Limitations of this study include unmeasured confounding variables due to the nonrandomized design, that methylphenidate users (n=43,999) were more likely to have preexisting cardiovascular disease than nonusers (n=175,955), and limited duration of follow-up with a median of 60 days. 17 Methylphenidate dosage was inversely associated with risk, suggesting that the association may not be directly causal. found a 1.8-fold increase in risk of sudden death or ventricular arrhythmia in adult patients who initiated methylphenidate therapy. The observed effects of stimulants on BP and HR would be expected to increase cardiovascular risk. In addition, the studies were not powered due to inadequate sample size or follow-up duration to determine risk of clinical cardiovascular events. 13,14 The aforementioned studies excluded subjects with clinically significant chronic medical conditions or did not offer description of comorbidities, such as cardiovascular disease. 12 Nonetheless, it is has been shown to have similar increases in BP and HR with short term use compared to stimulants. 8-11 The nonstimulant medication, atomoxetine is a selective norepinephrine reuptake inhibitor indicated for ADHD which appears to be free of effects on other noradrenergic receptors and neurotransmitter systems. Studies have indicated small, but statistically significant increases in BP (1-6 mmHg) and HR (2-5 bpm) with short-term stimulant use, as well as similar findings with once-daily methylphenidate up to one year of use. An increase in circulating catecholamines can activate cardiovascular beta-1 adrenoreceptors resulting in increased inotropy and HR, while activation of alpha-adrenoreceptors causes vasoconstriction and a rise in BP. *Not included in the 2011 FDA Safety CommunicationĬNS stimulants exert their action on the brainstem ascending arousal system and cortex, blocking the reuptake of norepinephrine and dopamine into the presynaptic neuron and increasing their release into the extraneuronal space. Stimulant-like (non-amphetamine containing)Įxcessive sleepiness associated with narcolepsy, OSA, SWD Table 1: Stimulant and Stimulant-like MedicationsĬoncerta, Daytrana, Metadate CD, Metadate ER, Ritalin, Ritalin-LA, Ritalin-SR, Methylin, Methylin ER, Quillivant XRĭexedrin, Dexedrin Spansules, Dextrostat, Liquadd, ProCentra, Zenzedi In an effort to elucidate risk, interpretation of current evidence surrounding stimulant and stimulant-like drugs is offered. Specifically, the use of stimulants in patients with history of or susceptible to arrhythmias has not been studied. Debate remains on the safety of stimulants in the cardiovascular population. 7 Table 1 summarizes the available stimulant and stimulant-like medications, including those referenced by the FDA. 4-6 Furthermore, the FDA issued a safety announcement in 2011 stating that stimulant products and atomoxetine should not be used in patients with serious heart problems, or for whom an increase in blood pressure (BP) or heart rate (HR) would be problematic. 2,3ĭue to reports of cardiovascular adverse events and observed physiological effects, the package inserts for stimulant drugs warn against use in patients with preexisting heart disease or cardiac structural abnormalities due to risk of sudden death, stroke, and myocardial infarction (MI). Of note, OSA and other forms of sleep-disordered breathing have unfavorable effects on cardiovascular physiology, predisposing affected individuals to cardiovascular disease and cardiac arrhythmias. Such conditions are frequently associated with history or risk of cardiovascular disease. 1 Off-label treatment for conditions including weight management, fatigue related to depression, stroke, traumatic brain injury, or hyper-somnolence due to Obstructive Sleep Apnea (OSA) may account for the high prevalence of stimulant use in adults. However adults receive 32% of all issued stimulant prescriptions. It is estimated that 4.4% of US adults experience some symptoms and disabilities of ADHD. First-line stimulant class medications, such as methylphenidate and amphetamine formulations are FDA approved for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) and narcolepsy.
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