Shin 2016.

Methods	Self‐controlled patient series analysis of cardiovascular events associated with methylphenidate treatment in children and young people with ADHD
Participants	Number of participants screened: not stated Number of participants included: 1224 Number of participants followed up: not stated Number of withdrawals: not stated Diagnosis of ADHD: ICD‐10 (subtype: not stated) Age: under 17 or 17 IQ: not stated Sex: 75‐80% males Methylphenidate‐naïve: 100% Ethnicity: not stated Country: Korea Comorbidity: the prevalence of comorbidities varied across adverse events. Depressive episode was the most common comorbidity (n = 15, 29% in participants with myocardial infarction), though only 9 (13.4%) participants with ischaemic stroke had this condition. In contrast, mental retardation occurred in 12 (18%) participants with an ischaemic stroke, while only 2 (5%) with heart failure had this condition comedication: antidepressants and antipsychotics were often co‐prescribed (15‐27%) Sociodemographics: not stated Inclusion criteria: Children and young people aged ≤ 17 years Diagnosis of ADHD (ICD‐10 (ICD, 10th revision) code F90) that had been submitted by healthcare providers from 1 January 2007 to 31 December 2011 Taking methylphenidate (ATC (Anatomical Therapeutic Chemical) code N06BA04) Had an incident cardiovascular adverse event with a recorded diagnosis during the study period New user (of MPH) with first incident cardiovascular event or symptom Exclusion criteria: None stated
Interventions	Methylphenidate type: not described Mean methylphenidate dosage: not stated Mean duration of methylphenidate exposure: 0.5 years for all events except heart failure, which was 0.3 years
Outcomes	All data used were obtained from secondary electronic records for the study participants. This study had both comparative cohort data and non‐comparative cohort data Non‐serious adverse events: These were all patients aged ≤ 17 years who had at least one recorded diagnosis of ADHD (ICD‐10 code F90), had started taking methylphenidate (ATC (Anatomical Therapeutic Chemical) code N06BA04), and had an incident cardiovascular adverse event with a recorded diagnosis during the study period (1 January 2008 and 31 December 2011)
Notes	Ethics approval: this study was approved by the institutional review board of the Korea Institute of Drug Safety and Risk Management, Seoul. Obtaining informed consent from the study population was waived by the board Funding: this research received no specific grant from any funding agency in the public, commercial, or not‐for‐profit sectors. EER was supported by an NHMRC fellowship (GNT1110139). NP was supported by an NHMRC early career fellowship (GNT1035889) Vested interests: all authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous 3 years; no other relationships or activities that could appear to have influenced the submitted work Key conclusions of the study authors: our self‐controlled patient series study suggests an increased risk of cardiac events associated with methylphenidate use Comments from the study authors: methylphenidate exposure in children/young people with a diagnosis of ADHD is associated with arrhythmia and potentially with myocardial infarction in specific time periods of use. With the increased use of drugs for ADHD globally, the benefits of methylphenidate should be carefully weighed against the potential cardiovascular risks of these drugs in children and adolescents Inclusion of methylphenidate responders only or exclusion of children who have previously experienced adverse events on methylphenidate: no