QT prolongation by dexamphetamine: Does experience matter?

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Amphetamines are stimulant drugs most commonly known for the treatment of attention‐deficit hyperactivity disorder (ADHD). They are also used as recreational drugs, albeit at higher dosages. Case reports of life‐threatening cardiac arrhythmias and sudden cardiac arrest (SCA) among amphetamine users have raised serious concerns about the cardiac safety of these drugs.1 Accordingly, the Food and Drug Administration issued a warning in 2006 cautioning the association of stimulant drugs for ADHD treatment with serious cardiovascular events such as SCA.3 Understanding the nature and causes of this association is clearly relevant, given that the prevalence of both ADHD4 and recreational amphetamine use5 is high and rising. Retrospective cohort studies have not confirmed that the incidence of SCA among ADHD patients treated with amphetamines is increased on average.6 Yet, case reports indicate that there are individuals with increased susceptibility to SCA, in particular, those with first‐time use of amphetamines.1 This complexity has remained unresolved, as systematic studies on the effects of amphetamines on human cardiac electrophysiologic properties have been lacking.
We aimed to shed further light on this complexity by comparing changes in electrocardiogram (ECG) parameters upon intravenous bolus administration of a single high dose of dexamphetamine (dAMPH) between habitual recreational dAMPH users and nonusers.
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