Hammerness 2009.

Methods	An open‐label, prospective, long‐term study of osmotic release oral system methylphenidate for smoking prevention in adolescents with ADHD for 24 months
Participants	Number of participants screened: 203 Number of participants included: 154 Number of participants followed up: 30 Number of withdrawals: 124 Diagnosis of ADHD: DSM‐IV (subtype: not stated) Age: mean 15.3 years (range 12‐18) IQ: > 75 Sex: 114 males, 40 females Methylphenidate‐naïve: not stated Ethnicity: not stated Country: USA Comorbidity: none Comedication: not stated Sociodemographics: not stated Supplementary data from a 6 months period during the main study Number of participants screened: 152 Number of participants included: 114 Number of participants followed up: 57 Number of withdrawals: 57 Age: mean 14.1 years (range 12‐18) Sex: 83 males, 31 females Inclusion criteria Adolescent outpatients between 12 to 17 years of age Participants with the DSM‐IV diagnosis of ADHD, as manifested in the clinical evaluation and confirmed by structured interview, supplemented with structured diagnostic psychiatric interview using the Schedule for Affective Disorders and Schizophrenia for School Aged Children (KSADS‐E) Participants with sufficient current ADHD symptoms to warrant treatment, as measured by a Clinical Global Impression Severity Scale (CGI‐S) score of greater than or equal to 4 (moderately ill); OR participants already on Concerta who are judged to be responders (CGI of 1‐2) and who tolerate treatment well Exclusion criteria Any serious or unstable medical illness including hepatic, renal, gastroenterologic, respiratory, cardiovascular (including ischaemic heart disease, hypertension), endocrinologic, neurologic, immunologic, or haematologic disease Clinically significant abnormal baseline laboratory values History of seizures Active tic disorder Pregnant or nursing females Mental retardation (IQ < 75) Organic brain disorder Eating disorders, psychosis, current episode of bipolar disorder, current depression > mild (CGI‐S > 3), or current anxiety > mild (CGI‐S > 3) Substance abuse or dependence within the past 2 months Recent change in non‐monoamine oxidase inhibitor (MAOI) antidepressants (< 3 months) Recent change in benzodiazepines (< 3 months) Concerta non‐responder History of cardiovascular disease, including structural cardiac abnormalities Participants were dropped from the study if in the investigator's opinion there was lack of efficacy, intolerable adverse events, and/or clinically significant laboratory values, pregnancy, clinical worsening, or noncompliance with the study protocol
Interventions	Methylphenidate type: osmotic release oral system Mean methylphenidate dosage: 63.1 mg at week 6 and 67.2 mg after 6 months Administration schedule: morning Duration of intervention: 24 months Treatment compliance: not stated
Outcomes	Serious adverse events: Adverse events were systematically recorded at each visit. Adverse events were assessed according to a general query by the treating physician, monitoring emergent and/or ongoing subjective complaints. Adverse effects were followed to resolution There were no serious adverse events or serious cardiovascular adverse events (AEs) in the first 6 months 10 of 114 participants reported ≥ 1 cardiovascular complaint Vital signs were collected as a single, first reading, typically 7 to 10 h after morning administration of medication, during after school office visits Participants with systolic blood pressure (SBP) or diastolic BP (DBP) readings (or both) at or above the 95th percentile for sex, age and height on ≥ 3 consecutive appointments were defined as hypertensive Participants with SBP and/or DBP readings above the 90th percentile for sex, age, and height on ≥ 3 consecutive appointments were defines as prehypertensive During OROS methylphenidate treatment 8% (n = 9/114) of the sample met our defined criteria for prehypertension and 6% (n = 7/114) of the sample met criteria for hypertension It seems the denominator being used for calculation of adverse event proportions below 154 came from the 2‐year study on smoking. Incorporates 50 more participants than those studied in the present work Non‐serious adverse events Different types of adverse outcomes
Notes	Sample calculation: no Ethics approval: approved by the Massachusetts General Hospital Institutional Review board. Funding: not stated Vested interests/authors' affiliations: the authors have several affiliations to the medical industry both as researchers, speakers, consultants, etc. Key conclusions of the study authors: treatment with relatively high doses of OROS methylphenidate was associated with small but statistically significant mean increases in BP and HR, primarily during the first 6 weeks of treatment, without clinically meaningful changes in ECG. These observations are consistent with previous reports using lower doses Exclusion of methylphenidate non‐responders/children who have previously experienced adverse events on methylphenidate: yes