Polanczyk 2007.

Methods	A pharmacogenomic study of children and adolescents consecutively evaluated during 2 years in the ADHD outpatient clinic
Participants	Number of participants screened: 457 Number of participants included: 137 Number of participants followed up: 106 Number of withdrawals: 31 Diagnosis of ADHD: DSM‐IV (subtype: combined (58.5%), hyperactive‐impulsive (5.7%), inattentive (26.4%)) Age: mean 10.3 years old (range: not stated) IQ: mean: 100.4 Sex: 82 males, 24 females Methylphenidate‐naïve: 100% Ethnicity: European‐Brazilian (100%) Country: Brazil Comorbidity: conduct disorder (16.0%), oppositional defiant disorder (51.9%), mood disorder (9.4%), anxiety disorder (23.6%) Comedication: yes (9.4%) Sociodemographics: not stated Inclusion criteria: ADHD diagnosis according to DSM‐IV criteria (children who fulfilled all criteria except for age of onset of impairment (i.e. before 7 years) were included) Age between 4 and 17 years, European‐Brazilian race/ethnicity Drug naïve for methylphenidate Prescribed daily dosage of methylphenidate hydrochloride of ≥ 0.3 mg/kg Data on response to methylphenidate was available for at least the first month of treatment Exclusion criteria: Not stated
Interventions	Methylphenidate type: immediate release Mean methylphenidate dosage: 0.5 mg/kg (baseline) and 0.65 mg/kg at 1 month Administration schedule: 8 am and 12 pm, with extra dose at 5‐6 pm for those needing evening coverage. Dosages of short‐acting methylphenidate were augmented until no further clinical improvement was detected or until there were limited adverse effects Duration of intervention: 3 months (1 month for 106 participants, 3 months for 89) Treatment compliance: data were excluded from 2 children because of irregular use of methylphenidate
Outcomes	Barkley Side Effect Rating Scale measured by child psychiatrists at baseline,1 and 3 months. Data not reported
Notes	Sample calculation: no Ethics approval: yes Funding/vested interests: the ADHD program received research support from the pharmaceutical companies: Bristol Myers‐Squibb, Eli Lilly and Company, Janssen‐Cilag, and Novartis Pharmaceuticals. The study was supported by grant 471761/03‐6 from Conselho Nacional de Desenvolvimento Cientıfico e Tecnologico, Programa de Apoio a Núcleos de Excelência, and Hospital de Clínicas de Porto Alegre Key conclusions of the study authors: the study documented the effect of the G allele at the ADRA2A ‐1291 C > G polymorphism on the improvement of inattentive symptoms with methylphenidate treatment in children and adolescents with ADHD. Our findings provide clinical evidence for the involvement of the noradrenergic system in the modulation of methylphenidate action Comments from the study authors: regarding adverse events, a mixed‐effects model analysis demonstrated effects of treatment over time on the Barkley Side Effect Rating Scale scores, as expected (n = 106; F2,201.2=5.4; P=.005). However, neither an effect for the presence of the G allele (n = 106; F1,107.6=0.15; P=.69) nor an interaction effect between the presence of the G allele and treatment over time (n = 106; F2,201.2=0.71; P=.49) on the Barkley Side Effect Rating Scale scores was found during the 3 months of methylphenidate use Comments from the review authors: no data presented on side effects apart from the paragraph above Exclusion of methylphenidate non‐responders/children who have previously experienced adverse events on methylphenidate: not stated