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Abstract

Introduction: Attention-deficit-hyperactivity disorder (ADHD) affects a substantial portion of the global population, influencing cognitive and behavioral function. Current treatments often involve stimulant medications like amphetamines, which are controlled substances due to their addiction potential. Non-stimulant options, such as atomoxetine, are typically considered secondary therapies. This study examines the relationship between ADHD medication use and the subsequent development of psychoactive, stimulant, and cocaine-related substance use disorders. Methods: Using the TriNetX database, we conducted a retrospective cohort study to compare ADHD patients prescribed amphetamines to those receiving atomoxetine or no medication. Propensity score matching was employed to control for confounding variables, followed by risk analysis to evaluate odds ratios (ORs) and hazard ratios (HRs) for developing substance-related disorders across the groups. Results: ADHD patients treated with amphetamines demonstrated significantly reduced risks of developing psychoactive, stimulant, and cocaine-related substance use disorders compared to unmedicated patients and those prescribed atomoxetine. Unmedicated patients exhibited increased risks compared to amphetamine-treated patients (OR = 1.539, 1.769, 2.210; HR = 1.842, 2.118, 2.643, respectively). Similarly, the atomoxetine group showed higher risks relative to the amphetamine group (OR = 0.635, 0.523, 0.502; HR = 0.595, 0.490, 0.469, respectively). Discussion: Although stimulant misuse concerns persist, our findings suggest that amphetamines, when used under medical supervision, may mitigate the risk of developing psychoactive and substance use disorders in ADHD populations. This highlights the potential protective effect of amphetamine treatment and underscores the importance of appropriate clinical oversight in managing ADHD.

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