title: Safety of Methylphenidate and Atomoxetine in Children with Attention-Deficit/Hyperactivity Disorder (ADHD): Data from the Italian National ADHD Registry.
abstract: OBJECTIVE
  The aim of this study was to assess the type and frequency of adverse events (AEs) in children with attention-deficit/hyperactivity disorder (ADHD) treated with methylphenidate or atomoxetine over a 5-year period in a large naturalistic study.
  
  
  METHODS
  We draw on data from the Italian ADHD Registry, a national database for postmarketing phase IV pharmacovigilance of ADHD medications across 90 centers. AEs were defined as severe or mild as per the classification of the Italian Medicines Agency. AE frequency in the two treatment groups was compared using incidence rates per 100 person-years (IR100PY) and incidence rate ratios (IRRs). Mantel-Haenszel adjusted IRRs were calculated to control for psychiatric comorbidity.
  
  
  RESULTS
  A total of 1350 and 753 participants (aged 6-18 years, mean age 10.7 ± 2.8) were treated with methylphenidate and atomoxetine, respectively, from 2007 to 2012. Ninety participants (7 %) were switched from methylphenidate to atomoxetine, and 138 (18 %) from atomoxetine to methylphenidate. Thirty-seven children treated with atomoxetine and 12 with methylphenidate had their medication withdrawn. Overall, 645 patients (26.8 %) experienced at least one mild AE (including decreased appetite and irritability, for both drugs) and 95 patients (3.9 %) experienced at least one severe AE (including severe gastrointestinal events). IR100PY were significantly higher in the atomoxetine-treated group compared with the methylphenidate-treated group for a number of mild and severe AEs and for any severe or mild AEs. After controlling for comorbidities, IRR was still significantly higher in the atomoxetine group compared with the methylphenidate group for a number of mild (decreased appetite, weight loss, abdominal pain, dyspepsia, stomach ache, irritability, mood disorder and dizziness) and severe (gastrointestinal, neuropsychiatric, and cardiovascular) AEs.
  
  
  CONCLUSIONS
  In this naturalistic study, methylphenidate had a better safety profile than atomoxetine.
authors: Developmental Brain-Behaviour Laboratory, Department of Psychology, University of Southampton, Highfield Campus, Southampton, UK. samuele.cortese@gmail.com.|New York University Child Study Center, New York, NY, USA. samuele.cortese@gmail.com.
authors: Samuele
authors: S
authors: Cortese
authors: Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanità, Italian National Institute of Health, Viale Regina Elena, 299, 00161, Rome, Italy. pietro.panei@iss.it.
authors: Pietro
authors: P
authors: Panei
authors: Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanità, Italian National Institute of Health, Viale Regina Elena, 299, 00161, Rome, Italy.
authors: Romano
authors: R
authors: Arcieri
authors: Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanità, Italian National Institute of Health, Viale Regina Elena, 299, 00161, Rome, Italy.
authors: Elena A P
authors: EA
authors: Germinario
authors: Department of Experimental Medicine, Regional Center of Pharmacosurveillance and Pharmacoepidemiology, Second University of Naples, Naples, Italy.
authors: Annalisa
authors: A
authors: Capuano
authors: Child Neuropsychiatry Unit, Department of Neuroscience and Sense Organs, Hospital Polyclinic of Bari, University Aldo Moro, Bari, Italy.
authors: Lucia
authors: L
authors: Margari
authors: Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Italian National Institute of Health, Rome, Italy.
authors: Flavia
authors: F
authors: Chiarotti
authors: Systems Medicine Department, Child Neurology and Psychiatry Unit, Tor Vergata University Hospital of Rome, Rome, Italy.
authors: Paolo
authors: P
authors: Curatolo
mesh_terms: D000293:Adolescent; D018759:Adrenergic Uptake Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D000069445:Atomoxetine Hydrochloride / Q000009:adverse effects* / Q000627:therapeutic use; D001289:Attention Deficit Disorder with Hyperactivity / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology; D000697:Central Nervous System Stimulants / Q000009:adverse effects / Q000627:therapeutic use; D002648:Child; D015897:Comorbidity; D005260:Female; D006801:Humans; D015994:Incidence; D007558:Italy / Q000453:epidemiology; D008297:Male; D008774:Methylphenidate / Q000009:adverse effects* / Q000627:therapeutic use; D011569:Psychiatric Status Rating Scales; D011619:Psychotropic Drugs / Q000009:adverse effects* / Q000627:therapeutic use; D012042:Registries; D012720:Severity of Illness Index
chemical_list: D018759:Adrenergic Uptake Inhibitors; D000697:Central Nervous System Stimulants; D011619:Psychotropic Drugs; D008774:Methylphenidate; D000069445:Atomoxetine Hydrochloride