Wilens 2006.

Methods	A 2‐week randomised, double‐blind, 15‐centre, parallel trial with 2 arms: Methylphenidate osmotic release oral system (OROS) Placebo Preceded by a 4 week open‐label dose titration phase and followed by a 8 week open‐label follow‐up
Participants	Number of participants screened: not stated Number of participants included: 220 in the 4 week dose titration phase Number of participants randomised to methylphenidate: 87 and placebo: 90 Number followed up in the methylphenidate group: 71 Number of withdrawals in methylphenidate group: 16 Number followed up: 171 (total) Number completed follow‐up: 135 Diagnosis of ADHD: DSM‐IV (subtype: not stated) Age: mean: 14.6 years old (range 13‐18) IQ: not stated Sex: 142 males, 35 females Methylphenidate‐naïve: not stated, but ADHD treatment naïve (n = 24) Ethnicity: white (75.1%), African American (13.6%), others (11.3%) Country: USA Comorbidity: no Comedication: none Sociodemographics: not stated Inclusion criteria: Diagnosis of ADHD as defined by DSM‐IV Children's Global Assessment Scale rating of 41‐70 at baseline (Screening Phase) Age between 8‐13 years Exclusion criteria: Participants who are known to not respond to methylphenidate Have had adverse experiences from methylphenidate or hypersensitivity to CONCERTA or its components Have marked anxiety, tension or agitation A psychiatric co‐morbidity requiring additional or different medication Have glaucoma, ongoing seizure disorder, psychotic disorder, Tourette disorder or family history of Tourette disorder, bipolar disorder, an eating disorder Treatment with theophylline, coumarin, anticonvulsants Severe gastrointestinal narrowing Systolic or diastolic blood pressures at the 95th percentile or greater for age, sex and height at screening
Interventions	Participants were randomly assigned to OROS‐methylphenidate or placebo Mean methylphenidate dosage: 0.84 mg/kg Administration schedule: once daily Duration of intervention: 2 weeks Titration period: 4 weeks initiated before randomisation. All participants initiated therapy at 18 mg/day, and clinical response was measured after 1 week. If response to treatment was inadequate, as per the a priori study definition, the dose was titrated upward (in 18 mg increments) at 1 week intervals for up to 4 weeks, with the maximum dose being 72 mg/day Treatment compliance: not stated 8‐week open‐label follow‐up on individualised dosage
Outcomes	ADHD symptoms ADHD‐RS, clinician and parent rated, completed at baseline and weekly during double blind phase Serious adverse events Serious adverse events were reported in only 1 participant during the open‐label dose titration phase of the study. While being treated with OROS, 18 mg/daily, a 16‐year‐old female participant with a history of depression and suicidal ideation threatened suicide on the third day of medication use after an argument with her mother. A decision was made to discontinue study medication, and the symptoms resolved No serious adverse events were reported during the double‐blind phase Non‐serious adverse events Heart rate and blood pressure, recorded by a clinician weekly throughout whole study ECG at screening and at the end of the double‐blind phase of the study Spontaneous reports to the investigator of adverse events were recorded at weekly visits Safety assessments made at monthly visit and every 2 weeks between monthly visits during the follow‐up Height and weight were assessed at baseline and at weeks 4 and 8 in the follow‐up study No participants experienced clinically important effects on ECG‐indexes, heart rate or blood pressure during the study
Notes	Sample calculation: yes Ethics approval: yes, approval of the study design was obtained from the institutional review boards for all participating centres before initiation of the study Key conclusions of the study authors: in adolescents, once‐daily OROS methylphenidate significantly reduced ADHD symptoms and was well tolerated using dosages up to 72 mg/daily. Adolescents required, on average, a higher absolute dose but a lower weight‐adjusted dose (mg/kg) of OROS than was previously reported in children. The incidence of adverse events was not related to dose Comments from the study authors: participants were titrated to their individualised dosage before the double‐blind phase of the study may have biased the results toward a positive response in the double‐blind phase. The short duration of the double‐blind phase also may have decreased the likelihood of detecting potential rare adverse events. The rates of adverse events reported for OROS have been underestimated, because participants entering this study phase were already stabilised on an affective tolerated dosage of medication Supplemental information requested through email correspondence with the authors in December 2013 and January 2014. No reply