Silvana Bertella

Scopus Publications

Patterns of response to methylphenidate administration in children with adhd: A personalized medicine approach through clustering analysis
Silvia Grazioli, Eleonora Rosi, Maddalena Mauri, Alessandro Crippa, Federica Tizzoni, Arianna Tarabelloni, Filippo Maria Villa, Federica Chiapasco, Maria Reimers, Erika Gatti, Silvana Bertella, Massimo Molteni, Maria Nobile
Children, 2021
Individual responses to methylphenidate (MPH) can significantly differ in children with attention-deficit/hyperactivity disorder (ADHD) in terms of the extent of clinical amelioration, optimal dosage needed, possible side effects, and short- and long-term duration of the benefits. In the present repeated-measures observational study, we undertook a proof-of-concept study to determine whether clustering analysis could be useful to characterize different clusters of responses to MPH in children with ADHD. We recruited 33 children with ADHD who underwent a comprehensive clinical, cognitive, and neurophysiological assessment before and after one month of MPH treatment. Symptomatology changes were assessed by parents and clinicians. The neuropsychological measures used comprised pen-and-paper and computerized tasks. Functional near-infrared spectroscopy was used to measure cortical hemodynamic activation during an attentional task. We developed an unsupervised machine learning algorithm to characterize the possible clusters of responses to MPH in our multimodal data. A symptomatology improvement was observed for both clinical and neuropsychological measures. Our model identified distinct clusters of amelioration that were related to symptom severity and visual-attentional performances. The present findings provide preliminary evidence that clustering analysis can potentially be useful in identifying different responses to MPH in children with ADHD, highlighting the importance of a personalized medicine approach within the clinical framework.
Eye movement desensitization and reprocessing: The state of the art of efficacy in children and adolescent with post traumatic stress disorder
Martina Manzoni, Isabel Fernandez, Silvana Bertella, Federica Tizzoni, Erica Gazzola, Massimo Molteni, Maria Nobile
Journal of Affective Disorders, 2021
BACKGROUND PTSD in youth is more common and debilitating than it was previously thought. This untreated condition is highly correlated to critical mental health condition, such as depression, anxiety disruptive-behaviours, and substance use disorders. Despite the growing number of studies investigating Eye Movement Desensitization and Reprocessing (EMDR) treatment for posttraumatic stress disorder (PTSD) in childhood and adolescent, results have not been systematically revised since 2017. The aim of this work is to systematically reviewed all randomized controlled trials (RCTs) evaluating the effect of EMDR on PTSD symptoms in children and adolescent and asses whether EMDR therapy was effective to improve anxious and/or depressive symptoms. METHODS In a short series of articles, we will review the efficacy of EMDR on children and adolescent with PTSD and comorbid symptoms. The present brief review will focus on randomized controlled trials with an EMDR group condition compared to a control group published until January 2020. RESULTS eight studies (n = 150) met our inclusion criteria. Preliminary analyses showed that EMDR has a comparable efficacy to cognitive behavior therapy (CBT) in reducing PTSD, anxiety symptoms, depressive symptoms and was superior to waitlist/placebo condition. Moreover EMDR seems to be more effective in a shorter period of time. CONCLUSION despite the small number of studies, the preliminary results suggest that EMDR therapy could be an effective treatment for children and adolescent with PTSD and anxious and/or depressive symptoms. Further research is needed to support these results.
Hemodynamic and behavioral peculiarities in response to emotional stimuli in children with attention deficit hyperactivity disorder: An fNIRS study
Maddalena Mauri, Silvia Grazioli, Alessandro Crippa, Andrea Bacchetta, Uberto Pozzoli, Silvana Bertella, Erika Gatti, Eleonora Maggioni, Eleonora Rosi, Vaibhav Diwadkar, Paolo Brambilla, Massimo Molteni, Maria Nobile
Journal of Affective Disorders, 2020
BACKGROUND Children with attention deficit hyperactivity disorder (ADHD) exhibit behavioral inhibition deficits, which often lead to emotional dysregulation (ED) affecting individual ability to control emotions and behavioral responses. In ADHD, ED is associated with poor outcomes and comorbidities, with both externalizing and internalizing disorders. This work aims to evaluate sensitivity to emotional stimuli in children with ADHD using functional Near Infrared Spectroscopy (fNIRS). METHODS During frontal fNIRS recording, 20 children with ADHD and 25 typically developing (TD) peers performed a visual continuous performance task with stimuli of different emotional content (i.e., positive, negative, neutral, and control stimuli without emotional content). This is a cognitive task designed to evaluate the ability to recognize emotional stimuli and to deal with emotional interference. RESULTS The ADHD sample showed more variability in response time to stimuli and more false alarms compared to TD group. fNIRS data showed between-group differences in right prefrontal and frontal cortices, with wider hemoglobin concentration changes in the TD group, during positive, negative, and neutral conditions. LIMITATIONS Owing to the limited possibility of near infrared light to penetrate tissue, fNIRS can only measure cortical activations, while it would be of interest to identify the subcortical areas linked to emotional processing, too. CONCLUSIONS Findings suggest the presence of emotional processing deficits in children with ADHD, as suggested by poor performances on the e-CPT task, and of peculiar sensitivity to emotional stimuli, linked to atypical hemodynamics of right prefrontal and frontal areas.
Emerging drugs for the treatment of attention-deficit hyperactivity disorder (ADHD)
Marco Pozzi, Silvana Bertella, Erika Gatti, Gabriëlla G. A. M. Peeters, Carla Carnovale, Stefania Zambrano, Maria Nobile
Expert Opinion on Emerging Drugs, 2020
Introduction Attention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder affecting up to 5.3% of children and 2.5% of adults depending on the country considered. Current pharmacological treatments for ADHD are based on stimulant or non-stimulant medications, targeting dopaminergic and noradrenergic systems in the frontal cortex and dopaminergic system in the basal ganglia. These drugs are effective and safe for the majority of patients, whereas about 20% of treated patients do not tolerate current therapies or experience insufficient efficacy. The adequate treatment of ADHD is necessary to allow a proper social placement and prevent the acquisition of additional, more severe, comorbidities. Areas covered We conducted a review of the scientific literature and of unpublished/ongoing clinical trials to summarize the advances made in the last 10 years (2010–2020) for the pharmacological treatment of ADHD. We found many pharmacological mechanisms beyond dopaminergic and noradrenergic ones have been investigated in patients. Expert opinion Some emerging drugs for ADHD may be promising as add-on treatment especially in children, amantadine to enhance cognitive functions and tipepidine for hyperactivity/impulsivity. Stand-alone emerging treatments for ADHD include viloxazine and dasotraline, which will soon have more clinical data available to support market access requests.
Persistence in therapy with risperidone and aripiprazole in pediatric outpatients: A 2-year naturalistic comparison
Marco Pozzi, Simone Pisano, Silvana Bertella, Annalisa Capuano, Renata Rizzo, Stefania Antoniazzi, Fabiana Auricchio, Carla Carnovale, Dario Cattaneo, Carmen Ferrajolo, Marta Gentili, Giuseppe Guastella, Elisa Mani, Concetta Rafaniello, Maria Pia Riccio, Maria Grazia Scuderi, Serena Sperandeo, Liberata Sportiello, Laura Villa, Sonia Radice, Emilio Clementi, Francesco Rossi, Antonio Pascotto, Renato Bernardini, Massimo Molteni, Carmela Bravaccio
Journal of Clinical Psychiatry, 2016
OBJECTIVE The practical effectiveness of second-generation antipsychotics in children and adolescents is an understudied issue. It is a crucial area of study, though, because such patients are often treated for long-lasting disorders. METHODS We carried out a 24-month (March 2012-March 2014) observational study on an unselected population of pediatric outpatients treated with risperidone, aripiprazole, olanzapine, or quetiapine aiming to (1) describe drug use, (2) compare post hoc the discontinuation rates due to specific causes and dose adjustments by Kaplan-Meier analyses between drugs, and (3) analyze predictors influencing these outcomes by Cox multivariate models. RESULTS Among 184 pediatric patients, 77% patients were prescribed risperidone, and 18% were prescribed aripiprazole. Olanzapine or quetiapine were scantly used; therefore, they were excluded from analyses. Risperidone was prevalent in younger, male patients with disruptive behavioral disorders; aripiprazole, in patients with tic disorders. Overall, discontinuations occurred mostly in the first 6 months, and, at 24 months, the discontinuation numbers were similar between users of risperidone and aripiprazole (41.5% vs 39.4%). In univariate analyses, dose reduction was higher for aripiprazole (P = .033). Multivariate analyses yielded the following predictors: for all-cause discontinuation, baseline severity (hazard ratio [HR] = 1.48, P = .001) and dose increase (HR = 3.55, P = .001); for patient-decided discontinuation, dose change (increase: HR = 6.43, P = .004; reduction: HR = 7.89, P = .049) and the presence of concomitant drugs (HR = 4.03, P = .034), while autistic patients discontinued less (HR = 0.23, P = .050); for clinician-decided discontinuation due to adverse drug reactions, baseline severity (HR = 1.96, P = .005) and dose increase (HR = 5.09, P = .016); for clinician-decided discontinuation due to inefficacy, baseline severity (HR = 2.88, P = .014) and the use of aripiprazole (HR = 5.55, P = .013); for dose increase, none; for dose reduction, the occurrence of adverse drug reactions (HR = 4.74, P = .046), while dose reduction was less probable in autistic patients (HR = 0.22, P = .042). CONCLUSIONS The findings of this study show a similarity between the overall effectiveness of risperidone and aripiprazole in a real-life pediatric outpatient setting.
Therapeutic drug monitoring of second-generation antipsychotics in pediatric patients: An observational study in real-life settings
Marco Pozzi, Dario Cattaneo, Sara Baldelli, Serena Fucile, Annalisa Capuano, Carmela Bravaccio, Liberata Sportiello, Silvana Bertella, Fabiana Auricchio, Renato Bernardini, Carmen Ferrajolo, Giuseppe Guastella, Elisa Mani, Carla Carnovale, Simone Pisano, Concetta Rafaniello, Maria Pia Riccio, Renata Rizzo, Maria Grazia Scuderi, Serena Sperandeo, Laura Villa, Antonio Pascotto, Massimo Molteni, Francesco Rossi, Sonia Radice, Emilio Clementi
European Journal of Clinical Pharmacology, 2016
PurposeAvailable guidelines on therapeutic drug monitoring of second-generation antipsychotics were designed for adults; therefore, they cannot be transferred as such in pediatric patients, who may have different drug absorption, distribution, metabolism, and elimination. Moreover, available tools that guide dosing in neuropsychiatric pediatric patients are scant, leading to the possibility of reduced efficacy and/or increased risks of toxicity. Here we describe the results of observational therapeutic drug monitoring conducted in three pediatric neuropsychiatry units across Italy in 2012–2014, with the following aims: (1) to describe the distribution of plasma concentrations of second-generation antipsychotics in our pediatric patients and (2) to identify clinical covariates associated with plasma drug levels.MethodsFive hundred fifty-six plasma trough concentrations of the second-generation antipsychotics risperidone (plus 9-hydroxy-risperidone), aripiprazole, olanzapine, and quetiapine were measured from 172 pediatric outpatients overall. The distribution of drug concentrations was described and correlated with drug doses and clinical variables.ResultsRisperidone plasma levels were lower than in adults (median 13.6 ng/ml), with a high inter-patient (78.9 %) but lower intra-patient (34.2 %) variability. In multiple regression analyses, risperidone plasma levels depended only on drug dose (p < 0.001). Aripiprazole plasma levels were similar to those described in adults (median 165.8 ng/ml) and were widely distributed, with an inter-patient variability of 81.1 %, while the intra-patient variability was much lower (29.3 %). Multiple regression analyses indicated that aripiprazole plasma levels were influenced by the daily doses (p < 0.001) and by the number of concomitant drugs (p < 0.01).ConclusionOur study described the distribution of plasma levels of SGAs in a real-life setting involving pediatric patients, significantly increasing the amount of available data for this fragile population. If confirmed in larger dataset, these data may contribute to the definition of optimal therapeutic window for risperidone and aripiprazole plasma levels in pediatric patients.
Second generation antipsychotics in ‘real-life’ paediatric patients. Adverse drug reactions and clinical outcomes of drug switch
Concetta Rafaniello, Marco Pozzi, Simone Pisano, Carmen Ferrajolo, Silvana Bertella, Liberata Sportiello, Carla Carnovale, Maria Giuseppa Sullo, Dario Cattaneo, Marta Gentili, Renata Rizzo, Antonio Pascotto, Elisa Mani, Laura Villa, Maria Pia Riccio, Serena Sperandeo, Renato Bernardini, Carmela Bravaccio, Emilio Clementi, Massimo Molteni, Francesco Rossi, Sonia Radice, Annalisa Capuano
Expert Opinion on Drug Safety, 2016
Objective: Gap in knowledge on benefit/risk ratio of second generation antipsychotics (SGA) in the paediatric population represents a challenge for the scientific community. This study aims to analyse all suspected adverse drug reactions (ADRs) to SGA observed during the study period; compare the safety profiles of risperidone and aripiprazole; evaluate the effect of switching from risperidone to aripiprazole or to a first generation antipsychotic (FGA). Methods: Prospective analysis of spontaneously reported ADRs concerning 184 paediatric outpatients between 2012 and 2014.; clinical outcomes of drug switch were evaluated. Results: Out of the 184 patients, 130 experienced at least one ADR; ADRs were usually not serious and more frequently associated with aripiprazole. Switching to aripiprazole was associated with better results than switching to FGAs in the Clinical Global Impression scale- Efficacy (CGI-E) scores (p = 0.018), Disturbed behaviour checklist-parents (DBC-P) self-absorption subscale (p = 0.010); only a trend for difference between changing to aripiprazole vs FGAs in the DBC-P total score (p = 0.054) and social relating subscale (p = 0.053) was observed. Conclusions: SGAs safety data were consistent with the ones already known; however, there is still a need to improve the knowledge in pharmacovigilance field among clinicians. Switching to aripiprazole may be a valid alternative to risperidone.
Restless sleep in a hyperactive girl a paradoxical adverse reaction to methylphenidate
Marco Pozzi, Silvana Bertella, Massimo Molteni, Stefania Antoniazzi, Carla Carnovale, Marta Gentili, Paolo Pellegrino, Valentina Perrone, Emilio Clementi, Sonia Radice
Journal of Clinical Psychopharmacology, 2015
To the Editors: M ethylphenidate (MPH) has been in clinical use for more than 50 years and extensive information is available regarding its effects on inattention and hyperactivity. Several patients with these diurnal symptoms also suffer from the following sleep impairments of variable severity: delayed sleep onset, delayed rapid eye movement phase, early awakening, and complex abnormalities involving the structure of sleep and body activity during sleep. Stimulant and nonstimulant drugs used for hyperactivity can improve sleep disturbances. Drug-induced impairments of sleep are often negligible or impact moderately on the onset and length of sleep, whereas sleep architecture is preserved. Reports of adverse drug reactions (ADRs) leading to relevant sleep alterations are infrequent and involve single symptoms, such as bruxism and hallucinations. Herein, we report a case of a 10-year-old hyperactive girl developing a complex disturbance of sleep and movement possibly due to MPH, not previously described and with possible dose dependency.
On the Possible Relationship between Anti-Streptolysin-O Titer and Neuropsychiatric Disorders Other than PANS
Marco Pozzi, Simone Pisano, Silvana Bertella, Paola Lombardi, Paolo Pellegrino, Massimo Molteni, Emilio Clementi, Carmela Bravaccio, Sonia Radice
Journal of Child and Adolescent Psychopharmacology, 2015
[Author Affiliation]Marco Pozzi. 1 Istituto Di Ricovero e Cura a Carattere Scientifico ( IRCCS) Eugenio Medea, Lecco, Italy.Simone Pisano. 2 Department of Medicine and Public Health, Second University of Naples, Naples, Italy.Silvana Bertella. 1 Istituto Di Ricovero e Cura a Carattere Scientifico ( IRCCS) Eugenio Medea, Lecco, Italy.Paola Lombardi. 2 Department of Medicine and Public Health, Second University of Naples, Naples, Italy.Paolo Pellegrino. 3 Unit of Clinical Pharmacology, Department of Biomedical and Clinical Sciences L. Sacco, "Luigi Sacco" University Hospital, Universita di Milano, Milan, Italy.Massimo Molteni. 1 Istituto Di Ricovero e Cura a Carattere Scientifico ( IRCCS) Eugenio Medea, Lecco, Italy.Emilio Clementi. 1 Istituto Di Ricovero e Cura a Carattere Scientifico ( IRCCS) Eugenio Medea, Lecco, Italy. 4 Unit of Clinical Pharmacology, National Research Council ( CNR) Institute of Neuroscience, Department of Biomedical and Clinical Sciences L. Sacco, "Luigi Sacco" University Hospital, Universita di Milano, Milan, Italy.Carmela Bravaccio. 5 Department of Translational Medical Sciences, University Federico II of Naples, Naples, Italy.Sonia Radice. 3 Unit of Clinical Pharmacology, Department of Biomedical and Clinical Sciences L. Sacco, "Luigi Sacco" University Hospital, Universita di Milano, Milan, Italy.* The first two authors contributed equally.Funding: This work was supported by Agenzia Italiana del Farmaco (AIFA) and by the Italian Ministry of Health (Ricerca Corrente 2015, to E.C.). The funding public institutions had no role in any part of the work.Address correspondence to: Emilio Clementi, PhD, Department of Biomedical and Clinical Sciences, University of Milano, Via GB Grassi 74, 20157 Milano, Italy, E-mail: emilio.clementi@unimi.itTo The Editor:Renewed interest in the relationship between autoimmune diseases and psychiatric disorders has been raised by a recent consensus paper describing pediatric acute-onset neuropsychiatric syndrome (PANS) (Chang et al. 2014), which also includes the previously known pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS) (Swedo et al. 1998). Although the diagnostic process is still debated and differential diagnosis may be challenging, several features of both disorders have been described. PANDAS is characterized by an infection-mediated (by group A-β hemolytic Streptococcus) abrupt, dramatic onset of neuropsychiatric symptoms mainly including, but not limited to, tics and obsessive-compulsive behaviors, whereas PANS may be caused by several triggers, not only postinfectious ones, and may present, together with obsessive-compulsive behaviors, with the predominant feature of acute-onset food refusal, rather than tics (Murphy et al. 2014). Anti-streptolysin O (ASO) titration is supportive of the diagnosis of PANDAS or PANS, and should be performed when they are suspected (Kiessling et al. 1993; Murphy et al. 2015; Pozzi et al. 2014). In the case of isolated measurements, the diagnostic threshold has been set at 400 U/mL, whereas the normality threshold is generally 200 U/mL, although it may be adjusted by age (Chang et al. 2014). It is also known that elevated ASO titers may be linked with a plurality of conditions that are not always pathological; however, scant data are available on the possible association of group A Streptococcus and ASO titers with the occurrence of neuropsychiatric manifestations other than Sydenham's chorea and PANDAS or PANS (Pozzi et al. 2014).Autoimmunity-based etiological hypotheses are increasingly being probed for neuropsychiatric diseases, such as autism spectrum disorders (ASD) (Keil et al. 2010). We have explored the distribution of ASO titers in a wide pediatric neuropsychiatric population, aiming to check for differences among groups of patients with different psychiatric diagnoses. …
The importance of monitoring adverse drug reactions in pediatric patients: The results of a national surveillance program in Italy
Carla Carnovale, Tatiana Brusadelli, GianVincenzo Zuccotti, Silvia Beretta, Maria Giuseppa Sullo, Annalisa Capuano, Francesco Rossi, Martina Moschini, Alessandro Mugelli, Alfredo Vannacci, Marcella Laterza, Emilio Clementi, Sonia Radice, and
Expert Opinion on Drug Safety, 2014
Objective: To gain information on safety of drugs used in pediatrics through a 4-year post-marketing active pharmacovigilance program. The program sampled the Italian population and was termed ‘Monitoring of the Adverse Effects in Pediatric population’ (MEAP). Research design and methods: Adverse drug reactions (ADRs) were collected for individuals aged 0 – 17 years treated in hospitals and territorial health services in Lombardy, Tuscany, Apulia and Campania; located to gain an appropriate sampling of the population. ADRs were evaluated using the Adverse Drug Reaction Probability Scale (Naranjo) and analyzed with respect to time, age, sex, category of ADR, seriousness, suspected medicines, type of reporter and off-label use. Results: We collected and analyzed reports from 3539 ADRs. Vaccines, antineoplastic and psychotropic drugs were the most frequently pharmacotherapeutic subgroups involved. Seventeen percent of reported ADRs were serious; of them fever, vomiting and angioedema were the most frequently reported. Eight percent of ADRs were associated with off-label use, and 10% were unknown ADRs. Analysis of these revealed possible strategies of therapy optimization. Conclusions: The MEAP project demonstrated that active post-marketing pharmacovigilance programs are a valid strategy to increase awareness on pediatric pharmacology, reduce underreporting and provide information on drug actions in pediatrics. This information enhances drug therapy optimization in the pediatric patients.
Are non-serious adverse reactions to psychiatric drugs really non-serious?
Marco Pozzi, Silvana Bertella, Dario Cattaneo, Massimo Molteni, Valentina Perrone, Carla Carnovale, Stefania Antoniazzi, Emilio Clementi, Sonia Radice
Journal of Child and Adolescent Psychopharmacology, 2013
Modulation by muscarinic antagonists of the response to carbon dioxide challenge in panic disorder
Marco Battaglia, Silvana Bertella, Anna Ogliari, Laura Bellodi, Enrico Smeraldi
Archives of General Psychiatry, 2001
A psychometric-genetic study of schizotypal disorder
M Battaglia
Schizophrenia Research, 1999
First-cycle REM density in never-depressed subjects with borderline personality disorder
Marco Battaglia, Luigi Ferini Strambi, Silvana Bertella, Sonia Bajo, Laura Bellodi
Biological Psychiatry, 1999
Assessment of parent-of-origin effect in families unlineally affected with panic disorder-agoraphobia
M Battaglia, S Bertella, S Bajo, F Binaghi, A Ogliari, L Bellodi
Journal of Psychiatric Research, 1999
An investigation of the co-occurrence of panic and somatization disorders through temperamental variables
Marco Battaglia, Silvana Bertella, Sonia Bajo, Ernestina Politi, Laura Bellodi
Psychosomatic Medicine, 1998
Anticipation of age at onset in panic disorder
Marco Battaglia, Silvana Bertella, Sonia Bajo, Flora Binaghi, Laura Bellodi
American Journal of Psychiatry, 1998
Cyclic alternating pattern of sleep electroencephalogram in patients with panic disorder
Luigi Ferini-Strambi, Laura Bellodi, Alessandro Oldani, Silvana Bertella, Salvatore Smirne, Marco Battaglia
Biological Psychiatry, 1996
Comorbidity of panic and somatization disorder: A genetic-epidemiological approach
Marco Battaglia, Luana Bernardeschi, Ernestina Politi, Silvana Bertella, Laura Bellodi
Comprehensive Psychiatry, 1995
Age at onset of panic disorder: Influence of familial liability to the disease and of childhood separation anxiety disorder
M. Battaglia, S. Bertella, E. Politi, L. Bernardeschi, G. Perna, A. Gabriele, L. Bellodi
American Journal of Psychiatry, 1995