GIANLUCA VITA

@irccsme.it

Neurologist
IRCCS Centro Neurolesi "Bonino-Pulejo", Messina, Italy Unit of Neurology, Department of Emergency, P.O. Piemonte,

GIANLUCA VITA


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https://researchid.co/vitagianluca

RESEARCH INTERESTS

neurology
12

Scopus Publications

Scopus Publications

  • Characterising alexithymia in individuals with functional motor disorders: a cross-sectional analysis of the Italian Registry of Functional Motor Disorders
    Giovanni Ostuzzi, Christian Geroin, Chiara Gastaldon, Federico Tedeschi, Francesca Maria Clesi, Giacomo Trevisan, Giovanni Bidello, Giovanni Vita, Enrico Marcuzzo, Angela Sandri, Luigi M Romito, Roberto Eleopra, Lucia Tesolin, Ilaria Franch, Mario Zappia, Alessandra Nicoletti, Benedetta Demartini, Veronica Nisticò, Nicola Modugno, Enrica Olivola, Andrea Pilotto, Alessandro Padovani, Giovanni Defazio, Tommaso Ercoli, Martina Petracca, Rosa De Micco, Carlo Dallocchio, Marcello Esposito, Roberto Erro, Eleonora Del Prete, Francesco Amaddeo, Corrado Barbui, Michele Tinazzi
    Journal of Neurology Neurosurgery and Psychiatry, 2025
    Background Alexithymia, a personality trait characterised by difficulty in identifying and expressing emotions, may contribute to the onset and clinical presentation of functional motor disorders (FMDs), although this association remains underexplored. Methods From the Italian Registry of FMDs, we selected individuals recruited between November 2011 and January 2023, diagnosed with FMD according to Gupta and Lang criteria and assessed for various neurological and psychological features with validated rating scales. The main statistical analysis included regression models using the Toronto Alexithymia Scale 20 items as an explanatory variable for a set of clinical measures, adjusting for sociodemographic factors and correcting for multiple testing. Results In a cohort of 483 individuals, 20.7% had possible alexithymia and 31.5% had definite alexithymia. Higher levels of alexithymia were strongly associated with increased severity of depression (β=0.31, p<0.001), anxiety (β=0.32, p<0.001), general psychological distress (β=−0.27, p<0.001), fatigue (β=0.05, p<0.001) and pain (β=0.32, p<0.001) and moderately associated with a slower onset of FMD (β=0.02, p=0.003). Subscale analyses revealed that difficulties identifying feelings contributed most to these associations. No significant association was observed with motor symptom severity. Conclusions Emotional processing difficulties of individuals with FMD and alexithymia might increase their vulnerability to mental health problems, pain and fatigue, possibly aggravating the overall prognosis. Further research is needed to elucidate the underlying mechanisms linking alexithymia to FMD and to explore the efficacy of interventions targeting emotional awareness and regulation in this population and to prevent long-term mental health burdens.
  • Efficacy and tolerability of antidepressants in individuals suffering from physical conditions and depressive disorders: network meta-analysis
    Beatrice De Luca, Andrea Canozzi, Carlotta Mosconi, Chiara Gastaldon, Davide Papola, Alessia Metelli, Federico Tedeschi, Francesco Amaddeo, Marianna Purgato, Marco Solmi, Corrado Barbui, Giovanni Vita, Giovanni Ostuzzi
    British Journal of Psychiatry, 2025
    BackgroundAntidepressants are effective for depression, but most evidence excludes individuals with comorbid physical conditions.AimsTo assess antidepressants’ efficacy and tolerability in individuals with depression and comorbid physical conditions.MethodsSystematic review and network meta-analysis of randomised controlled trials (RCTs). Co-primary outcomes were efficacy on depressive symptoms and tolerability (participants dropping out because of adverse events). Bias was assessed with the Cochrane Risk-of-Bias 2 tool and certainty of estimates with the Confidence in Network Meta-Analysis approach. A study protocol was registered in advance (https://osf.io/9cjhe/).ResultsOf the 115 included RCTs, 104 contributed to efficacy (7714 participants) and 82 to tolerability (6083 participants). The mean age was 55.7 years and 51.9% of participants were female. Neurological and cardiocirculatory conditions were the most represented (26.1% and 18.3% of RCTs, respectively). The following antidepressants were more effective than placebo: imipramine, nortriptyline, amitriptyline, desipramine, sertraline, paroxetine, citalopram, fluoxetine, escitalopram, mianserin, mirtazapine and agomelatine, with standardised mean differences ranging from −1.01 (imipramine) to −0.34 (escitalopram). Sertraline and paroxetine were effective for the largest number of ICD-11 disease subgroups (four out of seven). In terms of tolerability, sertraline, imipramine and nortriptyline were less tolerated than placebo, with relative risks ranging from 1.47 (sertraline) to 3.41 (nortriptyline). For both outcomes, certainty of evidence was ‘low’ or ‘very low’ for most comparisons.ConclusionAntidepressants are effective in individuals with comorbid physical conditions, although tolerability is a relevant concern. Selective serotonin reuptake inhibitors (SSRIs) have the best benefit–risk profile, making them suitable as first-line treatments, while tricyclics are highly effective but less tolerated than SSRIs and placebo.
  • Effectiveness of digital health interventions for chronic conditions management in European primary care settings: Systematic review and meta-analysis
    Elisa Ambrosi, Elisabetta Mezzalira, Federica Canzan, Chiara Leardini, Giovanni Vita, Giulia Marini, Jessica Longhini
    International Journal of Medical Informatics, 2025
    BACKGROUND: The past decade has seen rapid digitalization of healthcare, significantly transforming healthcare delivery. However, the impact of these technologies remains unclear, with notable gaps in evidence regarding their effectiveness, especially in primary care settings. OBJECTIVE: This systematic review assesses the effectiveness of digital health interventions versus interventions without digital components implemented over the last 10 years in European primary care settings for managing chronic diseases. METHODS: Following Cochrane guidelines, we conducted a systematic review with meta-analysis. We searched multiple databases for randomized controlled trials. Inclusion criteria encompassed studies on digital health interventions for chronic disease management in primary care settings in Europe, evaluating outcomes such as hospitalizations, quality of life, and clinical measures. Data extraction and quality assessment were independently conducted by two authors, with discrepancies resolved by a third author. The certainty of the evidence was judged according to the Grading of Recommendations, Assessment, Development, and Evaluation approach. RESULTS: From 9829 records, 23 studies were included, with most studies conducted in the UK and Spain. The most investigated conditions were type 2 diabetes and hypertension. Interventions mainly focused on patient monitoring, self-care education, and digital communication tools. The risk of bias was low to moderate for most studies. Meta-analyses showed no significant differences between digital health interventions and usual care for hospitalizations, depressive symptoms, anxiety, HbA1c, diastolic blood pressure, weight, or quality of life, except for a small improvement in systolic blood pressure. CONCLUSION: Digital health interventions have not yet demonstrated substantial benefits over traditional care for chronic disease management in European primary care. While some improvements were noted, particularly in systolic blood pressure, the impact remains limited. Further research is needed to enhance the effectiveness of digital health interventions, address current methodological limitations, and explore tailored approaches for both specific patient populations and multimorbid populations.
  • Systematic Review and Network Meta-Analysis: Efficacy and Safety of Antipsychotics vs Antiepileptics or Lithium for Acute Mania in Children and Adolescents
    Giovanni Vita, Viktor B. Nöhles, Giovanni Ostuzzi, Corrado Barbui, Federico Tedeschi, Fabiola H. Heuer, Amanda Keller, Melissa P. DelBello, Jeffrey A. Welge, Thomas J. Blom, Robert A. Kowatch, Christoph U. Correll
    Journal of the American Academy of Child and Adolescent Psychiatry, 2025
    ObjectiveTo compare second-generation antipsychotics (SGAs) and mood stabilizers (MSs) in youth with a bipolar disorder type I (BD-I) manic/mixed episode.MethodA systematic PubMed/Embase/PsycInfo literature search until December 31, 2023, for randomized trials of SGAs or MSs in patients ≤18 years of age with BD-I manic/mixed episode was conducted. The study included a network meta-analysis comparing treatments regarding mania symptoms and mania response (co-primary outcomes), and secondary efficacy and tolerability outcomes.ResultsEighteen studies (n = 2844, mean age = 11.74, female participants = 48.0%, mean study duration = 5.4 weeks) comparing 6 SGAs (aripiprazole, asenapine, olanzapine, quetiapine, risperidone, and ziprasidone) and 4 MSs (lithium, oxcarbazepine, topiramate, and valproate) were meta-analyzed. All 6 SGAs outperformed placebo in reducing manic symptomatology, including risperidone (standardized mean difference [SMD] = −1.18, 95% CI = −0.92, −1.45, Confidence in Network Meta-Analysis [CINeMA] = moderate confidence), olanzapine (SMD = −0.77, 95% CI = −0.36, −1.18, low confidence), aripiprazole (SMD = −0.67, 95% CI = −0.33, −1.01, moderate confidence), quetiapine (SMD = −0.60, 95% CI = −0.32, −0.87, high confidence), asenapine (SMD = −0.54, 95% CI = −0.19, −0.89, moderate confidence), and ziprasidone (SMD = −0.43, 95% CI = −0.17, 0.70, low confidence), whereas no mood stabilizer outperformed placebo. Concerning mania response, risperidone (RR = 2.58, 95% CI = 1.88, 3.54, low confidence), olanzapine (RR = 2.42, 95% CI = 1.33, 3.54, very low confidence), aripiprazole (RR = 2.05, 95% CI = 1.44, 2.92, low confidence), quetiapine (RR = 1.89, 95% CI = 1.45n 2.47, moderate confidence), asenapine (RR = 1.81, 95% CI = 1.28, 2.55, very low confidence) and lithium (RR = 1.35, 95% CI = 1.00, 1.83, p = .049, very low confidence) outperformed placebo, without superiority of other MSs vs placebo. Individually, risperidone was more efficacious in reducing manic symptomatology than all other comparators, except olanzapine and topiramate, yet with low/very low confidence, and was associated with increased prolactin and glucose. Pooled together, SGAs outperformed both placebo and MSs for mania symptom reduction (SMD = −0.68, 95% CI = −0.86, −0.51 and SMD = −0.61, 95% CI = −0.82, −0.40, moderate confidence), and mania response (RR = 1.85, 95% CI = 1.53, 2.24 and RR = 1.65, 95% CI = 1.33, 2.04, moderate confidence) without differences between MSs and placebo. There were no significant treatment−placebo differences for all-cause discontinuation, whereas lithium, ziprasidone, and oxcarbazepine were associated with more adverse event-related drop-outs than placebo. Most SGAs were associated with more sedation, weight gain, and metabolic issues vs placebo and MSs.ConclusionSGAs were more efficacious than placebo and MSs in treating acute mania symptoms, however, their use must be carefully weighed against important side effects. To compare second-generation antipsychotics (SGAs) and mood stabilizers (MSs) in youth with a bipolar disorder type I (BD-I) manic/mixed episode. A systematic PubMed/Embase/PsycInfo literature search until December 31, 2023, for randomized trials of SGAs or MSs in patients ≤18 years of age with BD-I manic/mixed episode was conducted. The study included a network meta-analysis comparing treatments regarding mania symptoms and mania response (co-primary outcomes), and secondary efficacy and tolerability outcomes. Eighteen studies (n = 2844, mean age = 11.74, female participants = 48.0%, mean study duration = 5.4 weeks) comparing 6 SGAs (aripiprazole, asenapine, olanzapine, quetiapine, risperidone, and ziprasidone) and 4 MSs (lithium, oxcarbazepine, topiramate, and valproate) were meta-analyzed. All 6 SGAs outperformed placebo in reducing manic symptomatology, including risperidone (standardized mean difference [SMD] = −1.18, 95% CI = −0.92, −1.45, Confidence in Network Meta-Analysis [CINeMA] = moderate confidence), olanzapine (SMD = −0.77, 95% CI = −0.36, −1.18, low confidence), aripiprazole (SMD = −0.67, 95% CI = −0.33, −1.01, moderate confidence), quetiapine (SMD = −0.60, 95% CI = −0.32, −0.87, high confidence), asenapine (SMD = −0.54, 95% CI = −0.19, −0.89, moderate confidence), and ziprasidone (SMD = −0.43, 95% CI = −0.17, 0.70, low confidence), whereas no mood stabilizer outperformed placebo. Concerning mania response, risperidone (RR = 2.58, 95% CI = 1.88, 3.54, low confidence), olanzapine (RR = 2.42, 95% CI = 1.33, 3.54, very low confidence), aripiprazole (RR = 2.05, 95% CI = 1.44, 2.92, low confidence), quetiapine (RR = 1.89, 95% CI = 1.45n 2.47, moderate confidence), asenapine (RR = 1.81, 95% CI = 1.28, 2.55, very low confidence) and lithium (RR = 1.35, 95% CI = 1.00, 1.83, p = .049, very low confidence) outperformed placebo, without superiority of other MSs vs placebo. Individually, risperidone was more efficacious in reducing manic symptomatology than all other comparators, except olanzapine and topiramate, yet with low/very low confidence, and was associated with increased prolactin and glucose. Pooled together, SGAs outperformed both placebo and MSs for mania symptom reduction (SMD = −0.68, 95% CI = −0.86, −0.51 and SMD = −0.61, 95% CI = −0.82, −0.40, moderate confidence), and mania response (RR = 1.85, 95% CI = 1.53, 2.24 and RR = 1.65, 95% CI = 1.33, 2.04, moderate confidence) without differences between MSs and placebo. There were no significant treatment−placebo differences for all-cause discontinuation, whereas lithium, ziprasidone, and oxcarbazepine were associated with more adverse event-related drop-outs than placebo. Most SGAs were associated with more sedation, weight gain, and metabolic issues vs placebo and MSs. SGAs were more efficacious than placebo and MSs in treating acute mania symptoms, however, their use must be carefully weighed against important side effects.
  • Efficacy and acceptability of long-acting antipsychotics in acutely ill individuals with schizophrenia-spectrum disorders: A systematic review and network meta-analysis
    Giovanni Vita, Demetrio Pollini, Andrea Canozzi, Davide Papola, Chiara Gastaldon, Christoph U. Correll, Corrado Barbui, Giovanni Ostuzzi
    Psychiatry Research, 2024
    To assess the effect of Long-acting injectable (LAI) antipsychotics in acutely ill patients, we systematically searched major databases for randomized controlled trials (RCTs) comparing LAIs with other LAIs, oral antipsychotics, or placebo in acutely symptomatic adults with schizophrenia-spectrum disorders. Data were analyzed with a random-effects network meta-analysis. Co-primary outcomes were efficacy (mean change in psychopathology rating scales) and acceptability (all-cause discontinuations) at study endpoint. Of 25 RCTs, 19 studies tested second-generation LAIs (SGA-LAIs) and six first-generation LAIs (FGA-LAIs). Due to a disconnected network, FGA-LAIs were analyzed separately, with poor data quality. The SGA-LAIs network included 8,418 individuals (males=63%, mean age=39.3 years). All SGA-LAIs outperformed placebo in reducing acute symptoms at study endpoint (median follow-up=13 weeks). They were more acceptable than placebo with the only exception of olanzapine, for which no differences with placebo emerged. Additionally, we distinguished between different LAI formulations of the same antipsychotic to explore potential pharmacokinetic differences. Most formulations outperformed placebo in the very short-term (2 weeks or less), regardless of the need for initial oral supplementation. SGA-LAIs are evidence-based treatments in acutely ill individuals with schizophrenia-spectrum disorders. Findings support the use of SGA-LAIs to manage psychopathology and improve adherence right from the acute phases of illness.
  • Treatment of Locally Advanced Rectal Cancer in the Era of Total Neoadjuvant Therapy: A Systematic Review and Network Meta-Analysis
    Giulia Turri, Giovanni Ostuzzi, Giovanni Vita, Valeria Barresi, Aldo Scarpa, Michele Milella, Renzo Mazzarotto, Andrea Ruzzenente, Corrado Barbui, Corrado Pedrazzani
    JAMA Network Open, 2024
    ImportanceTreatment of locally advanced rectal cancer (LARC) involves neoadjuvant chemoradiotherapy plus total mesorectal excision and adjuvant chemotherapy. However, total neoadjuvant therapy (TNT) protocols (ie, preoperative chemotherapy in addition to radiotherapy) may allow better adherence and early treatment of distant micrometastases and may increase pathological complete response (pCR) rates.ObjectiveTo assess the efficacy and tolerability of TNT protocols for LARC.Data SourcesMEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science Core Collection electronic databases and ClinicalTrials.gov for unpublished studies were searched from inception to March 2, 2024.Study SelectionRandomized clinical trials including adults with LARC who underwent rectal resection as a final treatment were included. Studies including nonoperative treatment (watch-and-wait strategy), treatments other than rectal resection, immunotherapy, or antiangiogenic agents were excluded. Among the initially identified studies, 2.9% met the selection criteria.Data Extraction and SynthesisTwo authors independently screened the records and extracted data. Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA)–compliant pairwise and network meta-analyses with a random-effects model were performed in a frequentist framework, and the certainty of evidence was assessed according to the confidence in network meta-analysis approach.Main Outcomes and MeasuresThe primary outcome was pCR, defined as the absence of residual tumor at pathological assessment after surgery. Secondary outcomes included tolerability, toxic effects, perioperative outcomes, and long-term survival.ResultsOf 925 records identified, 27 randomized clinical trials, including 13 413 adults aged 18 years or older (median age, 60.0 years [range, 42.0-63.5 years]; 67.2% male) contributed to the primary network meta-analysis. With regard to pCR, long-course chemoradiotherapy (L-CRT) plus consolidation chemotherapy (relative risk [RR], 1.96; 95% CI, 1.25-3.06), short-course radiotherapy (S-RT) plus consolidation chemotherapy (RR, 1.76; 95% CI, 1.34-2.30), and induction chemotherapy plus L-CRT (RR, 1.57; 95% CI, 1.09-2.25) outperformed standard L-CRT with single-agent fluoropyrimidine-based chemotherapy. Considering 3-year disease-free survival, S-RT plus consolidation chemotherapy (RR, 1.08; 95% CI, 1.01-1.14) and induction chemotherapy plus L-CRT (RR, 1.12; 95% CI, 1.01-1.24) outperformed L-CRT, in spite of an increased 5-year locoregional recurrence rate of S-RT plus consolidation chemotherapy (RR, 1.65; 95% CI, 1.03-2.63).Conclusions and RelevanceIn this systematic review and network meta-analysis, 3 TNT protocols were identified to outperform the current standard of care in terms of pCR rates, with good tolerability and optimal postoperative outcomes, suggesting they should be recognized as first-line treatments.
  • Efficacy and safety of long-acting injectable versus oral antipsychotics in the treatment of patients with early-phase schizophrenia-spectrum disorders: a systematic review and meta-analysis
    Giovanni Vita, Angelantonio Tavella, Giovanni Ostuzzi, Federico Tedeschi, Michele De Prisco, Rafael Segarra, Marco Solmi, Corrado Barbui, Christoph U. Correll
    Therapeutic Advances in Psychopharmacology, 2024
    Background: Long-acting injectable antipsychotics (LAIs) have advantages over oral antipsychotics (OAPs) in preventing relapse and hospitalization in chronically ill patients with schizophrenia-spectrum disorders (SSDs), but evidence in patients with first-episode/recent-onset, that is, early-phase-SSDs is less clear. Objectives: To assess the relative medium- and long-term efficacy and safety of LAIs versus OAPs in the maintenance treatment of patients with early-phase SSDs. Method: We searched major electronic databases for head-to-head randomized controlled trials (RCTs) comparing LAIs and OAPs for the maintenance treatment of patients with early-phase-SSDs. Design: Pairwise, random-effects meta-analysis. Relapse/hospitalization and acceptability (all-cause discontinuation) measured at study-endpoint were co-primary outcomes, calculating risk ratios (RRs) with their 95% confidence intervals (CIs). Subgroup analyses sought to identify factors moderating differences in efficacy or acceptability between LAIs and OAPs. Results: Across 11 head-to-head RCTs ( n = 2374, median age = 25.2 years, males = 68.4%, median illness duration = 45.8 weeks) lasting 13–104 (median = 78) weeks, no significant differences emerged between LAIs and OAPs for relapse/hospitalization prevention (RR = 0.79, 95%CI = 0.58–1.06, p = 0.13) and acceptability (RR = 0.92, 95%CI = 0.80–1.05, p = 0.20). The included trials were highly heterogeneous regarding methodology and patient populations. LAIs outperformed OAPs in preventing relapse/hospitalization in studies with stable patients (RR = 0.65, 95%CI = 0.45–0.92), pragmatic design (RR = 0.67, 95%CI = 0.54–0.82), and strict intent-to-treat approach (RR = 0.64, 95%CI = 0.52–0.80). Furthermore, LAIs were associated with better acceptability in studies with schizophrenia patients only (RR = 0.87, 95%CI = 0.79–0.95), longer illness duration (RR = 0.88, 95%CI = 0.80–0.97), unstable patients (RR = 0.89, 95%CI = 0.81–0.99) and allowed OAP supplementation of LAIs (RR = 0.90, 95%CI = 0.81–0.99). Conclusion: LAIs and OAPs did not differ significantly regarding relapse prevention/hospitalization and acceptability. However, in nine subgroup analyses, LAIs were superior to OAPs in patients with EP-SSDs with indicators of higher quality and/or pragmatic design regarding relapse/hospitalization prevention (four subgroup analyses) and/or reduced all-cause discontinuation (five subgroup analyses), without any instance of OAP superiority versus LAIs. More high-quality pragmatic trials comparing LAIs with OAPs in EP-SSDs are needed. Trial registration: CRD42023407120 (PROSPERO).
  • An umbrella review of candidate predictors of response, remission, recovery, and relapse across mental disorders
    Marco Solmi, Samuele Cortese, Giovanni Vita, Michele De Prisco, Joaquim Radua, Elena Dragioti, Ole Köhler-Forsberg, Nanna M. Madsen, Christopher Rohde, Luis Eudave, Claudia Aymerich, Borja Pedruzo, Victoria Rodriguez, Stella Rosson, Michel Sabé, Mikkel Hojlund, Ana Catalan, Beatrice de Luca, Michele Fornaro, Giovanni Ostuzzi, Corrado Barbui, Gonzalo Salazar-de-Pablo, Paolo Fusar-Poli, Christoph U. Correll
    Molecular Psychiatry, 2023
    We aimed to identify diagnosis-specific/transdiagnostic/transoutcome multivariable candidate predictors (MCPs) of key outcomes in mental disorders. We conducted an umbrella review (protocol link), searching MEDLINE/Embase (19/07/2022), including systematic reviews of studies reporting on MCPs of response, remission, recovery, or relapse, in DSM/ICD-defined mental disorders. From published predictors, we filtered MCPs, validating MCP criteria. AMSTAR2/PROBAST measured quality/risk of bias of systematic reviews/individual studies. We included 117 systematic reviews, 403 studies, 299,888 individuals with mental disorders, testing 796 prediction models. Only 4.3%/1.2% of the systematic reviews/individual studies were at low risk of bias. The most frequently targeted outcome was remission (36.9%), the least frequent was recovery (2.5%). Studies mainly focused on depressive (39.4%), substance-use (17.9%), and schizophrenia-spectrum (11.9%) disorders. We identified numerous MCPs within disorders for response, remission and relapse, but none for recovery. Transdiagnostic MCPs of remission included lower disease-specific symptoms (disorders = 5), female sex/higher education (disorders = 3), and quality of life/functioning (disorders = 2). Transdiagnostic MCPs of relapse included higher disease-specific symptoms (disorders = 5), higher depressive symptoms (disorders = 3), and younger age/higher anxiety symptoms/global illness severity/ number of previous episodes/negative life events (disorders = 2). Finally, positive trans-outcome MCPs for depression included less negative life events/depressive symptoms (response, remission, less relapse), female sex (response, remission) and better functioning (response, less relapse); for schizophrenia, less positive symptoms/higher depressive symptoms (remission, less relapse); for substance use disorder, marital status/higher education (remission, less relapse). Male sex, younger age, more clinical symptoms and comorbid mental/physical symptoms/disorders were poor prognostic factors, while positive factors included social contacts and employment, absent negative life events, higher education, early access/intervention, lower disease-specific and comorbid mental and physical symptoms/conditions, across mental disorders. Current data limitations include high risk of bias of studies and extraction of single predictors from multivariable models. Identified MCPs can inform future development, validation or refinement of prediction models of key outcomes in mental disorders.
  • Antidepressants for the treatment of depression in people with cancer
    Giovanni Vita, Beatrice Compri, Faith Matcham, Corrado Barbui, Giovanni Ostuzzi
    Cochrane Database of Systematic Reviews, 2023
    BACKGROUND: Major depression and other depressive conditions are common in people with cancer. These conditions are not easily detectable in clinical practice, due to the overlap between medical and psychiatric symptoms, as described by diagnostic manuals such as the Diagnostic and Statistical Manual of Mental Disorders (DSM) and International Classification of Diseases (ICD). Moreover, it is particularly challenging to distinguish between pathological and normal reactions to such a severe illness. Depressive symptoms, even in subthreshold manifestations, have a negative impact in terms of quality of life, compliance with anticancer treatment, suicide risk and possibly the mortality rate for the cancer itself. Randomised controlled trials (RCTs) on the efficacy, tolerability and acceptability of antidepressants in this population are few and often report conflicting results. OBJECTIVES: To evaluate the efficacy, tolerability and acceptability of antidepressants for treating depressive symptoms in adults (aged 18 years or older) with cancer (any site and stage). SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was November 2022. SELECTION CRITERIA: We included RCTs comparing antidepressants versus placebo, or antidepressants versus other antidepressants, in adults (aged 18 years or above) with any primary diagnosis of cancer and depression (including major depressive disorder, adjustment disorder, dysthymic disorder or depressive symptoms in the absence of a formal diagnosis). DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcome was 1. efficacy as a continuous outcome. Our secondary outcomes were 2. efficacy as a dichotomous outcome, 3. Social adjustment, 4. health-related quality of life and 5. dropouts. We used GRADE to assess certainty of evidence for each outcome. MAIN RESULTS: We identified 14 studies (1364 participants), 10 of which contributed to the meta-analysis for the primary outcome. Six of these compared antidepressants and placebo, three compared two antidepressants, and one three-armed study compared two antidepressants and placebo. In this update, we included four additional studies, three of which contributed data for the primary outcome. For acute-phase treatment response (six to 12 weeks), antidepressants may reduce depressive symptoms when compared with placebo, even though the evidence is very uncertain. This was true when depressive symptoms were measured as a continuous outcome (standardised mean difference (SMD) -0.52, 95% confidence interval (CI) -0.92 to -0.12; 7 studies, 511 participants; very low-certainty evidence) and when measured as a proportion of people who had depression at the end of the study (risk ratio (RR) 0.74, 95% CI 0.57 to 0.96; 5 studies, 662 participants; very low-certainty evidence). No studies reported data on follow-up response (more than 12 weeks). In head-to-head comparisons, we retrieved data for selective serotonin reuptake inhibitors (SSRIs) versus tricyclic antidepressants (TCAs) and for mirtazapine versus TCAs. There was no difference between the various classes of antidepressants (continuous outcome: SSRI versus TCA: SMD -0.08, 95% CI -0.34 to 0.18; 3 studies, 237 participants; very low-certainty evidence; mirtazapine versus TCA: SMD -4.80, 95% CI -9.70 to 0.10; 1 study, 25 participants). There was a potential beneficial effect of antidepressants versus placebo for the secondary efficacy outcomes (continuous outcome, response at one to four weeks; very low-certainty evidence). There were no differences for these outcomes when comparing two different classes of antidepressants, even though the evidence was very uncertain. In terms of dropouts due to any cause, we found no difference between antidepressants compared with placebo (RR 0.85, 95% CI 0.52 to 1.38; 9 studies, 889 participants; very low-certainty evidence), and between SSRIs and TCAs (RR 0.83, 95% CI 0.53 to 1.22; 3 studies, 237 participants). We downgraded the certainty of the evidence because of the heterogeneous quality of the studies, imprecision arising from small sample sizes and wide CIs, and inconsistency due to statistical or clinical heterogeneity. AUTHORS' CONCLUSIONS: Despite the impact of depression on people with cancer, the available studies were few and of low quality. This review found a potential beneficial effect of antidepressants against placebo in depressed participants with cancer. However, the certainty of evidence is very low and, on the basis of these results, it is difficult to draw clear implications for practice. The use of antidepressants in people with cancer should be considered on an individual basis and, considering the lack of head-to-head data, the choice of which drug to prescribe may be based on the data on antidepressant efficacy in the general population of people with major depression, also taking into account that data on people with other serious medical conditions suggest a positive safety profile for the SSRIs. Furthermore, this update shows that the usage of the newly US Food and Drug Administration-approved antidepressant esketamine in its intravenous formulation might represent a potential treatment for this specific population of people, since it can be used both as an anaesthetic and an antidepressant. However, data are too inconclusive and further studies are needed. We conclude that to better inform clinical practice, there is an urgent need for large, simple, randomised, pragmatic trials comparing commonly used antidepressants versus placebo in people with cancer who have depressive symptoms, with or without a formal diagnosis of a depressive disorder.
  • Candidate diagnostic biomarkers for neurodevelopmental disorders in children and adolescents: a systematic review
    Samuele Cortese, Marco Solmi, Giorgia Michelini, Alessio Bellato, Christina Blanner, Andrea Canozzi, Luis Eudave, Luis C. Farhat, Mikkel Højlund, Ole Köhler‐Forsberg, Douglas Teixeira Leffa, Christopher Rohde, Gonzalo Salazar de Pablo, Giovanni Vita, Rikke Wesselhoeft, Joanna Martin, Sarah Baumeister, Natali S. Bozhilova, Christina O. Carlisi, Virginia Carter Leno, Dorothea L. Floris, Nathalie E. Holz, Eline J. Kraaijenvanger, Seda Sacu, Isabella Vainieri, Giovanni Ostuzzi, Corrado Barbui, Christoph U. Correll
    World Psychiatry, 2023
    Neurodevelopmental disorders – including attention‐deficit/hyperactivity disorder (ADHD), autism spectrum disorder, communication disorders, intellectual disability, motor disorders, specific learning disorders, and tic disorders – manifest themselves early in development. Valid, reliable and broadly usable biomarkers supporting a timely diagnosis of these disorders would be highly relevant from a clinical and public health standpoint. We conducted the first systematic review of studies on candidate diagnostic biomarkers for these disorders in children and adolescents. We searched Medline and Embase + Embase Classic with terms relating to biomarkers until April 6, 2022, and conducted additional targeted searches for genome‐wide association studies (GWAS) and neuroimaging or neurophysiological studies carried out by international consortia. We considered a candidate biomarker as promising if it was reported in at least two independent studies providing evidence of sensitivity and specificity of at least 80%. After screening 10,625 references, we retained 780 studies (374 biochemical, 203 neuroimaging, 133 neurophysiological and 65 neuropsychological studies, and five GWAS), including a total of approximately 120,000 cases and 176,000 controls. While the majority of the studies focused simply on associations, we could not find any biomarker for which there was evidence – from two or more studies from independent research groups, with results going into the same direction – of specificity and sensitivity of at least 80%. Other important metrics to assess the validity of a candidate biomarker, such as positive predictive value and negative predictive value, were infrequently reported. Limitations of the currently available studies include mostly small sample size, heterogeneous approaches and candidate biomarker targets, undue focus on single instead of joint biomarker signatures, and incomplete accounting for potential confounding factors. Future multivariable and multi‐level approaches may be best suited to find valid candidate biomarkers, which will then need to be validated in external, independent samples and then, importantly, tested in terms of feasibility and cost‐effectiveness, before they can be implemented in daily clinical practice.
  • Continuing, reducing, switching, or stopping antipsychotics in individuals with schizophrenia-spectrum disorders who are clinically stable: a systematic review and network meta-analysis
    Giovanni Ostuzzi, Giovanni Vita, Federico Bertolini, Federico Tedeschi, Beatrice De Luca, Chiara Gastaldon, Michela Nosé, Davide Papola, Marianna Purgato, Cinzia Del Giovane, Christoph U Correll, Corrado Barbui
    Lancet Psychiatry, 2022
  • Oral and long-acting antipsychotics for relapse prevention in schizophrenia-spectrum disorders: a network meta-analysis of 92 randomized trials including 22,645 participants
    Giovanni Ostuzzi, Federico Bertolini, Federico Tedeschi, Giovanni Vita, Paolo Brambilla, Lorenzo del Fabro, Chiara Gastaldon, Davide Papola, Marianna Purgato, Guido Nosari, Cinzia Del Giovane, Christoph U. Correll, Corrado Barbui
    World Psychiatry, 2022