Il disturbo d'ansia generalizzato in bambini ed adolescenti: predittori di risposta al trattamento farmacologico con inibitori selettivi del re-uptake serotoninergico (SSRI).

Nella presente trattazione nell’ambito del disturbo d’ansia generalizzato (DAG) in età evolutiva, ho posto l’attenzione sul trattamento farmacologico con farmaci inibitori selettivi della ricaptazione della serotonina (SSRI), includendo una revisione sistematica della letteratura scientifica da cui emerge una buona efficacia e tollerabilità di tale classe di farmaci, con evidenze maggiori per sertralina, fluoxetina e fluvoxamina. Ho partecipato ad uno studio clinico finalizzato a valutare l’efficacia del trattamento con SSRI in pazienti con diagnosi principale di DAG, età: 7−18 anni (N=160). L’età di esordio sintomatologico, prima e dopo 12 anni, è stata ipotizzata specificatore del pattern evolutivo. Tutti i partecipanti hanno assunto monoterapia con SSRI. Dopo 3 mesi, 97 pazienti risultavano responsivi, indipendentemente dal tipo di SSRI assunto. I pazienti farmacoresistenti erano più giovani (p<.001), presentavano un esordio sintomatologico più precoce (p<.001), una compromissione clinica maggiore (p<.001), una maggior comorbidità con disturbi internalizzanti in generale (p<.001) e con il disturbo d’ansia di separazione in particolare (p=.002). La monoterapia con SSRI è efficace in circa il 60% dei pazienti in età pediatrica con diagnosi di DAG, tuttavia i soggetti più giovani, con una gravità clinica maggiore e una comorbidità multipla sono meno responsivi al trattamento

Acute Tolerability of Methylphenidate in Treatment-Naïve Children with ADHD: An Analysis of Naturalistically Collected Data from Clinical Practice

OBJECTIVES: The acute tolerability of methylphenidate (MPH) in children with attention-deficit/hyperactivity disorder (ADHD) has been studied mainly in research samples. Taking advantage of the mandatory test-dose procedure required for starting MPH in Italy, this study aimed to assess the incidence of intolerable adverse events after initial exposure to MPH in routine clinical practice. METHODS: The medical records of 480 consecutively treated, previously drug-naïve children and adolescents with ADHD (90% male, mean age 10.6 ± 3.0 years) were retrospectively analyzed. All children received an initial single dose of MPH immediate release (5 or 10 mg) followed by a 4-hour direct medical observation. Heart rate and blood pressure were measured at dosing and 1, 2, and 3 hours afterwards. If the first dose was well tolerated, the child continued treatment with MPH 5–20 mg daily, and was reassessed a week later. RESULTS: Eleven patients (2.3%, 95% CI 1.1–4.1) interrupted treatment within a week of initiation because of the following adverse events: irritability (n = 3), tics worsening (n = 3), reduced appetite (n = 1), enuresis (n = 1), hallucinations (n = 1), hyperfocus (n = 1), and ‘rebound’ behavioral worsening (n = 1). The most common adverse events were reduced appetite (20%), irritability (14.2%), headache (10.6%), sleep problems (9.4%), stomachache (9.4%), and tics (5%). Intellectual disability increased the risk of any adverse event in general and of irritability in particular. No cardiovascular symptom was clinically reported. However, routine assessments of vital signs during the first 3 hours after the first dose of MPH showed that 9% of the children had a 20% increase in heart rate, 8.8% had a 20% increase in diastolic blood pressure and 4.5% had a 20% increase in systolic blood pressure. Of these, 25.2% still had an elevated heart rate 1 week later. CONCLUSIONS: Among stimulant-naïve children in clinical practice, the incidence of acute MPH intolerance can be estimated to be between 1.2 and 4.1%. An asymptomatic elevation in cardiovascular parameters can be observed in about 1 out of 10 children and warrants monitoring during ongoing treatment

Custom CGH array profiling of copy number variations (CNVs) on chromosome 6p21.32 (HLA locus) in patients with venous malformations associated with multiple sclerosis

<p>Abstract</p> <p>Background</p> <p>Multiple sclerosis (MS) is a complex disorder thought to result from an interaction between environmental and genetic predisposing factors which have not yet been characterised, although it is known to be associated with the HLA region on 6p21.32. Recently, a picture of chronic cerebrospinal venous insufficiency (CCSVI), consequent to stenosing venous malformation of the main extra-cranial outflow routes (VM), has been described in patients affected with MS, introducing an additional phenotype with possible pathogenic significance.</p> <p>Methods</p> <p>In order to explore the presence of copy number variations (CNVs) within the HLA locus, a custom CGH array was designed to cover 7 Mb of the HLA locus region (6,899,999 bp; chr6:29,900,001-36,800,000). Genomic DNA of the 15 patients with CCSVI/VM and MS was hybridised in duplicate.</p> <p>Results</p> <p>In total, 322 CNVs, of which 225 were extragenic and 97 intragenic, were identified in 15 patients. 234 known polymorphic CNVs were detected, the majority of these being situated in non-coding or extragenic regions. The overall number of CNVs (both extra- and intragenic) showed a robust and significant correlation with the number of stenosing VMs (Spearman: r = 0.6590, p = 0.0104; linear regression analysis r = 0.6577, p = 0.0106).</p> <p>The region we analysed contains 211 known genes. By using pathway analysis focused on angiogenesis and venous development, MS, and immunity, we tentatively highlight several genes as possible susceptibility factor candidates involved in this peculiar phenotype.</p> <p>Conclusions</p> <p>The CNVs contained in the HLA locus region in patients with the novel phenotype of CCSVI/VM and MS were mapped in detail, demonstrating a significant correlation between the number of known CNVs found in the HLA region and the number of CCSVI-VMs identified in patients. Pathway analysis revealed common routes of interaction of several of the genes involved in angiogenesis and immunity contained within this region. Despite the small sample size in this pilot study, it does suggest that the number of multiple polymorphic CNVs in the HLA locus deserves further study, owing to their possible involvement in susceptibility to this novel MS/VM plus phenotype, and perhaps even other types of the disease.</p

How COVID-19 Phases Have Impacted Psychiatric Risk: A Retrospective Study in an Emergency Care Unit for Adolescents

Dramatic events during the COVID-19 pandemic have acutely impacted the psychosocial environment worldwide, with negative implications for mental health, particularly for more vulnerable children and adolescents with severe psychiatric illnesses. Some data suggest that the pandemic waves may have produced different psychopathological consequences, further worsening in the second phase of the pandemic, compared to those in the first lockdown, soon after March 2020. To test the hypothesis of a further worsening of psychiatric consequences of COVID-19 in the second lockdown compared to the first lockdown, we focused our analysis on a consecutive sample of youth referred to a psychiatric emergency unit for acute mental disorders in the time period between March 2019–March 2021. The sample, consisting of 241 subjects (123 males and 118 females, ranging in age from 11 to 17 years), was divided into three groups: Pre-Lockdown Group (PLG, 115 patients); First Lockdown Group (FLG, 65 patients); and Second Lockdown Group (SLG, 61 patients). Patients in the SLG presented more frequently with non-suicidal self-injuries (NSSIs), suicidal ideation, and suicidal behavior, while no significant differences in self-harm were found between PLG and FLG. Eating disorders were more frequent in both the FLG and SLG, compared to the PLG, while sleep problems were higher only in the SLG. Furthermore, patients in the SLG presented with more frequent psychological maltreatments and neglect, as well as with psychiatric disorders in the parents. Adverse traumatic experiences and internalizing disorders were significantly associated with an increased risk of suicidality. Intellectual disability was less represented from the PLG to SLG, and similarly, the rate of ADHD was lower in the SLG. No differences were found for the other psychiatric diagnoses. This information may be helpful for a better understanding and management of adolescents with severe emotional and behavioral disorders after the exposure to long-lasting collective traumas

Omega-3/6 supplementation for mild to moderate inattentive ADHD: a randomised, double-blind, placebo-controlled efficacy study in Italian children

Recently there has been a growing interest in non-pharmacological treatments for ADHD. We evaluated the efficacy of a specific Omega-3/6 dietary supplement (two capsules containing 279 mg eicosapentaenoic acid [EPA], 87 mg Docosahexaenoic Acid [DHA], 30 mg gamma linolenic acid [GLA] each) in ameliorating inattentive symptoms in inattentive-ADHD children (6-12 years) with a baseline ADHD-RS-Inattention score &gt;= 12. Secondary objectives included changes in global functioning, severity of illness, depression, and anxiety symptoms, learning disorders and in the fatty acids blood levels. The study was a randomised, double-blind, placebo-controlled efficacy and safety trial with a 6-month double-blind evaluation of Omega-3/6 vs placebo (Phase-I) and a further 6-month-open-label treatment with Omega-3/6 on all patients (Phase-II). In total 160 subjects were enrolled. No superiority of Omega-3/6 supplement to placebo was observed on the primary outcome (ADHD-RS-inattention score) after the first 6-months, with 46.3% of responders in the Omega-3/6 group and 45.6% in the placebo group; a slight (not statistically significant) reduction in Omega-6/3 ratio blood levels was measured in the active treatment group. Twelve months after enrolment, percentages of responders were similar between groups. A mild statistical, although not clinically significant, improvement was observed on the ADHD-RS-total score in the Omega-3/6 group but not on the ADHD-RS-Inattention score; a slight (not-statistically significant) reduction in Omega-6/3 ratio was observed in the group taking active treatment only during Phase II. In conclusion, no clinical beneficial effects of Omega-3/6 were detected on inattentive symptoms, suggesting a limited role of Omega-3/6 dietary products in children with mild ADHD-I. Trial registration: At the time of the Ethical submission, according to the clinical trial Italian law, registration was not mandatory for food additive as Omega 3/6 were then classified. The trial was approved by the Ethical Committee of the Cagliari University Hospital (resolution n. 662; September 22nd, 2011)