title: ADHD medications and risk of serious cardiovascular events in young and middle-aged adults.
abstract: BACKGROUND
  More than 1.5 million US adults use stimulants and other medications labeled for treatment of attention-deficit/hyperactivity disorder (ADHD). These agents can increase heart rate and blood pressure, raising concerns about their cardiovascular safety.
  
  
  OBJECTIVE
  To examine whether current use of medications prescribed primarily to treat ADHD is associated with increased risk of serious cardiovascular events in young and middle-aged adults.
  
  
  METHODS
  Retrospective, population-based cohort study using electronic health care records from 4 study sites (OptumInsight Epidemiology, Tennessee Medicaid, Kaiser Permanente California, and the HMO Research Network), starting in 1986 at 1 site and ending in 2005 at all sites, with additional covariate assessment using 2007 survey data. Participants were adults aged 25 through 64 years with dispensed prescriptions for methylphenidate, amphetamine, or atomoxetine at baseline. Each medication user (n = 150,359) was matched to 2 nonusers on study site, birth year, sex, and calendar year (443,198 total users and nonusers).
  
  
  METHODS
  Serious cardiovascular events, including myocardial infarction (MI), sudden cardiac death (SCD), or stroke, with comparison between current or new users and remote users to account for potential healthy-user bias.
  
  
  RESULTS
  During 806,182 person-years of follow-up (median, 1.3 years per person), 1357 cases of MI, 296 cases of SCD, and 575 cases of stroke occurred. There were 107,322 person-years of current use (median, 0.33 years), with a crude incidence per 1000 person-years of 1.34 (95% CI, 1.14-1.57) for MI, 0.30 (95% CI, 0.20-0.42) for SCD, and 0.56 (95% CI, 0.43-0.72) for stroke. The multivariable-adjusted rate ratio (RR) of serious cardiovascular events for current use vs nonuse of ADHD medications was 0.83 (95% CI, 0.72-0.96). Among new users of ADHD medications, the adjusted RR was 0.77 (95% CI, 0.63-0.94). The adjusted RR for current use vs remote use was 1.03 (95% CI, 0.86-1.24); for new use vs remote use, the adjusted RR was 1.02 (95% CI, 0.82-1.28); the upper limit of 1.28 corresponds to an additional 0.19 events per 1000 person-years at ages 25-44 years and 0.77 events per 1000 person-years at ages 45-64 years.
  
  
  CONCLUSIONS
  Among young and middle-aged adults, current or new use of ADHD medications, compared with nonuse or remote use, was not associated with an increased risk of serious cardiovascular events. Apparent protective associations likely represent healthy-user bias.
authors.affiliation: Division of Research, Kaiser Permanente Northern California, 2000 Broadway, Fifth Floor, Oakland, CA 94612,, USA. laurel.habel@kp.org
authors.forename: Laurel A
authors.initials: LA
authors.lastname: Habel
authors.forename: William O
authors.initials: WO
authors.lastname: Cooper
authors.forename: Colin M
authors.initials: CM
authors.lastname: Sox
authors.forename: K Arnold
authors.initials: KA
authors.lastname: Chan
authors.forename: Bruce H
authors.initials: BH
authors.lastname: Fireman
authors.forename: Patrick G
authors.initials: PG
authors.lastname: Arbogast
authors.forename: T Craig
authors.initials: TC
authors.lastname: Cheetham
authors.forename: Virginia P
authors.initials: VP
authors.lastname: Quinn
authors.forename: Sascha
authors.initials: S
authors.lastname: Dublin
authors.forename: Denise M
authors.initials: DM
authors.lastname: Boudreau
authors.forename: Susan E
authors.initials: SE
authors.lastname: Andrade
authors.forename: Pamala A
authors.initials: PA
authors.lastname: Pawloski
authors.forename: Marsha A
authors.initials: MA
authors.lastname: Raebel
authors.forename: David H
authors.initials: DH
authors.lastname: Smith
authors.forename: Ninah
authors.initials: N
authors.lastname: Achacoso
authors.forename: Connie
authors.initials: C
authors.lastname: Uratsu
authors.forename: Alan S
authors.initials: AS
authors.lastname: Go
authors.forename: Steve
authors.initials: S
authors.lastname: Sidney
authors.forename: Mai N
authors.initials: MN
authors.lastname: Nguyen-Huynh
authors.forename: Wayne A
authors.initials: WA
authors.lastname: Ray
authors.forename: Joe V
authors.initials: JV
authors.lastname: Selby
mesh_terms: D000328:Adult; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy*; D002318:Cardiovascular Diseases / Q000453:epidemiology* / Q000517:prevention & control; D000697:Central Nervous System Stimulants / Q000009:adverse effects* / Q000627:therapeutic use; D015331:Cohort Studies; D016757:Death, Sudden, Cardiac / Q000453:epidemiology; D057286:Electronic Health Records; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology; D012189:Retrospective Studies; D012306:Risk; D020521:Stroke / Q000453:epidemiology
chemical_list: D000697:Central Nervous System Stimulants