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<dc:title>Effetti del Metilfenidato sulla crescita in bambini e adolescenti ADHD.&#xd;
Revisione sistematica e monitoraggio prospettico a lungo termine dei parametri auxologici: analisi preliminari dei risultati dello studio europeo di farmacovigilanza ADDUCE</dc:title>
<dc:creator>CARUCCI, SARA</dc:creator>
<dc:subject>ADHD</dc:subject>
<dc:subject>bon age</dc:subject>
<dc:subject>crescita</dc:subject>
<dc:subject>età ossea</dc:subject>
<dc:subject>growth</dc:subject>
<dc:subject>maturazione puberale</dc:subject>
<dc:subject>methylphenidate</dc:subject>
<dc:subject>metilfenidato</dc:subject>
<dc:subject>pubertal maturation</dc:subject>
<dc:subject>Settore BIO/14 - Farmacologia</dc:subject>
<dc:description>Stimulant medications represent the main effective treatment in improving the core symptoms of&#xd;
ADHD. However, in the last 30 years, there has been increasing concern about the risks&#xd;
associated with these medications in particular with respect to possible growth deficits, due to their&#xd;
impact on weight, height and BMI. The aim of this work was to provide an extensive update of the&#xd;
literature on methylphenidate (MPH) long-term adverse effects on growth and pubertal maturation&#xd;
in ADHD and to evaluate, within the prospective pharmaco-vigilance EU funded ADDUCE (ADHD&#xd;
DRUGS USE CHRONIC EFFECTS) study, whether MPH for ADHD is associated with a&#xd;
statistically and clinically significant increase in long-term (> 1 year) risk of negative effects on the&#xd;
rate of growth velocity and on bone and pubertal maturation and to explore the application of the&#xd;
monitoring of bone age as a helpful tool able to add value to the routine measures of growth within&#xd;
the clinical care.&#xd;
The systematic review included a Pubmed and a centralized search carried out up to July 2015,&#xd;
using Ovid Medline, Embase and PsychInfo. The review was centred on human studies focusing&#xd;
on the impact of MPH exposure on growth in ADHD children and adolescents diagnosed according&#xd;
to DSM criteria. In total 38 eligible studies were identified covering a total of 6385 subjects.&#xd;
Analysis of the impact of MPH was performed in 3790 subjects. Nineteen studies did not support&#xd;
the hypothesis of a correlation between a growth deficit and treatment. Nineteen studies (n =2018&#xd;
subjects) found instead significant changes on height, weight and BMI z scores. Height deficit&#xd;
appeared more evident during the first 6-12 months with a subsequent normalization. Dose, drug&#xd;
holidays, the length of treatment and the basal growth parameter appeared as possible important&#xd;
mediating factors.&#xd;
Within the multicentre ADDUCE longitudinal study, a total of 1397 subjects have been enrolled in&#xd;
the four countries involved into the projects (Italy, Germany, Hungary and UK). For the purpose of&#xd;
the present work, growth parameters were analysed for 267 Italian children and adolescents (129&#xd;
drug naïve ADHD starting MPH for the first time; 113 unmedicated ADHD and 25 non ADHD),&#xd;
aged 6 to 17 years old. Weight, height and BMI, their Z-scores and pubertal maturation were&#xd;
assessed at baseline and every six months within 24 months of follow up. Height velocity and the&#xd;
SDS for height velocity were calculated at 12 and 24 months. Bone age by the X-ray of left wrist&#xd;
was further assessed for 44 drug naïve ADHD children, aged 6-12, at three time points of the&#xd;
ADDUCE longitudinal protocol, baseline visit and after 12 and 24 months. Baseline data analysis&#xd;
revealed normal growth parameters for the ADHD population with height, weight and BMI Z-score&#xd;
within the expected growth national norms. At the 12 and 24 month observation, absolute values of&#xd;
height and weight continued to increase in all subjects. Medication did not cause any significant&#xd;
impact on height neither on pubertal maturation. BMI Z-score decreased significantly only during&#xd;
the first 12 month of treatment (p=.04). Growth velocity SDS at T12 was not significantly different&#xd;
when compared to T24. The calculation of the predicted adult height by using the bone age&#xd;
confirmed no suppressive effect of stimulants on height remaining substantially similar at the&#xd;
different time-points of follow up (T0= 178.37 ±7.2; T12=177.18±7.8; T24=178.63±8.0).&#xd;
In conclusion, results from the present work revealed that the condition of ADHD per se does not&#xd;
appear to include an altered pattern of growth and that MPH has a modest impact mainly on&#xd;
weight and only a marginal effect on height with a minimal clinical influence generally remittent in&#xd;
adulthood. On the bases of the present evidences is however considered appropriate to refer to&#xd;
the current clinical guidelines for an adequate drug monitoring of growth and pubertal parameters&#xd;
in children on stimulant medication.</dc:description>
<dc:date>2016-03-08</dc:date>
<dc:type>info:eu-repo/semantics/doctoralThesis</dc:type>
<dc:identifier>http://hdl.handle.net/11584/266887</dc:identifier>
<dc:language>ita</dc:language>
<dc:relation>numberofpages:170</dc:relation>
<dc:rights>info:eu-repo/semantics/openAccess</dc:rights>
<dc:publisher>Università degli Studi di Cagliari</dc:publisher>
<dc:rights>license:Non specificato</dc:rights>
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