to the tryptamine class,...

Effectiveness of repeated Esketamine nasal spray administration on anhedonic symptoms in treatment-resistant bipolar and unipolar depression: A secondary analysis from the REAL-ESK study group.

Psychiatry Research July 26, 2025 Giacomo D’andrea, Clara Cavallotto, Mauro Pettorruso et al. 16 citations

INTRODUCTION Anhedonia, defined as the diminished ability to experience or anticipate pleasure, is a core symptom of major depressive disorder (MDD) and bipolar depression (BD), and associated with depression severity, suicidality and poor treatment outcomes. Conventional antidepressants demonstrate limited efficacy against anhedonia. Esketamine nasal spray (ESK-NS) - a novel NMDA receptor...

Alexithymia and psychopathological dimensions in First-Episode Psychosis: Comparative patterns in natural cannabis versus synthetic cannabinoid users

Journal of Psychiatric Research June 19, 2025 Valerio Ricci, Ilenia di Muzio, Mancusi Gianluca et al. 2 citations

AIMS: This study aimed to investigate the differences in psychotic symptomatology, dissociative symptoms, alexithymia, and aberrant salience among three groups: non-cannabis users (NU), natural cannabis users (NC), and synthetic cannabinoid users (SCs). The study also explored the patterns of alexithymia and its associations with other psychopathological dimensions in these populations....