Methylphenidate and risk of serious cardiovascular events in adults.
OBJECTIVE
The authors sought to determine whether use of methylphenidate in adults is associated with elevated rates of serious cardiovascular events compared with rates in nonusers.


METHODS
This was a cohort study of new users of methylphenidate based on administrative data from a five-state Medicaid database and a 14-state commercial insurance database. All new methylphenidate users with at least 180 days of prior enrollment were identified. Users were matched on data source, state, sex, and age to as many as four comparison subjects who did not use methylphenidate, amphetamines, or atomoxetine. A total of 43,999 new methylphenidate users were identified and matched to 175,955 nonusers. Events of primary interest were 1) sudden death or ventricular arrhythmia, 2) stroke, 3) myocardial infarction, and 4) a composite endpoint of stroke or myocardial infarction.


RESULTS
The age-standardized incidence rate per 1,000 person-years of sudden death or ventricular arrhythmia was 2.17 (95% CI=1.63-2.83) in methylphenidate users and 0.98 (95% CI=0.89-1.08) in nonusers, for an adjusted hazard ratio of 1.84 (95% CI=1.33-2.55). Dosage was inversely associated with risk. Adjusted hazard ratios for stroke, myocardial infarction, and the composite endpoint of stroke or myocardial infarction did not differ statistically from 1.


CONCLUSIONS
Although initiation of methylphenidate was associated with a 1.8-fold increase in risk of sudden death or ventricular arrhythmia, the lack of a dose-response relationship suggests that this association may not be a causal one.
Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, USA.
Hedi
H
Schelleman
Warren B
WB
Bilker
Stephen E
SE
Kimmel
Gregory W
GW
Daniel
Craig
C
Newcomb
James P
JP
Guevara
Mark J
MJ
Cziraky
Brian L
BL
Strom
Sean
S
Hennessy
D000328:Adult; D000368:Aged; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000009:adverse effects; D015331:Cohort Studies; D016208:Databases, Factual; D016757:Death, Sudden, Cardiac / Q000453:epidemiology / Q000209:etiology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D001523:Mental Disorders / Q000188:drug therapy; D008774:Methylphenidate / Q000008:administration & dosage / Q000009:adverse effects*; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology / Q000209:etiology; D016016:Proportional Hazards Models; D012107:Research Design; D018570:Risk Assessment; D020521:Stroke / Q000453:epidemiology / Q000209:etiology; D014481:United States / Q000453:epidemiology; D014693:Ventricular Fibrillation / Q000453:epidemiology / Q000209:etiology
D000697:Central Nervous System Stimulants; D008774:Methylphenidate